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acrac_69472_2

Liver Lesion Initial Characterization

hUMass Medical School, Worcester, Massachusetts. iUniversity of Florida College of Medicine, Gainesville, Florida. jRush University Medical Center, Chicago, Illinois; American College of Surgeons. kNew York University Medical Center, New York, New York. lStanford University Medical Center, Stanford, California. mUniversity of Alabama Medical Center, Birmingham, Alabama. nUniversity of Alabama Medical Center, Birmingham, Alabama. oJohns Hopkins Bayview Medical Center, Baltimore, Maryland. pUniversity of Illinois College of Medicine, Chicago, Illinois; American College of Physicians. qJohns Hopkins Hospital, Baltimore, Maryland. rSpecialty Chair, Virginia Commonwealth University Medical Center, Richmond, Virginia. Reprint requests to: [email protected] Liver Lesion-Initial Characterization For MRI, extracellular gadolinium-based contrast agents are commonly used in a variety of clinical settings. However, hepatobiliary contrast agents were developed to assist with detection and characterization of liver lesions. Two such agents are available: gadoxetate disodium and gadobenate dimeglumine. Hepatobiliary agents have the advantage of hepatobiliary phase (HBP) in addition to the dynamic postcontrast phases. In the HBP, parenchymal uptake of the contrast agent provides avid enhancement of the liver and therefore the ability to detect nonhepatocellular lesions. Of the two agents, gadoxetate is used more widely for HBP imaging as its HBP occurs approximately 20 minutes after injection as compared with 1 to 2 hours when using gadobenate. A positron-emitting radioisotope-labeled somatostatin analogue called Ga-68-DOTATATE utilized in PET/CT is designed to image neuroendocrine tumors (NETs). It offers a higher spatial resolution and considerably shorter imaging times compared with In-111 somatostatin receptor or metaiodobenzylguanidine scintigraphy [8]. Discussion of Procedures by Variant Variant 1: Indeterminate, greater than 1 cm liver lesion on initial imaging with US.

Liver Lesion Initial Characterization. hUMass Medical School, Worcester, Massachusetts. iUniversity of Florida College of Medicine, Gainesville, Florida. jRush University Medical Center, Chicago, Illinois; American College of Surgeons. kNew York University Medical Center, New York, New York. lStanford University Medical Center, Stanford, California. mUniversity of Alabama Medical Center, Birmingham, Alabama. nUniversity of Alabama Medical Center, Birmingham, Alabama. oJohns Hopkins Bayview Medical Center, Baltimore, Maryland. pUniversity of Illinois College of Medicine, Chicago, Illinois; American College of Physicians. qJohns Hopkins Hospital, Baltimore, Maryland. rSpecialty Chair, Virginia Commonwealth University Medical Center, Richmond, Virginia. Reprint requests to: [email protected] Liver Lesion-Initial Characterization For MRI, extracellular gadolinium-based contrast agents are commonly used in a variety of clinical settings. However, hepatobiliary contrast agents were developed to assist with detection and characterization of liver lesions. Two such agents are available: gadoxetate disodium and gadobenate dimeglumine. Hepatobiliary agents have the advantage of hepatobiliary phase (HBP) in addition to the dynamic postcontrast phases. In the HBP, parenchymal uptake of the contrast agent provides avid enhancement of the liver and therefore the ability to detect nonhepatocellular lesions. Of the two agents, gadoxetate is used more widely for HBP imaging as its HBP occurs approximately 20 minutes after injection as compared with 1 to 2 hours when using gadobenate. A positron-emitting radioisotope-labeled somatostatin analogue called Ga-68-DOTATATE utilized in PET/CT is designed to image neuroendocrine tumors (NETs). It offers a higher spatial resolution and considerably shorter imaging times compared with In-111 somatostatin receptor or metaiodobenzylguanidine scintigraphy [8]. Discussion of Procedures by Variant Variant 1: Indeterminate, greater than 1 cm liver lesion on initial imaging with US.

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acrac_69472_3

Liver Lesion Initial Characterization

Normal liver. No suspicion or evidence of extrahepatic malignancy or underlying liver disease. CT Abdomen In some cases, establishing the benign nature of the lesion, rather than a definitive diagnosis is sufficient. In differentiation between malignant and benign lesions, contrast-enhanced CT is accurate in 74% to 95% of cases [9,10]. Definitive diagnosis can be established on contrast-enhanced CT in 71% of patients, with additional imaging recommended in 10% of patients [11]. For patients with incidental liver lesions, multiphase contrast-enhanced CT has 91% to 95% accuracy for diagnosis of hemangioma, 85% to 93% accuracy for the diagnosis of FNH, and 96% to 99% accuracy for diagnosis of HCC [10,12]. For lesions detected on grayscale US, contrast-enhanced CT has sensitivity of 72% to 91%, specificity of 38% to 82%, positive predictive value (PPV) of 92%, negative predictive value (NPV) of 80%, and accuracy of 80% to 88% for establishing a definitive diagnosis [9,13]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT in this clinical scenario. DOTATATE PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of Ga-68-DOTATATE PET/CT in this clinical scenario. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen There is no relevant literature to support the use of In-111 somatostatin receptor scan with single-photon emission computed tomography (SPECT) or SPECT/CT in this clinical scenario. MRI Abdomen In lesions detected on grayscale US, one study of MRI with and without intravenous (IV) contrast has sensitivity of 82% and specificity of 43% for establishing an exact diagnosis [14].

Liver Lesion Initial Characterization. Normal liver. No suspicion or evidence of extrahepatic malignancy or underlying liver disease. CT Abdomen In some cases, establishing the benign nature of the lesion, rather than a definitive diagnosis is sufficient. In differentiation between malignant and benign lesions, contrast-enhanced CT is accurate in 74% to 95% of cases [9,10]. Definitive diagnosis can be established on contrast-enhanced CT in 71% of patients, with additional imaging recommended in 10% of patients [11]. For patients with incidental liver lesions, multiphase contrast-enhanced CT has 91% to 95% accuracy for diagnosis of hemangioma, 85% to 93% accuracy for the diagnosis of FNH, and 96% to 99% accuracy for diagnosis of HCC [10,12]. For lesions detected on grayscale US, contrast-enhanced CT has sensitivity of 72% to 91%, specificity of 38% to 82%, positive predictive value (PPV) of 92%, negative predictive value (NPV) of 80%, and accuracy of 80% to 88% for establishing a definitive diagnosis [9,13]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT in this clinical scenario. DOTATATE PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of Ga-68-DOTATATE PET/CT in this clinical scenario. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen There is no relevant literature to support the use of In-111 somatostatin receptor scan with single-photon emission computed tomography (SPECT) or SPECT/CT in this clinical scenario. MRI Abdomen In lesions detected on grayscale US, one study of MRI with and without intravenous (IV) contrast has sensitivity of 82% and specificity of 43% for establishing an exact diagnosis [14].

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acrac_69472_4

Liver Lesion Initial Characterization

In another series, MRI with and without IV contrast is able to establish a definitive diagnosis in 95% of liver lesions, which is significantly higher than contrast- enhanced CT [11]. Furthermore, only 1.5% of patients with MRIs require recommendation for further imaging as opposed to 10% with CT [11]. Performance characteristics of MRI depend on the sequences and type of contrast, as well as the lesion itself. A combination of diffusion-weighted imaging (DWI) and HBP allows correct classification of lesions as benign or malignant in 91% of cases and exact characterization in 85% of cases [15]. Gadoxetate-enhanced MRI has an accuracy of 95% to 99% for diagnosis of hemangioma, accuracy of 88% to 99% for the diagnosis of FNH, and accuracy of 97% for diagnosis of HCC in patients with incidentally discovered liver lesions [10,12]. For differentiation between adenoma and FNH, low signal on HBP is 100% specific, 92% sensitive, Liver Lesion-Initial Characterization and 97% accurate for hepatocellular adenoma [16]. However, it should be noted that inflammatory adenoma can mimic FNH on MRI [17]. For the diagnosis of a hemangioma, MRI with extracellular gadolinium contrast has sensitivity of 93%, specificity of 99%, accuracy of 98%, PPV of 96%, and NPV of 99% [18]. Although apparent diffusion coefficient (ADC) values of solid benign lesions are higher than those of the solid malignant lesions, there is a considerable overlap of the ADC values between the two groups [19]. Therefore, in patients without a history of malignancy, the value of DWI for differentiating solid liver masses may be limited. There is no relevant literature that has assessed the performance of MRI without IV contrast specifically for this clinical scenario. Therefore, the committee recommendations on the use of MRI without IV contrast are based primarily on expert opinion.

Liver Lesion Initial Characterization. In another series, MRI with and without IV contrast is able to establish a definitive diagnosis in 95% of liver lesions, which is significantly higher than contrast- enhanced CT [11]. Furthermore, only 1.5% of patients with MRIs require recommendation for further imaging as opposed to 10% with CT [11]. Performance characteristics of MRI depend on the sequences and type of contrast, as well as the lesion itself. A combination of diffusion-weighted imaging (DWI) and HBP allows correct classification of lesions as benign or malignant in 91% of cases and exact characterization in 85% of cases [15]. Gadoxetate-enhanced MRI has an accuracy of 95% to 99% for diagnosis of hemangioma, accuracy of 88% to 99% for the diagnosis of FNH, and accuracy of 97% for diagnosis of HCC in patients with incidentally discovered liver lesions [10,12]. For differentiation between adenoma and FNH, low signal on HBP is 100% specific, 92% sensitive, Liver Lesion-Initial Characterization and 97% accurate for hepatocellular adenoma [16]. However, it should be noted that inflammatory adenoma can mimic FNH on MRI [17]. For the diagnosis of a hemangioma, MRI with extracellular gadolinium contrast has sensitivity of 93%, specificity of 99%, accuracy of 98%, PPV of 96%, and NPV of 99% [18]. Although apparent diffusion coefficient (ADC) values of solid benign lesions are higher than those of the solid malignant lesions, there is a considerable overlap of the ADC values between the two groups [19]. Therefore, in patients without a history of malignancy, the value of DWI for differentiating solid liver masses may be limited. There is no relevant literature that has assessed the performance of MRI without IV contrast specifically for this clinical scenario. Therefore, the committee recommendations on the use of MRI without IV contrast are based primarily on expert opinion.

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acrac_69472_5

Liver Lesion Initial Characterization

In some cases, MRI without IV contrast may be appropriate, particularly if the initial US has a high index of suspicion for the diagnosis of a cyst. Image-Guided Biopsy Liver An indeterminate liver lesion detected on US is often further evaluated with a diagnostic CT or MRI prior to biopsy, in order to avoid biopsy of solid benign liver lesions such as hemangiomas or areas of FNH [4]. Percutaneous image-guided biopsy may be necessary to establish the diagnosis, particularly when the imaging features on a CT or MRI examination indicate possibility of malignancy. In some liver lesions, such as lymphoma, histopathologic analysis is the only technique that can make a definitive diagnosis [20]. Various techniques exist for guidance of the biopsy, and US and CT are the most commonly utilized modalities for biopsy guidance. When a biopsy is performed to diagnose or rule out malignancy in indeterminate lesions, the overall technical success rate under grayscale US guidance is 74%, which can be increased to 100% under CEUS guidance [21,22]. The percentage of tumor cells in the biopsy sample is greater with a higher number of collected biopsy samples [23]. Furthermore, for lesions not seen on grayscale US, the success rate for CEUS-guided biopsy can be as high as 88% to 96% [24,25]. US fusion with CT or MRI, can be used for percutaneous biopsy of lesions with poor sonographic conspicuity, with a 96% technical success rate [25]. Lesions that are isointense on CT can also present a challenge for CT-guided biopsy; however, use of anatomic landmarks or IV contrast can achieve accuracy of 96% to 98% [26]. Image-guided biopsies carry a risk of postbiopsy bleeding, which may be as high as 9% to 12%, particularly with hypervascular lesions [27,28]. In addition, a very small risk of needle-track seeding exists. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m red blood cell (RBC) scan in this clinical scenario.

Liver Lesion Initial Characterization. In some cases, MRI without IV contrast may be appropriate, particularly if the initial US has a high index of suspicion for the diagnosis of a cyst. Image-Guided Biopsy Liver An indeterminate liver lesion detected on US is often further evaluated with a diagnostic CT or MRI prior to biopsy, in order to avoid biopsy of solid benign liver lesions such as hemangiomas or areas of FNH [4]. Percutaneous image-guided biopsy may be necessary to establish the diagnosis, particularly when the imaging features on a CT or MRI examination indicate possibility of malignancy. In some liver lesions, such as lymphoma, histopathologic analysis is the only technique that can make a definitive diagnosis [20]. Various techniques exist for guidance of the biopsy, and US and CT are the most commonly utilized modalities for biopsy guidance. When a biopsy is performed to diagnose or rule out malignancy in indeterminate lesions, the overall technical success rate under grayscale US guidance is 74%, which can be increased to 100% under CEUS guidance [21,22]. The percentage of tumor cells in the biopsy sample is greater with a higher number of collected biopsy samples [23]. Furthermore, for lesions not seen on grayscale US, the success rate for CEUS-guided biopsy can be as high as 88% to 96% [24,25]. US fusion with CT or MRI, can be used for percutaneous biopsy of lesions with poor sonographic conspicuity, with a 96% technical success rate [25]. Lesions that are isointense on CT can also present a challenge for CT-guided biopsy; however, use of anatomic landmarks or IV contrast can achieve accuracy of 96% to 98% [26]. Image-guided biopsies carry a risk of postbiopsy bleeding, which may be as high as 9% to 12%, particularly with hypervascular lesions [27,28]. In addition, a very small risk of needle-track seeding exists. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m red blood cell (RBC) scan in this clinical scenario.

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acrac_69472_6

Liver Lesion Initial Characterization

Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen with Contrast For patients with a lesion on grayscale US, addition of CEUS reduces the number of indeterminate diagnoses from 57% to 6%, and the sensitivity and specificity improve from 49% and 25% at baseline US to 93% and 75% with CEUS, respectively [29]. Furthermore, CEUS can reach a specific diagnosis in 77% to 93% and distinguish benign versus malignant lesions in 89% to 97% of indeterminate liver lesions discovered on grayscale US [9,30-32]. Of the complex cystic lesions found on grayscale US, CEUS correctly categorizes 95% of the malignant cases [33]. CEUS is comparable to CT for establishing a diagnosis for lesions detected on grayscale US, with sensitivity of 94% to 96%, specificity of 75% to 83%, PPV of 92%, NPV of 88%, and accuracy of 88% to 90% [13,14,29]. CEUS can definitively characterize an additional 41% of hemangiomas that are deemed indeterminate on a grayscale US [34]. For specific diagnoses, CEUS correctly characterizes 89% of areas of focal fat, 80% to 90% of hemangiomas, 87% of complex cysts, 78% of hepatic adenomas, 84% to 94% of FNHs, 86% of abscesses, and 60% of hematomas [14,30,35]. Typical pattern of enhancement on CEUS (eg, centripetal fill in during the arterial phase, hyper- enhanced lesion during venous and late phases) has 88% to 90% sensitivity, 99% specificity, 94% to 95% PPV, 97% to 98% NPV, and 97% accuracy for the diagnosis of hemangiomas [18,36]. In noncirrhotic patients, the hypoechoic pattern in portal and sinusoidal phase (rapid wash-out) or the markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late wash-out) showed a sensitivity, specificity, and accuracy of 97%, 100% and 98%, respectively, for the diagnosis of malignancy [37].

Liver Lesion Initial Characterization. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen with Contrast For patients with a lesion on grayscale US, addition of CEUS reduces the number of indeterminate diagnoses from 57% to 6%, and the sensitivity and specificity improve from 49% and 25% at baseline US to 93% and 75% with CEUS, respectively [29]. Furthermore, CEUS can reach a specific diagnosis in 77% to 93% and distinguish benign versus malignant lesions in 89% to 97% of indeterminate liver lesions discovered on grayscale US [9,30-32]. Of the complex cystic lesions found on grayscale US, CEUS correctly categorizes 95% of the malignant cases [33]. CEUS is comparable to CT for establishing a diagnosis for lesions detected on grayscale US, with sensitivity of 94% to 96%, specificity of 75% to 83%, PPV of 92%, NPV of 88%, and accuracy of 88% to 90% [13,14,29]. CEUS can definitively characterize an additional 41% of hemangiomas that are deemed indeterminate on a grayscale US [34]. For specific diagnoses, CEUS correctly characterizes 89% of areas of focal fat, 80% to 90% of hemangiomas, 87% of complex cysts, 78% of hepatic adenomas, 84% to 94% of FNHs, 86% of abscesses, and 60% of hematomas [14,30,35]. Typical pattern of enhancement on CEUS (eg, centripetal fill in during the arterial phase, hyper- enhanced lesion during venous and late phases) has 88% to 90% sensitivity, 99% specificity, 94% to 95% PPV, 97% to 98% NPV, and 97% accuracy for the diagnosis of hemangiomas [18,36]. In noncirrhotic patients, the hypoechoic pattern in portal and sinusoidal phase (rapid wash-out) or the markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late wash-out) showed a sensitivity, specificity, and accuracy of 97%, 100% and 98%, respectively, for the diagnosis of malignancy [37].

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acrac_69472_7

Liver Lesion Initial Characterization

Liver Lesion-Initial Characterization Variant 2: Indeterminate, greater than 1 cm liver lesion on initial imaging with CT (noncontrast or single- phase) or noncontrast MRI. Normal liver. No suspicion or evidence of extrahepatic malignancy or underlying liver disease. CT Abdomen Contrast-enhanced CT correctly differentiates between malignant and benign lesions in 74% to 95% of lesions [9,10]. For patients with incidental liver lesions, multiphase contrast-enhanced CT has 91% to 95% accuracy for diagnosis of hemangioma, 85% to 93% accuracy for the diagnosis of FNH, and 96% to 99% accuracy for diagnosis of HCC [10,12]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT in this clinical scenario. DOTATATE PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of Ga-68-DOTATATE PET/CT in this clinical scenario. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen There is no relevant literature to support the use of In-111 somatostatin receptor scan with SPECT or SPECT/CT in this clinical scenario. Image-Guided Biopsy Liver Percutaneous image-guided biopsy may be necessary to establish the diagnosis, particularly when the imaging features on a CT or MRI examination indicate possibility of malignancy. In some liver lesions, such as lymphoma, histopathologic analysis is the only technique that can make a definitive diagnosis [20]. Various techniques exist for guidance of the biopsy, and US and CT are the most commonly utilized modalities for biopsy guidance. When a biopsy is performed to diagnose or rule out malignancy in indeterminate lesions, the overall technical success rate under grayscale US guidance is 74%, which can be increased to 100% under CEUS guidance [21,22].

Liver Lesion Initial Characterization. Liver Lesion-Initial Characterization Variant 2: Indeterminate, greater than 1 cm liver lesion on initial imaging with CT (noncontrast or single- phase) or noncontrast MRI. Normal liver. No suspicion or evidence of extrahepatic malignancy or underlying liver disease. CT Abdomen Contrast-enhanced CT correctly differentiates between malignant and benign lesions in 74% to 95% of lesions [9,10]. For patients with incidental liver lesions, multiphase contrast-enhanced CT has 91% to 95% accuracy for diagnosis of hemangioma, 85% to 93% accuracy for the diagnosis of FNH, and 96% to 99% accuracy for diagnosis of HCC [10,12]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT in this clinical scenario. DOTATATE PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of Ga-68-DOTATATE PET/CT in this clinical scenario. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen There is no relevant literature to support the use of In-111 somatostatin receptor scan with SPECT or SPECT/CT in this clinical scenario. Image-Guided Biopsy Liver Percutaneous image-guided biopsy may be necessary to establish the diagnosis, particularly when the imaging features on a CT or MRI examination indicate possibility of malignancy. In some liver lesions, such as lymphoma, histopathologic analysis is the only technique that can make a definitive diagnosis [20]. Various techniques exist for guidance of the biopsy, and US and CT are the most commonly utilized modalities for biopsy guidance. When a biopsy is performed to diagnose or rule out malignancy in indeterminate lesions, the overall technical success rate under grayscale US guidance is 74%, which can be increased to 100% under CEUS guidance [21,22].

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acrac_69472_8

Liver Lesion Initial Characterization

The percentage of tumor cells in the biopsy sample is greater with a higher number of collected biopsy samples [23]. Furthermore, for lesions not seen on grayscale US, the success rate for CEUS-guided biopsy can be as high as 88% to 96% [24,25]. US fusion with CT or MRI, can be used for percutaneous biopsy of lesions with poor sonographic conspicuity, with a 96% technical success rate [25]. Lesions that are isointense on CT can also present a challenge for CT-guided biopsy; however, use of anatomic landmarks or IV contrast can achieve accuracy of 96% to 98% [26]. Image-guided biopsies carry a risk of postbiopsy bleeding, which may be as high as 9% to 12%, particularly with hypervascular lesions [27,28]. In addition, a very small risk of needle-track seeding exists. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen Diagnostic accuracy of grayscale US is 41% to 68% for specific diagnosis and 86% for differentiation between malignant and benign lesions [9,29]. US can be helpful in some cases due to its ability to characterize a lesion as a Liver Lesion-Initial Characterization cyst. Doppler evaluation of flow is an integral part of the clinical grayscale US examination. However, none of the reviewed studies specifically compared performance of US examinations with and without the addition of Doppler. US Abdomen with Contrast In a small retrospective study of solid indeterminate lesions detected on contrast-enhanced CT in patients without parenchymal liver disease, addition of CEUS improves diagnostic accuracy from 43% to 49% to 89% to 92% [39]. CEUS is able to provide correct diagnosis in 89% of cases and can distinguish between benign and malignant lesions in 97% of cases [9].

Liver Lesion Initial Characterization. The percentage of tumor cells in the biopsy sample is greater with a higher number of collected biopsy samples [23]. Furthermore, for lesions not seen on grayscale US, the success rate for CEUS-guided biopsy can be as high as 88% to 96% [24,25]. US fusion with CT or MRI, can be used for percutaneous biopsy of lesions with poor sonographic conspicuity, with a 96% technical success rate [25]. Lesions that are isointense on CT can also present a challenge for CT-guided biopsy; however, use of anatomic landmarks or IV contrast can achieve accuracy of 96% to 98% [26]. Image-guided biopsies carry a risk of postbiopsy bleeding, which may be as high as 9% to 12%, particularly with hypervascular lesions [27,28]. In addition, a very small risk of needle-track seeding exists. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen Diagnostic accuracy of grayscale US is 41% to 68% for specific diagnosis and 86% for differentiation between malignant and benign lesions [9,29]. US can be helpful in some cases due to its ability to characterize a lesion as a Liver Lesion-Initial Characterization cyst. Doppler evaluation of flow is an integral part of the clinical grayscale US examination. However, none of the reviewed studies specifically compared performance of US examinations with and without the addition of Doppler. US Abdomen with Contrast In a small retrospective study of solid indeterminate lesions detected on contrast-enhanced CT in patients without parenchymal liver disease, addition of CEUS improves diagnostic accuracy from 43% to 49% to 89% to 92% [39]. CEUS is able to provide correct diagnosis in 89% of cases and can distinguish between benign and malignant lesions in 97% of cases [9].

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acrac_69472_9

Liver Lesion Initial Characterization

In noncirrhotic patients, the hypoechoic pattern in portal and sinusoidal phase (rapid wash-out) or the markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late wash-out) showed a sensitivity, specificity, and accuracy of 97%, 100%, and 98%, respectively, for the diagnosis of malignancy [37]. Variant 3: Indeterminate, greater than 1 cm liver lesion on initial imaging with US. Known history of an extrahepatic malignancy. CT Abdomen In patients with a history of primary malignancy, contrast-enhanced CT can differentiate between metastases and benign lesions with 74% accuracy [40]. Specifically, in patients with a history of colon cancer, lesion characterization on contrast-enhanced CT is correct in 77% of cases [41]. When metastases are suspected based on US, the sensitivity and specificity of contrast-enhanced CT for detection of metastases are 88% and 17%, respectively [42]. In patients with hypervascular liver metastases, addition of noncontrast CT can improve the confidence level for lesion characterization by 4% to 15%; however, it does not change the diagnostic accuracy [43]. The addition of noncontrast CT can increase sensitivity for breast cancer metastases by 5% to 23% but does not improve sensitivity for melanoma metastases [44]. Sensitivity of noncontrast CT alone is 61% to 100% for breast cancer metastases, 62% to 100% for melanoma metastases, and 17% to 88% for NET metastases [44]. In comparison, contrast- enhanced CT has sensitivity of 77% to 95% for breast cancer metastases, 86% to 100% for melanoma metastases, and 44% to 77% for NET metastases [44,45]. FDG-PET/CT Skull Base to Mid-Thigh In patients with a history of primary malignancy, FDG-PET/CT can differentiate between malignant and benign lesions with an accuracy of 75% [40].

Liver Lesion Initial Characterization. In noncirrhotic patients, the hypoechoic pattern in portal and sinusoidal phase (rapid wash-out) or the markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late wash-out) showed a sensitivity, specificity, and accuracy of 97%, 100%, and 98%, respectively, for the diagnosis of malignancy [37]. Variant 3: Indeterminate, greater than 1 cm liver lesion on initial imaging with US. Known history of an extrahepatic malignancy. CT Abdomen In patients with a history of primary malignancy, contrast-enhanced CT can differentiate between metastases and benign lesions with 74% accuracy [40]. Specifically, in patients with a history of colon cancer, lesion characterization on contrast-enhanced CT is correct in 77% of cases [41]. When metastases are suspected based on US, the sensitivity and specificity of contrast-enhanced CT for detection of metastases are 88% and 17%, respectively [42]. In patients with hypervascular liver metastases, addition of noncontrast CT can improve the confidence level for lesion characterization by 4% to 15%; however, it does not change the diagnostic accuracy [43]. The addition of noncontrast CT can increase sensitivity for breast cancer metastases by 5% to 23% but does not improve sensitivity for melanoma metastases [44]. Sensitivity of noncontrast CT alone is 61% to 100% for breast cancer metastases, 62% to 100% for melanoma metastases, and 17% to 88% for NET metastases [44]. In comparison, contrast- enhanced CT has sensitivity of 77% to 95% for breast cancer metastases, 86% to 100% for melanoma metastases, and 44% to 77% for NET metastases [44,45]. FDG-PET/CT Skull Base to Mid-Thigh In patients with a history of primary malignancy, FDG-PET/CT can differentiate between malignant and benign lesions with an accuracy of 75% [40].

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acrac_69472_10

Liver Lesion Initial Characterization

When metastases are suspected based on US, the sensitivity and specificity of PET/CT in the detection of hepatic metastases is 97% and 75%, respectively, which is higher, compared with contrast-enhanced CT alone with sensitivity and specificity of 88% and 17%, respectively [42]. DOTATATE PET/CT Skull Base to Mid-Thigh In patients with primary NET, Ga-68-DOTATATE PET/CT demonstrates sensitivity of 80% to 100% and of specificity 82% to 100% [8]. Specifically, Ga-68-DOTATATE PET/CT is more sensitive than FDG-PET/CT, with sensitivities of 72% to 100% versus 54% to 78%, respectively [8]. Ga-68-DOTATATE PET/CT is not used in assessment metastases from primary cancers other than NET. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen Sensitivity of In-111 somatostatin receptor scan with SPECT or SPECT/CT varies depending on the specific histologic type of the primary NET. For example, detection rates are >75% in small-cell-lung cancer and carcinoid metastases and 40% to 75% in insulinoma and medullary thyroid cancers [46]. Image-Guided Biopsy Liver Percutaneous image-guided biopsy may be necessary to establish the diagnosis, particularly when the imaging features on a CT or MRI examination indicate a possibility of malignancy. In some liver lesions, such as lymphoma, histopathologic analysis is the only technique that can make a definitive diagnosis [20]. Various techniques exist Liver Lesion-Initial Characterization for guidance of the biopsy, where US and CT are the most commonly utilized modalities for biopsy guidance. When a biopsy is performed to diagnose or rule out malignancy in indeterminate lesions, the overall technical success rate under grayscale US guidance is 74%, which can be increased to 100% under CEUS guidance [21,22]. The percentage of tumor cells in the biopsy sample is greater with a higher number of collected biopsy samples [23].

Liver Lesion Initial Characterization. When metastases are suspected based on US, the sensitivity and specificity of PET/CT in the detection of hepatic metastases is 97% and 75%, respectively, which is higher, compared with contrast-enhanced CT alone with sensitivity and specificity of 88% and 17%, respectively [42]. DOTATATE PET/CT Skull Base to Mid-Thigh In patients with primary NET, Ga-68-DOTATATE PET/CT demonstrates sensitivity of 80% to 100% and of specificity 82% to 100% [8]. Specifically, Ga-68-DOTATATE PET/CT is more sensitive than FDG-PET/CT, with sensitivities of 72% to 100% versus 54% to 78%, respectively [8]. Ga-68-DOTATATE PET/CT is not used in assessment metastases from primary cancers other than NET. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen Sensitivity of In-111 somatostatin receptor scan with SPECT or SPECT/CT varies depending on the specific histologic type of the primary NET. For example, detection rates are >75% in small-cell-lung cancer and carcinoid metastases and 40% to 75% in insulinoma and medullary thyroid cancers [46]. Image-Guided Biopsy Liver Percutaneous image-guided biopsy may be necessary to establish the diagnosis, particularly when the imaging features on a CT or MRI examination indicate a possibility of malignancy. In some liver lesions, such as lymphoma, histopathologic analysis is the only technique that can make a definitive diagnosis [20]. Various techniques exist Liver Lesion-Initial Characterization for guidance of the biopsy, where US and CT are the most commonly utilized modalities for biopsy guidance. When a biopsy is performed to diagnose or rule out malignancy in indeterminate lesions, the overall technical success rate under grayscale US guidance is 74%, which can be increased to 100% under CEUS guidance [21,22]. The percentage of tumor cells in the biopsy sample is greater with a higher number of collected biopsy samples [23].

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acrac_69472_11

Liver Lesion Initial Characterization

Furthermore, for lesions not seen on grayscale US, the success rate for CEUS-guided biopsy can be as high as 88% to 96% [24,25]. US fusion with CT or MRI can be used for percutaneous biopsy of lesions with poor sonographic conspicuity with a 96% technical success rate [25]. Lesions which are isointense on CT can also present a challenge for CT-guided biopsy; however, use of anatomic landmarks or IV contrast can achieve accuracy of 96% to 98% [26]. Image-guided biopsies carry a risk of postbiopsy bleeding, which may be as high as 9% to 12%, particularly with hypervascular lesions [27,28]. In addition, a very small risk of needle-track seeding exists. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen with Contrast Depending on the appearance of the lesion on the initial US, CEUS may be performed for lesion characterization. CEUS can differentiate between malignant and benign lesions in 90% of lesions [48]. Diagnostic accuracy of CEUS for metastases is 83% compared with 76% for MRI with extracellular contrast agent [35]. In noncirrhotic patients, the hypoechoic pattern in portal and sinusoidal phase (rapid wash-out) or the markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late wash-out) showed a sensitivity, specificity, and accuracy of 97%, 100%, and 98%, respectively, for the diagnosis of malignancy [37]. Variant 4: Indeterminate, greater than 1 cm liver lesion on initial imaging with CT (noncontrast or single- phase) or noncontrast MRI. Known history of an extrahepatic malignancy. CT Abdomen In patients with a history of primary malignancy, contrast-enhanced CT can differentiate between metastases and benign lesions with 74% accuracy [40].

Liver Lesion Initial Characterization. Furthermore, for lesions not seen on grayscale US, the success rate for CEUS-guided biopsy can be as high as 88% to 96% [24,25]. US fusion with CT or MRI can be used for percutaneous biopsy of lesions with poor sonographic conspicuity with a 96% technical success rate [25]. Lesions which are isointense on CT can also present a challenge for CT-guided biopsy; however, use of anatomic landmarks or IV contrast can achieve accuracy of 96% to 98% [26]. Image-guided biopsies carry a risk of postbiopsy bleeding, which may be as high as 9% to 12%, particularly with hypervascular lesions [27,28]. In addition, a very small risk of needle-track seeding exists. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen with Contrast Depending on the appearance of the lesion on the initial US, CEUS may be performed for lesion characterization. CEUS can differentiate between malignant and benign lesions in 90% of lesions [48]. Diagnostic accuracy of CEUS for metastases is 83% compared with 76% for MRI with extracellular contrast agent [35]. In noncirrhotic patients, the hypoechoic pattern in portal and sinusoidal phase (rapid wash-out) or the markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late wash-out) showed a sensitivity, specificity, and accuracy of 97%, 100%, and 98%, respectively, for the diagnosis of malignancy [37]. Variant 4: Indeterminate, greater than 1 cm liver lesion on initial imaging with CT (noncontrast or single- phase) or noncontrast MRI. Known history of an extrahepatic malignancy. CT Abdomen In patients with a history of primary malignancy, contrast-enhanced CT can differentiate between metastases and benign lesions with 74% accuracy [40].

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Liver Lesion Initial Characterization

Specifically, in patients with a history of colon cancer, lesion characterization on contrast-enhanced CT is correct in 77% of cases [41]. In patients with hypervascular liver metastases, adding a noncontrast CT phase to a contrast-enhanced CT examination can improve the confidence level for lesion characterization by 4% to 15%; however, it does not change the diagnostic accuracy [43]. The addition of noncontrast CT can increase sensitivity for breast cancer metastases by 5% to 23% but does not improve sensitivity for melanoma metastases [44]. Sensitivity of noncontrast CT alone is 61% to 100% for breast cancer metastases, 62% to 100% for melanoma metastases, and 17% to 88% for NET metastases [44]. In comparison, contrast-enhanced CT has a sensitivity of 77% to 95% for breast cancer metastases, 86% to 100% for melanoma metastases, and 44% to 82% for NET metastases [44,45]. FDG-PET/CT Skull Base to Mid-Thigh In patients with a history of primary malignancy, FDG-PET/CT can differentiate between malignant and benign lesions with an accuracy of 75% [40]. In patients with a history of primary cancer and indeterminate lesions found by either CT or MRI, FDG-PET/CT has an accuracy of 75% with a high sensitivity of 96% and a limited specificity of 33% [40]. The sensitivity and specificity of FDG-PET/CT in the detection of hepatic metastases is 97% and 75%, respectively, which is higher compared with contrast-enhanced CT alone (which as a sensitivity and specificity of 88% and 17%, respectively) [42]. DOTATATE PET/CT Skull Base to Mid-Thigh In patients with primary NET, Ga-68-DOTATATE PET/CT demonstrates sensitivity of 80% to 100% and specificity of 82% to 100% [8]. Specifically, Ga-68-DOTATATE PET/CT is more sensitive than FDG-PET/CT, with sensitivities of 72% to 100% versus 54% to 78%, respectively [8]. Liver Lesion-Initial Characterization

Liver Lesion Initial Characterization. Specifically, in patients with a history of colon cancer, lesion characterization on contrast-enhanced CT is correct in 77% of cases [41]. In patients with hypervascular liver metastases, adding a noncontrast CT phase to a contrast-enhanced CT examination can improve the confidence level for lesion characterization by 4% to 15%; however, it does not change the diagnostic accuracy [43]. The addition of noncontrast CT can increase sensitivity for breast cancer metastases by 5% to 23% but does not improve sensitivity for melanoma metastases [44]. Sensitivity of noncontrast CT alone is 61% to 100% for breast cancer metastases, 62% to 100% for melanoma metastases, and 17% to 88% for NET metastases [44]. In comparison, contrast-enhanced CT has a sensitivity of 77% to 95% for breast cancer metastases, 86% to 100% for melanoma metastases, and 44% to 82% for NET metastases [44,45]. FDG-PET/CT Skull Base to Mid-Thigh In patients with a history of primary malignancy, FDG-PET/CT can differentiate between malignant and benign lesions with an accuracy of 75% [40]. In patients with a history of primary cancer and indeterminate lesions found by either CT or MRI, FDG-PET/CT has an accuracy of 75% with a high sensitivity of 96% and a limited specificity of 33% [40]. The sensitivity and specificity of FDG-PET/CT in the detection of hepatic metastases is 97% and 75%, respectively, which is higher compared with contrast-enhanced CT alone (which as a sensitivity and specificity of 88% and 17%, respectively) [42]. DOTATATE PET/CT Skull Base to Mid-Thigh In patients with primary NET, Ga-68-DOTATATE PET/CT demonstrates sensitivity of 80% to 100% and specificity of 82% to 100% [8]. Specifically, Ga-68-DOTATATE PET/CT is more sensitive than FDG-PET/CT, with sensitivities of 72% to 100% versus 54% to 78%, respectively [8]. Liver Lesion-Initial Characterization

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Liver Lesion Initial Characterization

Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen Sensitivity of a In-111 somatostatin receptor scan with SPECT or SPECT/CT varies depending on the specific histologic type of the primary NET. For example, detection rates are >75% in small-cell-lung cancer and carcinoid metastases and 40% to 75% in insulinoma and medullary thyroid cancers [46]. MRI Abdomen In patients with a history of primary malignancy, noncontrast MRI can differentiate between malignant and benign lesions with accuracy of 71% [47]. The accuracy increases by between 83% and 91% with the addition of dynamic postcontrast sequences and further increases to 94% with addition of HBP [47,48]. In patients with a history of colon cancer, the lesion characterization on contrast-enhanced MRI is correct in 89% of cases [41]. In patients with suspected colorectal liver metastases, the combination of gadoxetate-enhanced MRI and DWI shows significantly higher accuracy (90% to 93%) for the preoperative detection of small colorectal liver metastases than DWI alone [49]. In patients with known primary cancer, ADC values can help to distinguish between metastasis and benign solid hepatic lesions [50]. Image-Guided Biopsy Liver Percutaneous image-guided biopsy may be necessary to establish the diagnosis, particularly when the imaging features on a CT or MRI examination indicate possibility of malignancy. In patients with a history of primary malignancy, 91% of biopsies are positive for malignancy, 5% of which can be different from the primary cancer [51]. Up to 6% of biopsies in patients with primary malignancy are nondiagnostic [51]. In some liver lesions, such as lymphoma, histopathologic analysis is the only technique that can make a definitive diagnosis [20]. Various techniques exist for guidance of the biopsy, and US and CT are the most commonly utilized modalities for biopsy guidance.

Liver Lesion Initial Characterization. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen Sensitivity of a In-111 somatostatin receptor scan with SPECT or SPECT/CT varies depending on the specific histologic type of the primary NET. For example, detection rates are >75% in small-cell-lung cancer and carcinoid metastases and 40% to 75% in insulinoma and medullary thyroid cancers [46]. MRI Abdomen In patients with a history of primary malignancy, noncontrast MRI can differentiate between malignant and benign lesions with accuracy of 71% [47]. The accuracy increases by between 83% and 91% with the addition of dynamic postcontrast sequences and further increases to 94% with addition of HBP [47,48]. In patients with a history of colon cancer, the lesion characterization on contrast-enhanced MRI is correct in 89% of cases [41]. In patients with suspected colorectal liver metastases, the combination of gadoxetate-enhanced MRI and DWI shows significantly higher accuracy (90% to 93%) for the preoperative detection of small colorectal liver metastases than DWI alone [49]. In patients with known primary cancer, ADC values can help to distinguish between metastasis and benign solid hepatic lesions [50]. Image-Guided Biopsy Liver Percutaneous image-guided biopsy may be necessary to establish the diagnosis, particularly when the imaging features on a CT or MRI examination indicate possibility of malignancy. In patients with a history of primary malignancy, 91% of biopsies are positive for malignancy, 5% of which can be different from the primary cancer [51]. Up to 6% of biopsies in patients with primary malignancy are nondiagnostic [51]. In some liver lesions, such as lymphoma, histopathologic analysis is the only technique that can make a definitive diagnosis [20]. Various techniques exist for guidance of the biopsy, and US and CT are the most commonly utilized modalities for biopsy guidance.

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Liver Lesion Initial Characterization

When a biopsy is performed to diagnose or rule out malignancy in indeterminate lesions, the overall technical success rate under grayscale US guidance is 74%, which can be increased to 100% under CEUS guidance [21,22]. The percentage of tumor cells in the biopsy sample is greater with a higher number of collected biopsy samples [23]. Furthermore, for lesions not seen on grayscale US, the success rate for CEUS-guided biopsy can be as high as 88% to 96% [24,25]. US fusion with CT or MRI, can be used for percutaneous biopsy of lesions with poor sonographic conspicuity, with a 96% technical success rate [25]. Lesions that are isointense on CT can also present a challenge for CT-guided biopsy; however, use of anatomic landmarks or IV contrast can achieve an accuracy of 96% to 98% [26]. The image-guided biopsies carry a risk of postbiopsy bleeding that may be as high as 9% to 12%, particularly with hypervascular lesions [27,28]. In addition, a small risk of needle-track seeding exists. In patients with HCC, the rate of seeding is 0.1% to 0.7% [52-54]. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen Grayscale US is able to provide correct diagnosis in 68% of liver lesions [9]. For differentiation between malignant and benign lesions, US is correct in 86% of cases [9]. US Abdomen with Contrast In noncirrhotic patients, the hypoechoic pattern in portal and sinusoidal phase (rapid wash-out) or the markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late wash-out) showed a sensitivity, specificity, and accuracy of 97%, 100%, and 98%, respectively, for the diagnosis of malignancy [37].

Liver Lesion Initial Characterization. When a biopsy is performed to diagnose or rule out malignancy in indeterminate lesions, the overall technical success rate under grayscale US guidance is 74%, which can be increased to 100% under CEUS guidance [21,22]. The percentage of tumor cells in the biopsy sample is greater with a higher number of collected biopsy samples [23]. Furthermore, for lesions not seen on grayscale US, the success rate for CEUS-guided biopsy can be as high as 88% to 96% [24,25]. US fusion with CT or MRI, can be used for percutaneous biopsy of lesions with poor sonographic conspicuity, with a 96% technical success rate [25]. Lesions that are isointense on CT can also present a challenge for CT-guided biopsy; however, use of anatomic landmarks or IV contrast can achieve an accuracy of 96% to 98% [26]. The image-guided biopsies carry a risk of postbiopsy bleeding that may be as high as 9% to 12%, particularly with hypervascular lesions [27,28]. In addition, a small risk of needle-track seeding exists. In patients with HCC, the rate of seeding is 0.1% to 0.7% [52-54]. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen Grayscale US is able to provide correct diagnosis in 68% of liver lesions [9]. For differentiation between malignant and benign lesions, US is correct in 86% of cases [9]. US Abdomen with Contrast In noncirrhotic patients, the hypoechoic pattern in portal and sinusoidal phase (rapid wash-out) or the markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late wash-out) showed a sensitivity, specificity, and accuracy of 97%, 100%, and 98%, respectively, for the diagnosis of malignancy [37].

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acrac_69472_15

Liver Lesion Initial Characterization

In a small retrospective study of patients with primary pancreatic adenocarcinoma, CT and CEUS have similar sensitivities for detection of metastases (73% versus 80%, respectively) [2]. However, CEUS is able to more accurately differentiate between an incidental benign lesion (eg, cysts, vascular shunts) from metastases, resulting in fewer false-positive diagnoses and therefore higher PPV (60% versus 92%) [2]. The accuracy of CEUS for diagnosis of metastases is 76% [35]. Liver Lesion-Initial Characterization Variant 5: Incidental liver lesion, greater than 1 cm on US, noncontrast or single-phase CT, or noncontrast MRI. Known chronic liver disease. Evaluation of liver lesions detected in a patient with chronic liver disease should be performed based on the algorithm set forth by the most recent version of LI-RADS [6,55]. CT Abdomen The sensitivity of a dual-phase contrast-enhanced CT for diagnosing a small HCC (<2 cm) is 53% [56]. In patients with chronic liver disease, triple-phase contrast-enhanced CT correctly characterizes lesions in 49% to 68% of cases and has a sensitivity of 61% to 73% for lesion detection [57]. Delayed phase wash-out on CT is important in HCC diagnosis [58]. For 1- to 2-cm lesions in patients with cirrhosis detected on screening US, the addition of noncontrast CT to dynamic postcontrast phases (CT without and with IV contrast) does not increase sensitivity or accuracy for HCC [59]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT has a limited role in characterization of liver lesions in patients with parenchymal liver disease [6]. Once the diagnosis of HCC is established, tumor FDG activity may predict microvascular invasion [60]. DOTATATE PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of Ga-68-DOTATATE PET/CT in this clinical scenario.

Liver Lesion Initial Characterization. In a small retrospective study of patients with primary pancreatic adenocarcinoma, CT and CEUS have similar sensitivities for detection of metastases (73% versus 80%, respectively) [2]. However, CEUS is able to more accurately differentiate between an incidental benign lesion (eg, cysts, vascular shunts) from metastases, resulting in fewer false-positive diagnoses and therefore higher PPV (60% versus 92%) [2]. The accuracy of CEUS for diagnosis of metastases is 76% [35]. Liver Lesion-Initial Characterization Variant 5: Incidental liver lesion, greater than 1 cm on US, noncontrast or single-phase CT, or noncontrast MRI. Known chronic liver disease. Evaluation of liver lesions detected in a patient with chronic liver disease should be performed based on the algorithm set forth by the most recent version of LI-RADS [6,55]. CT Abdomen The sensitivity of a dual-phase contrast-enhanced CT for diagnosing a small HCC (<2 cm) is 53% [56]. In patients with chronic liver disease, triple-phase contrast-enhanced CT correctly characterizes lesions in 49% to 68% of cases and has a sensitivity of 61% to 73% for lesion detection [57]. Delayed phase wash-out on CT is important in HCC diagnosis [58]. For 1- to 2-cm lesions in patients with cirrhosis detected on screening US, the addition of noncontrast CT to dynamic postcontrast phases (CT without and with IV contrast) does not increase sensitivity or accuracy for HCC [59]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT has a limited role in characterization of liver lesions in patients with parenchymal liver disease [6]. Once the diagnosis of HCC is established, tumor FDG activity may predict microvascular invasion [60]. DOTATATE PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of Ga-68-DOTATATE PET/CT in this clinical scenario.

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acrac_69472_16

Liver Lesion Initial Characterization

Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen There is no relevant literature to support the use of In-111 somatostatin receptor scan with SPECT or SPECT/CT in this clinical scenario. MRI with extracellular agents has a sensitivity of 78% to 83% and specificity of 100% [35,61]. Addition of HBP improves sensitivity and accuracy for nodules <2 cm [62]. The sensitivity of MRI with gadoxetate for diagnosing a small HCC (<2 cm) is 76% to 97% [56,63]. Addition of HBP improves detection of HCC and differentiation between HCC and dysplastic nodules [64,65]. Furthermore, addition of HBP improves sensitivity and accuracy for diagnosis of HCC, compared with the dynamic images alone [66,67]. Gadoxetate-enhanced MRI allows for correct characterization of liver lesions in 87% to 91% of cases [63]. However, the HBP on gadoxetate-enhanced MRI can be limited in the setting of poor liver function, and transient hepatic enhancement differences can cause artifacts in the HBP in cirrhotic patients [68,69]. In patients with chronic liver disease, the mean ADC values in benign solid lesions are higher than those in malignant lesions [70]. In small (<3 cm) lesions, presence of high signal intensity on both T2-weighted imaging and DWI helps differentiate atypical HCCs from dysplastic nodules, with the resultant sensitivity of 80%, specificity of 100%, PPV of 100%, and NPV of 78.3% [71]. For lesions <3 cm in patients with cirrhosis, the sensitivity and accuracy to differentiate the dysplastic nodule from HCC are 46% to 82% and 57% to 75%, respectively [72,73]. The addition of DWI to dynamic sequences improved its ability to distinguish between HCC and dysplastic nodules compared with dynamic sequences alone, with a resultant accuracy of 93% and sensitivity of 97% [73].

Liver Lesion Initial Characterization. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen There is no relevant literature to support the use of In-111 somatostatin receptor scan with SPECT or SPECT/CT in this clinical scenario. MRI with extracellular agents has a sensitivity of 78% to 83% and specificity of 100% [35,61]. Addition of HBP improves sensitivity and accuracy for nodules <2 cm [62]. The sensitivity of MRI with gadoxetate for diagnosing a small HCC (<2 cm) is 76% to 97% [56,63]. Addition of HBP improves detection of HCC and differentiation between HCC and dysplastic nodules [64,65]. Furthermore, addition of HBP improves sensitivity and accuracy for diagnosis of HCC, compared with the dynamic images alone [66,67]. Gadoxetate-enhanced MRI allows for correct characterization of liver lesions in 87% to 91% of cases [63]. However, the HBP on gadoxetate-enhanced MRI can be limited in the setting of poor liver function, and transient hepatic enhancement differences can cause artifacts in the HBP in cirrhotic patients [68,69]. In patients with chronic liver disease, the mean ADC values in benign solid lesions are higher than those in malignant lesions [70]. In small (<3 cm) lesions, presence of high signal intensity on both T2-weighted imaging and DWI helps differentiate atypical HCCs from dysplastic nodules, with the resultant sensitivity of 80%, specificity of 100%, PPV of 100%, and NPV of 78.3% [71]. For lesions <3 cm in patients with cirrhosis, the sensitivity and accuracy to differentiate the dysplastic nodule from HCC are 46% to 82% and 57% to 75%, respectively [72,73]. The addition of DWI to dynamic sequences improved its ability to distinguish between HCC and dysplastic nodules compared with dynamic sequences alone, with a resultant accuracy of 93% and sensitivity of 97% [73].

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acrac_69472_17

Liver Lesion Initial Characterization

Image-Guided Biopsy Liver Biopsy plays a minor role in establishing the diagnosis of HCC because the imaging criteria of LI-RADS category 5 (definite HCC) can establish such diagnosis with nearly 100% specificity and PPV [6,74]. Biopsy may be necessary if the imaging features of the lesion do not meet the criteria for LI-RADS 5 (definite HCC) category or for molecular analysis to determine clinical trial eligibility or to guide treatment [74]. Overall risk of bleeding for image-guided biopsy can be as high as 12% [27]. An additional risk in biopsy of HCC is a risk of needle-tract seeding, with track seeding incidence being 2.7% overall and 0.1% to 0.9% per year [52-54,75]. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. Liver Lesion-Initial Characterization US Abdomen with Contrast For indeterminate liver lesions detected on US, CEUS can provide definitive diagnosis in 77% to 93% of cases and can distinguish between benign and malignant lesions in 89% to 96% of cases [31,32]. The sensitivity of CEUS for diagnosing a small HCC (<2 cm) is 68% compared with 53% for contrast-enhanced CT and 77% for gadolinium- ethoxybenzyl-diethylenetriamine pentaacetic acid MRI in the same study [56]. Diagnostic accuracy of CEUS for HCC is 79% [35]. On CEUS, HCC typically shows a global arterial hyperenhancement and a delayed contrast wash-out, whereas intrahepatic cholangiocarcinoma shows an initial contrast enhancement primarily at the tumor periphery followed by an early portal-venous contrast wash-out in the tumor center [78]. CEUS can accurately differentiate between intrahepatic cholangiocarcinoma and HCC [79]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images.

Liver Lesion Initial Characterization. Image-Guided Biopsy Liver Biopsy plays a minor role in establishing the diagnosis of HCC because the imaging criteria of LI-RADS category 5 (definite HCC) can establish such diagnosis with nearly 100% specificity and PPV [6,74]. Biopsy may be necessary if the imaging features of the lesion do not meet the criteria for LI-RADS 5 (definite HCC) category or for molecular analysis to determine clinical trial eligibility or to guide treatment [74]. Overall risk of bleeding for image-guided biopsy can be as high as 12% [27]. An additional risk in biopsy of HCC is a risk of needle-tract seeding, with track seeding incidence being 2.7% overall and 0.1% to 0.9% per year [52-54,75]. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. Liver Lesion-Initial Characterization US Abdomen with Contrast For indeterminate liver lesions detected on US, CEUS can provide definitive diagnosis in 77% to 93% of cases and can distinguish between benign and malignant lesions in 89% to 96% of cases [31,32]. The sensitivity of CEUS for diagnosing a small HCC (<2 cm) is 68% compared with 53% for contrast-enhanced CT and 77% for gadolinium- ethoxybenzyl-diethylenetriamine pentaacetic acid MRI in the same study [56]. Diagnostic accuracy of CEUS for HCC is 79% [35]. On CEUS, HCC typically shows a global arterial hyperenhancement and a delayed contrast wash-out, whereas intrahepatic cholangiocarcinoma shows an initial contrast enhancement primarily at the tumor periphery followed by an early portal-venous contrast wash-out in the tumor center [78]. CEUS can accurately differentiate between intrahepatic cholangiocarcinoma and HCC [79]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images.

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Liver Lesion Initial Characterization

FDG-PET/CT Skull Base to Mid-Thigh In patients with a history of primary malignancy, FDG-PET/CT may be indicated to evaluate for presence of metastases beyond the liver. Current literature does not support the use of FGD-PET/CT specifically to characterize subcentimeter liver lesions due to its limited sensitivity for lesions <1 cm. DOTATATE PET/CT Skull Base to Mid-Thigh Ga-68-DOTATATE PET/CT is sensitive for detection of metastases in patients with primary NET; however, there is no relevant literature on assessment of subcentimeter liver lesions. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen In patients with a history of primary NET, In-111 somatostatin receptor scan with SPECT or SPECT/CT can detect liver metastases; however, there is no relevant literature to support the use of this procedure in characterization of subcentimeter liver lesions. MRI Abdomen On MRI with gadoxetate, the combination of HBP and DWI has the highest accuracy for detection of subcentimeter liver lesions [15]. ADC values can help differentiate benign versus malignant subcentimeter liver lesions with 92% to 93% accuracy [84]. There is no relevant literature that has assessed the performance of MRI without IV contrast specifically for this clinical scenario. Therefore, the committee recommendations on the use of MRI without IV contrast are based primarily on expert opinion. In some cases, MRI without IV contrast may be appropriate as it can differentiate between small cysts and solid lesions. Image-Guided Biopsy Liver Tissue sampling may be necessary to establish the definitive diagnosis in patients with a history of primary malignancy and indeterminate subcentimeter liver lesions. However, the role of percutaneous biopsy is limited in the evaluation of subcentimeter liver lesions because such lesions are typically difficult to target under image guidance. Furthermore, there is no relevant literature to assess performance of percutaneous biopsy techniques for subcentimeter liver lesions.

Liver Lesion Initial Characterization. FDG-PET/CT Skull Base to Mid-Thigh In patients with a history of primary malignancy, FDG-PET/CT may be indicated to evaluate for presence of metastases beyond the liver. Current literature does not support the use of FGD-PET/CT specifically to characterize subcentimeter liver lesions due to its limited sensitivity for lesions <1 cm. DOTATATE PET/CT Skull Base to Mid-Thigh Ga-68-DOTATATE PET/CT is sensitive for detection of metastases in patients with primary NET; however, there is no relevant literature on assessment of subcentimeter liver lesions. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen In patients with a history of primary NET, In-111 somatostatin receptor scan with SPECT or SPECT/CT can detect liver metastases; however, there is no relevant literature to support the use of this procedure in characterization of subcentimeter liver lesions. MRI Abdomen On MRI with gadoxetate, the combination of HBP and DWI has the highest accuracy for detection of subcentimeter liver lesions [15]. ADC values can help differentiate benign versus malignant subcentimeter liver lesions with 92% to 93% accuracy [84]. There is no relevant literature that has assessed the performance of MRI without IV contrast specifically for this clinical scenario. Therefore, the committee recommendations on the use of MRI without IV contrast are based primarily on expert opinion. In some cases, MRI without IV contrast may be appropriate as it can differentiate between small cysts and solid lesions. Image-Guided Biopsy Liver Tissue sampling may be necessary to establish the definitive diagnosis in patients with a history of primary malignancy and indeterminate subcentimeter liver lesions. However, the role of percutaneous biopsy is limited in the evaluation of subcentimeter liver lesions because such lesions are typically difficult to target under image guidance. Furthermore, there is no relevant literature to assess performance of percutaneous biopsy techniques for subcentimeter liver lesions.

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Liver Lesion Initial Characterization

Liver Lesion-Initial Characterization RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen with Contrast Compared with a baseline grayscale US, CEUS can detect 6.5 times more subcentimeter metastases [9]. For indeterminate liver lesions discovered on grayscale US, CEUS reached a specific diagnosis in 83% of cases and distinguished benign versus malignant in 90% of cases [30]. For the benign diagnoses, CEUS correctly characterized 89% of areas of focal fat, 90% of hemangiomas, 87% of complex cysts, 78% of hepatic adenomas, 90% of FNHs, 86% of abscesses, and 60% of hematomas [30]. CEUS correctly characterized 86% of metastases [30]. Variant 7: Indeterminate, less than 1 cm liver lesion on initial imaging with CT (noncontrast or single-phase) or noncontrast MRI. Known history of an extrahepatic malignancy. CT Abdomen Subcentimeter liver lesions in patients with primary malignancy are seen on contrast-enhanced CT in 13% of patients, and of these, 12% are metastases [82]. Among patients with a history of colorectal and breast cancers, small hepatic lesions were metastatic in 14% and 22% of cases, respectively [82]. Subcentimeter liver lesions in women with breast cancer can be found in 29%, and if no obvious liver metastases are present, 93% to 97% of these subcentimeter liver lesions are benign [85]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images. FDG-PET/CT Skull Base to Mid-Thigh In patients with a history of primary malignancy, FDG-PET/CT may be indicated to evaluate for the presence of metastases beyond the liver.

Liver Lesion Initial Characterization. Liver Lesion-Initial Characterization RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. US Abdomen with Contrast Compared with a baseline grayscale US, CEUS can detect 6.5 times more subcentimeter metastases [9]. For indeterminate liver lesions discovered on grayscale US, CEUS reached a specific diagnosis in 83% of cases and distinguished benign versus malignant in 90% of cases [30]. For the benign diagnoses, CEUS correctly characterized 89% of areas of focal fat, 90% of hemangiomas, 87% of complex cysts, 78% of hepatic adenomas, 90% of FNHs, 86% of abscesses, and 60% of hematomas [30]. CEUS correctly characterized 86% of metastases [30]. Variant 7: Indeterminate, less than 1 cm liver lesion on initial imaging with CT (noncontrast or single-phase) or noncontrast MRI. Known history of an extrahepatic malignancy. CT Abdomen Subcentimeter liver lesions in patients with primary malignancy are seen on contrast-enhanced CT in 13% of patients, and of these, 12% are metastases [82]. Among patients with a history of colorectal and breast cancers, small hepatic lesions were metastatic in 14% and 22% of cases, respectively [82]. Subcentimeter liver lesions in women with breast cancer can be found in 29%, and if no obvious liver metastases are present, 93% to 97% of these subcentimeter liver lesions are benign [85]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images. FDG-PET/CT Skull Base to Mid-Thigh In patients with a history of primary malignancy, FDG-PET/CT may be indicated to evaluate for the presence of metastases beyond the liver.

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acrac_69472_20

Liver Lesion Initial Characterization

There is no relevant literature to support the use of FDG-PET/CT specifically to characterize subcentimeter liver lesions due to its limited sensitivity for lesions <1 cm. DOTATATE PET/CT Skull Base to Mid-Thigh Ga-68-DOTATATE PET/CT is sensitive for detection of metastases in patients with primary NET; however, there is no relevant literature on assessment of subcentimeter liver lesions. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen In patients with a history of primary NET, In-111 somatostatin receptor scan with SPECT or SPECT/CT can detect liver metastases; however, there is no relevant literature on assessment of subcentimeter liver lesions. MRI Abdomen For subcentimeter liver lesions detected on CT, the sensitivity, specificity, PPV, and NPV for differentiation of benign from malignant lesions for contrast-enhanced MRI are 83%, 98%, 92%, and 94%, respectively [86]. In patients with a history of colon cancer, MRI has a sensitivity of 60% for detection of subcentimeter metastases [87]. There is no relevant literature that has assessed the performance of MRI without IV contrast specifically for this clinical scenario. Therefore, the committee recommendations on the use of MRI without IV contrast are based primarily on expert opinion. Image-Guided Biopsy Liver Tissue sampling may be necessary to establish the definitive diagnosis in patients with a history of primary malignancy and indeterminate subcentimeter liver lesions. However, the role of percutaneous biopsy is limited in the evaluation of subcentimeter liver lesions because such lesions are typically difficult to target under image guidance. Furthermore, published data are not available to assess performance of percutaneous biopsy techniques for subcentimeter liver lesions. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario.

Liver Lesion Initial Characterization. There is no relevant literature to support the use of FDG-PET/CT specifically to characterize subcentimeter liver lesions due to its limited sensitivity for lesions <1 cm. DOTATATE PET/CT Skull Base to Mid-Thigh Ga-68-DOTATATE PET/CT is sensitive for detection of metastases in patients with primary NET; however, there is no relevant literature on assessment of subcentimeter liver lesions. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen In patients with a history of primary NET, In-111 somatostatin receptor scan with SPECT or SPECT/CT can detect liver metastases; however, there is no relevant literature on assessment of subcentimeter liver lesions. MRI Abdomen For subcentimeter liver lesions detected on CT, the sensitivity, specificity, PPV, and NPV for differentiation of benign from malignant lesions for contrast-enhanced MRI are 83%, 98%, 92%, and 94%, respectively [86]. In patients with a history of colon cancer, MRI has a sensitivity of 60% for detection of subcentimeter metastases [87]. There is no relevant literature that has assessed the performance of MRI without IV contrast specifically for this clinical scenario. Therefore, the committee recommendations on the use of MRI without IV contrast are based primarily on expert opinion. Image-Guided Biopsy Liver Tissue sampling may be necessary to establish the definitive diagnosis in patients with a history of primary malignancy and indeterminate subcentimeter liver lesions. However, the role of percutaneous biopsy is limited in the evaluation of subcentimeter liver lesions because such lesions are typically difficult to target under image guidance. Furthermore, published data are not available to assess performance of percutaneous biopsy techniques for subcentimeter liver lesions. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario.

69472

acrac_69472_21

Liver Lesion Initial Characterization

Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. Liver Lesion-Initial Characterization US Abdomen In patients with a history of primary malignancy and indeterminate, subcentimeter focal liver lesions on CT, grayscale US is able to prove cystic nature of the lesion in 67% of cases [88]. US Abdomen with Contrast In patients with a history of primary malignancy and indeterminate, subcentimeter focal liver lesions on CT that were proven to be noncystic on grayscale US, CEUS correctly characterizes 95% of lesions overall, and 98% of metastases [88]. Compared with a baseline dual-phase contrast-enhanced CT, CEUS can detect 6.5 times more subcentimeter metastases [9]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT in this clinical scenario. DOTATATE PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of Ga-68-DOTATATE PET/CT in this clinical scenario. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen There is no relevant literature to support the use of In-111 somatostatin receptor scan with SPECT or SPECT/CT in this clinical scenario. There is no relevant literature that has assessed the performance of MRI without IV contrast specifically for this clinical scenario. Therefore, the committee recommendations on the use of MRI without IV contrast are based primarily on expert opinion. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. Liver Lesion-Initial Characterization Liver Lesion-Initial Characterization

Liver Lesion Initial Characterization. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. Liver Lesion-Initial Characterization US Abdomen In patients with a history of primary malignancy and indeterminate, subcentimeter focal liver lesions on CT, grayscale US is able to prove cystic nature of the lesion in 67% of cases [88]. US Abdomen with Contrast In patients with a history of primary malignancy and indeterminate, subcentimeter focal liver lesions on CT that were proven to be noncystic on grayscale US, CEUS correctly characterizes 95% of lesions overall, and 98% of metastases [88]. Compared with a baseline dual-phase contrast-enhanced CT, CEUS can detect 6.5 times more subcentimeter metastases [9]. CT of the abdomen with and without IV contrast is not recommended for this clinical scenario because there is no added value for unenhanced images. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT in this clinical scenario. DOTATATE PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of Ga-68-DOTATATE PET/CT in this clinical scenario. Octreotide Scan with SPECT or SPECT/CT Chest and Abdomen There is no relevant literature to support the use of In-111 somatostatin receptor scan with SPECT or SPECT/CT in this clinical scenario. There is no relevant literature that has assessed the performance of MRI without IV contrast specifically for this clinical scenario. Therefore, the committee recommendations on the use of MRI without IV contrast are based primarily on expert opinion. RBC Scan Abdomen and Pelvis There is no relevant literature to support the use of a Tc-99m RBC scan in this clinical scenario. Liver Spleen Scan There is no relevant literature to support the use of a Tc-99m sulfur colloid scan in this clinical scenario. Liver Lesion-Initial Characterization Liver Lesion-Initial Characterization

69472

acrac_69444_0

Urinary Tract Infection Child

Cystitis is a UTI limited to the bladder. Cystitis typically presents with localized symptoms of frequency, urgency, fever, and dysuria. Cystitis in the absence of pyelonephritis is usually not associated with long-term sequelae [4]. Acute pyelonephritis is infection of one or both kidneys. Pyelonephritis typically presents with systemic symptoms such as high fever, malaise, vomiting, abdominal or flank pain, and tenderness [2-5]. Pyelonephritis is diagnosed in children on the basis of the presence of pyuria and/or bacteriuria, fever, flank pain, or tenderness. Between 50% and 64% of children who have a febrile UTI are found to have defects on renal cortical scintigraphy indicating acute pyelonephritis [7]. Pyelonephritis can cause renal scarring, which is the most severe long-term sequela of UTI and can lead to accelerated nephrosclerosis, leading to hypertension and chronic renal failure [2-5]. The reported incidence of scarring in children after pyelonephritis varies widely in the literature. A systematic review showed that 15% (95% confidence interval, 11%-18%) of children had evidence of renal scarring after the first episode of UTI [7]. With the increased use of prenatal ultrasound (US), it was determined that many of the scars that had been attributed to pyelonephritis actually occur in utero and represent renal dysplasia [2-5]. Contrary to earlier studies suggesting that renal scarring secondary to pyelonephritis is the most common cause of chronic renal disease in children, it is now evident that the long-term risk is low [2-5]. The role of imaging is to guide treatment by identifying patients who are at high risk to develop recurrent UTIs or renal scarring. However, identification of children at risk is relevant only if there is effective treatment. Current management strategy to prevent UTIs and renal scarring is based on prophylactic antibiotics and selective surgical correction of vesicoureteral reflux (VUR).

Urinary Tract Infection Child. Cystitis is a UTI limited to the bladder. Cystitis typically presents with localized symptoms of frequency, urgency, fever, and dysuria. Cystitis in the absence of pyelonephritis is usually not associated with long-term sequelae [4]. Acute pyelonephritis is infection of one or both kidneys. Pyelonephritis typically presents with systemic symptoms such as high fever, malaise, vomiting, abdominal or flank pain, and tenderness [2-5]. Pyelonephritis is diagnosed in children on the basis of the presence of pyuria and/or bacteriuria, fever, flank pain, or tenderness. Between 50% and 64% of children who have a febrile UTI are found to have defects on renal cortical scintigraphy indicating acute pyelonephritis [7]. Pyelonephritis can cause renal scarring, which is the most severe long-term sequela of UTI and can lead to accelerated nephrosclerosis, leading to hypertension and chronic renal failure [2-5]. The reported incidence of scarring in children after pyelonephritis varies widely in the literature. A systematic review showed that 15% (95% confidence interval, 11%-18%) of children had evidence of renal scarring after the first episode of UTI [7]. With the increased use of prenatal ultrasound (US), it was determined that many of the scars that had been attributed to pyelonephritis actually occur in utero and represent renal dysplasia [2-5]. Contrary to earlier studies suggesting that renal scarring secondary to pyelonephritis is the most common cause of chronic renal disease in children, it is now evident that the long-term risk is low [2-5]. The role of imaging is to guide treatment by identifying patients who are at high risk to develop recurrent UTIs or renal scarring. However, identification of children at risk is relevant only if there is effective treatment. Current management strategy to prevent UTIs and renal scarring is based on prophylactic antibiotics and selective surgical correction of vesicoureteral reflux (VUR).

69444

acrac_69444_1

Urinary Tract Infection Child

UTI in a neonate or young infant requires special consideration. The prevalence of UTI in term neonates and young infants varies from 0.1% to 1%, with a predominance in the first 2 months of life in neonates and young infants AMAB [8-11]. The presentation of UTI is generally nonspecific, with symptoms similar to neonatal sepsis, and not all children will have fever. Concomitant bacteremia is common with UTI and was observed ranging from 4% to 36.4% [5,8-11]. Neonates with UTI have a high incidence of urinary anomalies; the most common is VUR [8,10- 12]. Reprint requests to: [email protected] Urinary Tract Infection-Child tract UTI, or 1 episode of UTI with acute pyelonephritis/upper tract UTI plus 1 or more episodes of UTI with cystitis/lower tract UTI, or 3 or more episodes of UTI with cystitis/lower tract UTI [13]. Upper tract refers to the kidneys and ureters, and lower tract is distal to the ureters. Special Imaging Considerations Voiding urosonography (VUS) is a safe and accurate method to evaluate for VUR. The bladder is filled with a solution containing microbubbles that appear echogenic by US. CT urography (CTU) is an imaging study that is tailored to improve visualization of both the upper and lower urinary tracts. There is variability in the specific parameters, but it usually involves unenhanced images followed by intravenous (IV) contrast-enhanced images, including nephrographic and excretory phases acquired at least 5 minutes after contrast injection. Alternatively, a split-bolus technique uses an initial loading dose of IV contrast and then obtains a combined nephrographic-excretory phase after a second IV contrast dose; some sites include arterial phase. CTU should use thin-slice acquisition. Reconstruction methods commonly include maximum intensity projection or 3-D volume rendering. For the purposes of this document, we make a distinction between CTU and CT abdomen and pelvis without and with IV contrast.

Urinary Tract Infection Child. UTI in a neonate or young infant requires special consideration. The prevalence of UTI in term neonates and young infants varies from 0.1% to 1%, with a predominance in the first 2 months of life in neonates and young infants AMAB [8-11]. The presentation of UTI is generally nonspecific, with symptoms similar to neonatal sepsis, and not all children will have fever. Concomitant bacteremia is common with UTI and was observed ranging from 4% to 36.4% [5,8-11]. Neonates with UTI have a high incidence of urinary anomalies; the most common is VUR [8,10- 12]. Reprint requests to: [email protected] Urinary Tract Infection-Child tract UTI, or 1 episode of UTI with acute pyelonephritis/upper tract UTI plus 1 or more episodes of UTI with cystitis/lower tract UTI, or 3 or more episodes of UTI with cystitis/lower tract UTI [13]. Upper tract refers to the kidneys and ureters, and lower tract is distal to the ureters. Special Imaging Considerations Voiding urosonography (VUS) is a safe and accurate method to evaluate for VUR. The bladder is filled with a solution containing microbubbles that appear echogenic by US. CT urography (CTU) is an imaging study that is tailored to improve visualization of both the upper and lower urinary tracts. There is variability in the specific parameters, but it usually involves unenhanced images followed by intravenous (IV) contrast-enhanced images, including nephrographic and excretory phases acquired at least 5 minutes after contrast injection. Alternatively, a split-bolus technique uses an initial loading dose of IV contrast and then obtains a combined nephrographic-excretory phase after a second IV contrast dose; some sites include arterial phase. CTU should use thin-slice acquisition. Reconstruction methods commonly include maximum intensity projection or 3-D volume rendering. For the purposes of this document, we make a distinction between CTU and CT abdomen and pelvis without and with IV contrast.

69444

acrac_69444_2

Urinary Tract Infection Child

CT abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts and without both the nonenhanced and excretory phases. MR urography (MRU) is also tailored to improve imaging of the urinary system. Unenhanced MRU relies upon heavily T2-weighted imaging of the intrinsic high signal intensity from urine for evaluation of the urinary tract. IV contrast is administered to provide additional information regarding obstruction, urothelial thickening, focal lesions, and stones. A contrast-enhanced T1-weighted series should include corticomedullary, nephrographic, and excretory phase. Thin-slice acquisition and multiplanar imaging should be obtained. For the purposes of this document, we make a distinction between MRU and MRI abdomen and pelvis without and with IV contrast. MRI abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts, without both the precontrast and excretory phases, and without heavily T2-weighted images of the urinary tract. OR Discussion of Procedures by Variant Variant 1: Child assigned male at birth (AMAB). Younger than 2 months of age. First febrile urinary tract infection with appropriate response to medical management. Initial imaging. CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI.

Urinary Tract Infection Child. CT abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts and without both the nonenhanced and excretory phases. MR urography (MRU) is also tailored to improve imaging of the urinary system. Unenhanced MRU relies upon heavily T2-weighted imaging of the intrinsic high signal intensity from urine for evaluation of the urinary tract. IV contrast is administered to provide additional information regarding obstruction, urothelial thickening, focal lesions, and stones. A contrast-enhanced T1-weighted series should include corticomedullary, nephrographic, and excretory phase. Thin-slice acquisition and multiplanar imaging should be obtained. For the purposes of this document, we make a distinction between MRU and MRI abdomen and pelvis without and with IV contrast. MRI abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts, without both the precontrast and excretory phases, and without heavily T2-weighted images of the urinary tract. OR Discussion of Procedures by Variant Variant 1: Child assigned male at birth (AMAB). Younger than 2 months of age. First febrile urinary tract infection with appropriate response to medical management. Initial imaging. CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI.

69444

acrac_69444_3

Urinary Tract Infection Child

CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. Urinary Tract Infection-Child DMSA Renal Scan A Tc-99m dimercaptosuccinic acid (DMSA) scan can be done for the initial imaging, close to the time of febrile UTI to evaluate for the presence of pyelonephritis. If the DMSA scan is normal, voiding cystourethrography (VCUG) may be avoided in >50% of individuals [14]. Tc-99m DMSA has a good image quality and is a desirable agent for renal cortical scintigraphy, especially in small infants, in patients with poorly functioning kidneys, and when other studies have identified dilated uropathy or high-grade VUR [15]. The UK National Institute for Health and Care Excellence (NICE) guidelines do not recommend DMSA for infants <6 months of age with first febrile UTI who respond well to treatment within 48 hours [16]. Fluoroscopy Voiding Cystourethrography Literature on VCUG has mixed recommendations. Fluoroscopic VCUG has been shown to detect VUR in newborn children AMAB even if US is normal [8-11]. A finding of VUR, especially high-grade VUR, may lead to a change in management [9]. VUR is more commonly detected in children AMAB compared with children AFAB [17]. In addition, one of the primary concerns in young infants AMAB is diagnosing posterior urethral valves [9]. The NICE guidelines do not recommend VCUG for infants AMAB <6 months of age with first febrile UTI who respond well to treatment within 48 hours. If there is poor urine flow or if there is a family history of VUR, VCUG may be helpful if there is an abnormal kidney US study [16]. Others advocate performing routine VCUG studies in all newborns AMAB [9].

Urinary Tract Infection Child. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. Urinary Tract Infection-Child DMSA Renal Scan A Tc-99m dimercaptosuccinic acid (DMSA) scan can be done for the initial imaging, close to the time of febrile UTI to evaluate for the presence of pyelonephritis. If the DMSA scan is normal, voiding cystourethrography (VCUG) may be avoided in >50% of individuals [14]. Tc-99m DMSA has a good image quality and is a desirable agent for renal cortical scintigraphy, especially in small infants, in patients with poorly functioning kidneys, and when other studies have identified dilated uropathy or high-grade VUR [15]. The UK National Institute for Health and Care Excellence (NICE) guidelines do not recommend DMSA for infants <6 months of age with first febrile UTI who respond well to treatment within 48 hours [16]. Fluoroscopy Voiding Cystourethrography Literature on VCUG has mixed recommendations. Fluoroscopic VCUG has been shown to detect VUR in newborn children AMAB even if US is normal [8-11]. A finding of VUR, especially high-grade VUR, may lead to a change in management [9]. VUR is more commonly detected in children AMAB compared with children AFAB [17]. In addition, one of the primary concerns in young infants AMAB is diagnosing posterior urethral valves [9]. The NICE guidelines do not recommend VCUG for infants AMAB <6 months of age with first febrile UTI who respond well to treatment within 48 hours. If there is poor urine flow or if there is a family history of VUR, VCUG may be helpful if there is an abnormal kidney US study [16]. Others advocate performing routine VCUG studies in all newborns AMAB [9].

69444

acrac_69444_4

Urinary Tract Infection Child

Furthermore, recent data have shown that in children <3 months of age with first febrile UTI, the presence of E coli in urine, and normal renal and bladder US, VCUG can be safely avoided [18]. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. Nuclear Medicine Cystography There is no relevant literature to support the use of nuclear medicine cystography in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. There is good correlation between nuclear medicine cystography and VCUG for the detection of reflux [19]. The nuclear cystogram does not allow for urethral assessment in a infant AMAB [20]. US Kidneys and Bladder In a child AMAB <2 months of age, there is increased incidence of sepsis and renal anomalies associated with UTIs and increased rate of hospitalization. Therefore, the potential benefit of imaging in children <2 months of age is greater than in older children. However, there is less convincing evidence for the benefit of imaging based on outcome [8-11,21]. Hydronephrosis is the most frequent abnormality, found in 45% of neonates with UTI [9]. Postnatal US prior to 2 months of age is typically performed even if the prenatal US was normal.

Urinary Tract Infection Child. Furthermore, recent data have shown that in children <3 months of age with first febrile UTI, the presence of E coli in urine, and normal renal and bladder US, VCUG can be safely avoided [18]. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. Nuclear Medicine Cystography There is no relevant literature to support the use of nuclear medicine cystography in the evaluation of a child AMAB <2 months of age for the initial imaging of a first febrile UTI. There is good correlation between nuclear medicine cystography and VCUG for the detection of reflux [19]. The nuclear cystogram does not allow for urethral assessment in a infant AMAB [20]. US Kidneys and Bladder In a child AMAB <2 months of age, there is increased incidence of sepsis and renal anomalies associated with UTIs and increased rate of hospitalization. Therefore, the potential benefit of imaging in children <2 months of age is greater than in older children. However, there is less convincing evidence for the benefit of imaging based on outcome [8-11,21]. Hydronephrosis is the most frequent abnormality, found in 45% of neonates with UTI [9]. Postnatal US prior to 2 months of age is typically performed even if the prenatal US was normal.

69444

acrac_69444_5

Urinary Tract Infection Child

The NICE guidelines for UTI recommend US in evaluation of UTI in children <6 months of age within 6 weeks of the UTI if typical infection or during the acute infection if an atypical infection [16]. In the study by Goldman et al [9] on newborn AMAB with UTI, 8 of 12 children with abnormal postnatal US had a normal intrauterine US; 1 patient had posterior urethral valves, and 4 patients had grades III and IV VUR. The main limitations of US are the detection of pyelonephritis, scarring, and VUR. In a study by Chang et al [22] for evaluation of young infants (<3 months of age) with bacteremic UTI, US kidneys and bladder and fluoroscopic VCUG abnormalities were common, and the authors did not refer to any special imaging considerations for bacteremia in imaging decisions for otherwise well- appearing young infants with UTI. US has a high specificity (97.2%) for the detection of findings suggestive of VUR in children after the first UTI [23]. Sensitivity of US for the detection of findings suggestive of high-grade VUR is markedly improved when uroepithelial thickening is considered [24]. The main limitation of US is the low sensitivity (76.5%) for detecting VUR and renal scarring [25-31]. Voiding Urosonography VUS is an alternative to VCUG for the evaluation of VUR in children, with a comparable sensitivity and specificity ranging from 80% to 100% and 77.5% to 98%, respectively [32-39]. The diagnostic accuracy of VUS compared Variant 2: Child assigned female at birth (AFAB). First febrile urinary tract infection with appropriate response to medical management. Initial imaging. CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI.

Urinary Tract Infection Child. The NICE guidelines for UTI recommend US in evaluation of UTI in children <6 months of age within 6 weeks of the UTI if typical infection or during the acute infection if an atypical infection [16]. In the study by Goldman et al [9] on newborn AMAB with UTI, 8 of 12 children with abnormal postnatal US had a normal intrauterine US; 1 patient had posterior urethral valves, and 4 patients had grades III and IV VUR. The main limitations of US are the detection of pyelonephritis, scarring, and VUR. In a study by Chang et al [22] for evaluation of young infants (<3 months of age) with bacteremic UTI, US kidneys and bladder and fluoroscopic VCUG abnormalities were common, and the authors did not refer to any special imaging considerations for bacteremia in imaging decisions for otherwise well- appearing young infants with UTI. US has a high specificity (97.2%) for the detection of findings suggestive of VUR in children after the first UTI [23]. Sensitivity of US for the detection of findings suggestive of high-grade VUR is markedly improved when uroepithelial thickening is considered [24]. The main limitation of US is the low sensitivity (76.5%) for detecting VUR and renal scarring [25-31]. Voiding Urosonography VUS is an alternative to VCUG for the evaluation of VUR in children, with a comparable sensitivity and specificity ranging from 80% to 100% and 77.5% to 98%, respectively [32-39]. The diagnostic accuracy of VUS compared Variant 2: Child assigned female at birth (AFAB). First febrile urinary tract infection with appropriate response to medical management. Initial imaging. CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI.

69444

acrac_69444_6

Urinary Tract Infection Child

CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. DMSA Renal Scan A Tc-99m DMSA scan can be done for initial imaging, close to the time of febrile UTI, to evaluate for the presence of pyelonephritis. This top-down approach has been suggested in literature. If the DMSA scan is normal, VCUG may be avoided in more than 50% of individuals [14]. Tc-99m DMSA has a good image quality and is a desirable agent for renal cortical scintigraphy, especially in small infants, in patients with poorly functioning kidneys, and when other studies have identified dilated uropathy or high-grade VUR [15]. The NICE guidelines do not recommend DMSA for infants <6 months of age with first febrile UTI who respond well to treatment within 48 hours, but they do recommend DMSA for atypical or recurrent UTI [16]. Fluoroscopy Voiding Cystourethrography A finding of VUR, especially high-grade VUR, may lead to a change in management [9]. The NICE guidelines do not recommend VCUG for infants AFAB <6 months of age with first febrile UTI who respond well to treatment within 48 hours. Furthermore, recent data has shown that in children <3 months of age with first febrile UTI, the presence of E coli in urine, and normal renal and bladder US, VCUG can be safely avoided [18].

Urinary Tract Infection Child. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. DMSA Renal Scan A Tc-99m DMSA scan can be done for initial imaging, close to the time of febrile UTI, to evaluate for the presence of pyelonephritis. This top-down approach has been suggested in literature. If the DMSA scan is normal, VCUG may be avoided in more than 50% of individuals [14]. Tc-99m DMSA has a good image quality and is a desirable agent for renal cortical scintigraphy, especially in small infants, in patients with poorly functioning kidneys, and when other studies have identified dilated uropathy or high-grade VUR [15]. The NICE guidelines do not recommend DMSA for infants <6 months of age with first febrile UTI who respond well to treatment within 48 hours, but they do recommend DMSA for atypical or recurrent UTI [16]. Fluoroscopy Voiding Cystourethrography A finding of VUR, especially high-grade VUR, may lead to a change in management [9]. The NICE guidelines do not recommend VCUG for infants AFAB <6 months of age with first febrile UTI who respond well to treatment within 48 hours. Furthermore, recent data has shown that in children <3 months of age with first febrile UTI, the presence of E coli in urine, and normal renal and bladder US, VCUG can be safely avoided [18].

69444

acrac_69444_7

Urinary Tract Infection Child

In patients AFAB, there is usually less of a need for detailed anatomic evaluation of the urethra, and radionuclide cystography can be performed as an alternative to VCUG [42]. However, fluoroscopic VCUG may still be a useful study to perform based on consensus opinion derived from common practice. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. Nuclear Medicine Cystography There is good correlation between nuclear medicine cystography and VCUG for the detection of reflux [19]. For more information, please see the fluoroscopic VCUG section. In patients AFAB, there is usually less of a need for detailed anatomic evaluation of the urethra, and radionuclide cystography can be performed instead of VCUG [42]. Urinary Tract Infection-Child The literature in this patient population is evolving with a focus on other modalities such as VUS and fluoroscopy VCUG. It should be noted that the primary evidence supporting use of nuclear cystography is generally older than that of other modalities. US Kidneys and Bladder In patients AFAB <2 months of age, there is an increased incidence of sepsis and renal anomalies associated with UTIs and an increased rate of hospitalization. Therefore, the potential benefit in children <2 months of age is greater than in older children. However, there is less convincing evidence for the benefit of imaging based on outcome [8- 11,21].

Urinary Tract Infection Child. In patients AFAB, there is usually less of a need for detailed anatomic evaluation of the urethra, and radionuclide cystography can be performed as an alternative to VCUG [42]. However, fluoroscopic VCUG may still be a useful study to perform based on consensus opinion derived from common practice. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child AFAB <2 months of age for the initial imaging of a first febrile UTI. Nuclear Medicine Cystography There is good correlation between nuclear medicine cystography and VCUG for the detection of reflux [19]. For more information, please see the fluoroscopic VCUG section. In patients AFAB, there is usually less of a need for detailed anatomic evaluation of the urethra, and radionuclide cystography can be performed instead of VCUG [42]. Urinary Tract Infection-Child The literature in this patient population is evolving with a focus on other modalities such as VUS and fluoroscopy VCUG. It should be noted that the primary evidence supporting use of nuclear cystography is generally older than that of other modalities. US Kidneys and Bladder In patients AFAB <2 months of age, there is an increased incidence of sepsis and renal anomalies associated with UTIs and an increased rate of hospitalization. Therefore, the potential benefit in children <2 months of age is greater than in older children. However, there is less convincing evidence for the benefit of imaging based on outcome [8- 11,21].

69444

acrac_69444_8

Urinary Tract Infection Child

Hydronephrosis is the most frequent abnormality, found in 45% of neonates with UTI [9]. Postnatal US prior to 2 months of age is typically performed even if the prenatal US was normal. The NICE guidelines for UTI recommend US in evaluation of UTI in children <6 months of age within 6 weeks of the UTI if typical infection or during the acute infection if an atypical infection [16]. As discussed earlier, the main limitations of US are the detection of pyelonephritis, scarring, and VUR. In a study by Chang et al [22] for evaluation of young infants (<3 months of age) with bacteremic UTI, US kidneys and bladder and fluoroscopic VCUG abnormalities were common, and the authors did not refer to any special imaging considerations for bacteremia in imaging decisions for otherwise well-appearing young infants with UTI. Sensitivity of US for the detection of high-grade VUR is markedly improved when uroepithelial thickening is considered [24]. The main limitation of US is the low sensitivity (76.5%) for detecting VUR and renal scarring [25-31]. Variant 3: Child. 2 months to 6 years of age. First febrile urinary tract infection with appropriate response to medical management. Initial imaging. Prospective studies in children between the ages of 2 months and 6 years with UTIs were done to evaluate the effect of therapy [6,43,44]. There is limited evidence to support routine imaging of uncomplicated UTIs, and optimal imaging is controversial [2,5,43,45]. Currently there are 2 main methods for evaluating children with UTIs: the bottom-up approach [2], which focuses on detection of VUR, and the top-down approach [2,5,16], which focuses on the diagnosis of acute pyelonephritis and renal scarring [2,5]. DMSA followed by cystourethrography if DMSA renal scan suggests pyelonephritis is the top-down approach. The potential benefit of this approach is a decrease in the number of cystourethrography studies.

Urinary Tract Infection Child. Hydronephrosis is the most frequent abnormality, found in 45% of neonates with UTI [9]. Postnatal US prior to 2 months of age is typically performed even if the prenatal US was normal. The NICE guidelines for UTI recommend US in evaluation of UTI in children <6 months of age within 6 weeks of the UTI if typical infection or during the acute infection if an atypical infection [16]. As discussed earlier, the main limitations of US are the detection of pyelonephritis, scarring, and VUR. In a study by Chang et al [22] for evaluation of young infants (<3 months of age) with bacteremic UTI, US kidneys and bladder and fluoroscopic VCUG abnormalities were common, and the authors did not refer to any special imaging considerations for bacteremia in imaging decisions for otherwise well-appearing young infants with UTI. Sensitivity of US for the detection of high-grade VUR is markedly improved when uroepithelial thickening is considered [24]. The main limitation of US is the low sensitivity (76.5%) for detecting VUR and renal scarring [25-31]. Variant 3: Child. 2 months to 6 years of age. First febrile urinary tract infection with appropriate response to medical management. Initial imaging. Prospective studies in children between the ages of 2 months and 6 years with UTIs were done to evaluate the effect of therapy [6,43,44]. There is limited evidence to support routine imaging of uncomplicated UTIs, and optimal imaging is controversial [2,5,43,45]. Currently there are 2 main methods for evaluating children with UTIs: the bottom-up approach [2], which focuses on detection of VUR, and the top-down approach [2,5,16], which focuses on the diagnosis of acute pyelonephritis and renal scarring [2,5]. DMSA followed by cystourethrography if DMSA renal scan suggests pyelonephritis is the top-down approach. The potential benefit of this approach is a decrease in the number of cystourethrography studies.

69444

acrac_69444_9

Urinary Tract Infection Child

CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. DMSA Renal Scan Tc-99m DMSA is a sensitive (90%) and specific (95%) test for detecting pyelonephritis [46]. The NICE guidelines do not suggest DMSA renal scan if the patient responds well to treatment within 48 hours. A delayed DMSA renal scan (4-6 months) to evaluate for renal scarring in high-risk patients with atypical or recurrent UTI is recommended Urinary Tract Infection-Child [16]. Evidence of acute pyelonephritis is detected by DMSA in children with UTIs in approximately 50% to 80% of cases [47-52]. However, short-term studies have demonstrated that many of these abnormalities resolve over time, irrespective of whether a prophylactic antibiotic was used [53-55]. This suggests little benefit in using renal cortical scintigraphy after the first episode of UTI [5]. Furthermore, the high incidence of pyelonephritis identified on DMSA suggests that performing DMSA will not change the need to perform VCUG in many patients.

Urinary Tract Infection Child. CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. DMSA Renal Scan Tc-99m DMSA is a sensitive (90%) and specific (95%) test for detecting pyelonephritis [46]. The NICE guidelines do not suggest DMSA renal scan if the patient responds well to treatment within 48 hours. A delayed DMSA renal scan (4-6 months) to evaluate for renal scarring in high-risk patients with atypical or recurrent UTI is recommended Urinary Tract Infection-Child [16]. Evidence of acute pyelonephritis is detected by DMSA in children with UTIs in approximately 50% to 80% of cases [47-52]. However, short-term studies have demonstrated that many of these abnormalities resolve over time, irrespective of whether a prophylactic antibiotic was used [53-55]. This suggests little benefit in using renal cortical scintigraphy after the first episode of UTI [5]. Furthermore, the high incidence of pyelonephritis identified on DMSA suggests that performing DMSA will not change the need to perform VCUG in many patients.

69444

acrac_69444_10

Urinary Tract Infection Child

There is conflicting evidence on the sensitivity of renal cortical scintigraphy and the top-down approach in the detection of sequela of VUR [45,56,57]. In a randomized controlled study comparing oral versus IV antibiotic administration, 308 patients who had Tc-99m DMSA were evaluated. The sensitivity of this top-down approach for VUR detection was 70%, with specificity of 42% [45]. A meta-analysis on the use of DMSA in acute UTI yielded a sensitivity and specificity of 79% and 53%, respectively, for grades 3 to 5 VUR. There was marked statistical heterogeneity between the studies. The authors concluded that acute-phase DMSA renal scanning is not useful as a replacement for VCUG in the evaluation of young children with a first febrile UTI [56]. Fluoroscopy Voiding Cystourethrography The Randomized Intervention for Children With Vesicoureteral Reflux study, which enrolled 607 children, 2 months to 6 years of age with any grade of VUR, demonstrated that 2 years of prophylactic antibiotics in children with VUR decreased the incidence of recurrent UTIs by half (number needed to treat for 2 years was 8) [58]. Patients with high-grade VUR (grades III and IV) are more likely to have recurrent UTIs and scarring [7,43,50,58-61] and may benefit even more from prophylactic antibiotics. The Swedish study randomly assigned 203 children, 12 to 23 months of age, with dilated (grade III or IV) VUR and demonstrated benefit only in patients AFAB who received either prophylactic antibiotics or endoscopic treatment in decreasing recurrent UTI (number needed to treat for 2 years, 2.5 and 3, respectively) [62]. Patients AFAB who received antimicrobial prophylaxis had the lowest incidence of renal scarring (number needed to treat for 2 years was 5) [62]. The NICE guidelines do not recommend VCUG for patients from 6 months to 3 years of age with first febrile UTI who respond well to treatment within 48 hours and have a normal renal and bladder US study, normal urine flow, and no family history of VUR.

Urinary Tract Infection Child. There is conflicting evidence on the sensitivity of renal cortical scintigraphy and the top-down approach in the detection of sequela of VUR [45,56,57]. In a randomized controlled study comparing oral versus IV antibiotic administration, 308 patients who had Tc-99m DMSA were evaluated. The sensitivity of this top-down approach for VUR detection was 70%, with specificity of 42% [45]. A meta-analysis on the use of DMSA in acute UTI yielded a sensitivity and specificity of 79% and 53%, respectively, for grades 3 to 5 VUR. There was marked statistical heterogeneity between the studies. The authors concluded that acute-phase DMSA renal scanning is not useful as a replacement for VCUG in the evaluation of young children with a first febrile UTI [56]. Fluoroscopy Voiding Cystourethrography The Randomized Intervention for Children With Vesicoureteral Reflux study, which enrolled 607 children, 2 months to 6 years of age with any grade of VUR, demonstrated that 2 years of prophylactic antibiotics in children with VUR decreased the incidence of recurrent UTIs by half (number needed to treat for 2 years was 8) [58]. Patients with high-grade VUR (grades III and IV) are more likely to have recurrent UTIs and scarring [7,43,50,58-61] and may benefit even more from prophylactic antibiotics. The Swedish study randomly assigned 203 children, 12 to 23 months of age, with dilated (grade III or IV) VUR and demonstrated benefit only in patients AFAB who received either prophylactic antibiotics or endoscopic treatment in decreasing recurrent UTI (number needed to treat for 2 years, 2.5 and 3, respectively) [62]. Patients AFAB who received antimicrobial prophylaxis had the lowest incidence of renal scarring (number needed to treat for 2 years was 5) [62]. The NICE guidelines do not recommend VCUG for patients from 6 months to 3 years of age with first febrile UTI who respond well to treatment within 48 hours and have a normal renal and bladder US study, normal urine flow, and no family history of VUR.

69444

acrac_69444_11

Urinary Tract Infection Child

However, VCUG is recommended for patients with a family history of VUR [16]. The NICE guidelines do not recommend VCUG for patients >3 years of age with first febrile UTI. The AAP guidelines suggest that VCUG should not be performed routinely after the first febrile UTI for patients 2 to 24 months of age but that VCUG is indicated if the renal and bladder US reveals hydronephrosis, scarring, or other findings that would suggest either high-grade VUR or obstructive uropathy. Furthermore, VCUG may be indicated in other atypical or complex clinical circumstances [41]. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. Nuclear Medicine Cystography Good correlation has been shown between nuclear medicine cystography and VCUG for the detection of VUR [19]. Unlike in children AMAB, detailed urethral assessment in children AFAB is less necessary, so radionuclide cystography can be performed as an alternative for VCUG in patients AFAB [42,48]. A finding of VUR, especially high-grade VUR, may lead to a change in management [9]. Nuclear medicine cystography may reveal VUR despite a normal VCUG in children with recurrent febrile UTI [63]. For more information, please see the fluoroscopic VCUG section. US Kidneys and Bladder The main benefit of US is for the detection of underlying congenital renal anomalies [1,16].

Urinary Tract Infection Child. However, VCUG is recommended for patients with a family history of VUR [16]. The NICE guidelines do not recommend VCUG for patients >3 years of age with first febrile UTI. The AAP guidelines suggest that VCUG should not be performed routinely after the first febrile UTI for patients 2 to 24 months of age but that VCUG is indicated if the renal and bladder US reveals hydronephrosis, scarring, or other findings that would suggest either high-grade VUR or obstructive uropathy. Furthermore, VCUG may be indicated in other atypical or complex clinical circumstances [41]. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child 2 months to 6 years of age for the initial imaging of a first febrile UTI. Nuclear Medicine Cystography Good correlation has been shown between nuclear medicine cystography and VCUG for the detection of VUR [19]. Unlike in children AMAB, detailed urethral assessment in children AFAB is less necessary, so radionuclide cystography can be performed as an alternative for VCUG in patients AFAB [42,48]. A finding of VUR, especially high-grade VUR, may lead to a change in management [9]. Nuclear medicine cystography may reveal VUR despite a normal VCUG in children with recurrent febrile UTI [63]. For more information, please see the fluoroscopic VCUG section. US Kidneys and Bladder The main benefit of US is for the detection of underlying congenital renal anomalies [1,16].

69444

acrac_69444_12

Urinary Tract Infection Child

The potential harm of using US as the only imaging for UTI is the poor sensitivity for VUR and pyelonephritis/scarring [25-30,64]. There are limited data showing inconsistent results on the sensitivity of US in the detection of dilated VUR [65,66]. Grayscale US identifies approximately 25% of the patients with acute pyelonephritis and approximately 40% of the patients with chronic parenchymal scarring [29,31,67-72]. Urinary Tract Infection-Child In a retrospective study of 2,259 children <5 years of age, sensitivity of US was related to criteria for the definition of a normal study. With the use of the most relaxed criteria (25% abnormal), US had a sensitivity of 28% (specificity of 77%), and with the most stringent criteria (4% abnormal), US had a sensitivity of 5% (specificity of 97%) [31]. Assuming a 40% prevalence of VUR and a 20% recurrent rate of UTIs in 100 children who have US, up to 11 children will have positive US studies that will be followed by a VCUG study, of which 8 will be positive for VUR. Two years of a prophylactic antibiotic will decrease recurrent UTIs from up to 2 children to 1 child. This means that 1 child will benefit from US and an additional 3 children that may benefit from prophylactic antibiotic will not be treated. In addition, with the increased use of prenatal US screening, the yield of detection of unknown renal abnormalities in children with UTIs has decreased [73]. A few studies with small series of children suggest good correlation between power Doppler and Tc-99m DMSA for pyelonephritis [74,75]. Other studies, however, demonstrated low sensitivity for pyelonephritis and low prediction for development of renal scarring [49,76,77]. Therefore, the use of power Doppler as a replacement for DMSA is not useful [26,49,76]. The NICE guidelines for UTI do not recommend US in evaluation of UTI in children >6 months of age if typical infection [16]. The AAP guidelines recommend US for children with a febrile UTI from ages 2 to 24 months [41].

Urinary Tract Infection Child. The potential harm of using US as the only imaging for UTI is the poor sensitivity for VUR and pyelonephritis/scarring [25-30,64]. There are limited data showing inconsistent results on the sensitivity of US in the detection of dilated VUR [65,66]. Grayscale US identifies approximately 25% of the patients with acute pyelonephritis and approximately 40% of the patients with chronic parenchymal scarring [29,31,67-72]. Urinary Tract Infection-Child In a retrospective study of 2,259 children <5 years of age, sensitivity of US was related to criteria for the definition of a normal study. With the use of the most relaxed criteria (25% abnormal), US had a sensitivity of 28% (specificity of 77%), and with the most stringent criteria (4% abnormal), US had a sensitivity of 5% (specificity of 97%) [31]. Assuming a 40% prevalence of VUR and a 20% recurrent rate of UTIs in 100 children who have US, up to 11 children will have positive US studies that will be followed by a VCUG study, of which 8 will be positive for VUR. Two years of a prophylactic antibiotic will decrease recurrent UTIs from up to 2 children to 1 child. This means that 1 child will benefit from US and an additional 3 children that may benefit from prophylactic antibiotic will not be treated. In addition, with the increased use of prenatal US screening, the yield of detection of unknown renal abnormalities in children with UTIs has decreased [73]. A few studies with small series of children suggest good correlation between power Doppler and Tc-99m DMSA for pyelonephritis [74,75]. Other studies, however, demonstrated low sensitivity for pyelonephritis and low prediction for development of renal scarring [49,76,77]. Therefore, the use of power Doppler as a replacement for DMSA is not useful [26,49,76]. The NICE guidelines for UTI do not recommend US in evaluation of UTI in children >6 months of age if typical infection [16]. The AAP guidelines recommend US for children with a febrile UTI from ages 2 to 24 months [41].

69444

acrac_69444_13

Urinary Tract Infection Child

Variant 4: Child. Older than 6 years of age. First febrile urinary tract infection with appropriate response to medical management. Initial imaging. The incidence of new-onset UTI in children >6 years of age is low and often associated with behavioral abnormalities, dysfunctional elimination syndrome, or initiation of sexual intercourse in adolescents [78,79]. Patients AFAB are affected more often than patients AMAB [78]. The likelihood of detection of a previously unknown underlying renal anomaly is low [79]. There is no evidence to support any routine imaging in the first UTI in this group of patients. CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. DMSA Renal Scan The NICE guidelines do not recommend DMSA renal scan for patients >6 years of age with first febrile UTI [16]. Fluoroscopy Voiding Cystourethrography The NICE guidelines do not recommend VCUG for patients >6 years of age with first febrile UTI [16]. Urinary Tract Infection-Child

Urinary Tract Infection Child. Variant 4: Child. Older than 6 years of age. First febrile urinary tract infection with appropriate response to medical management. Initial imaging. The incidence of new-onset UTI in children >6 years of age is low and often associated with behavioral abnormalities, dysfunctional elimination syndrome, or initiation of sexual intercourse in adolescents [78,79]. Patients AFAB are affected more often than patients AMAB [78]. The likelihood of detection of a previously unknown underlying renal anomaly is low [79]. There is no evidence to support any routine imaging in the first UTI in this group of patients. CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. DMSA Renal Scan The NICE guidelines do not recommend DMSA renal scan for patients >6 years of age with first febrile UTI [16]. Fluoroscopy Voiding Cystourethrography The NICE guidelines do not recommend VCUG for patients >6 years of age with first febrile UTI [16]. Urinary Tract Infection-Child

69444

acrac_69444_14

Urinary Tract Infection Child

MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. Nuclear Medicine Cystography The NICE guidelines do not recommend cystography for patients >6 years of age with first febrile UTI [16]. Voiding Urosonography The NICE guidelines do not recommend VUS for patients >6 years of age with first febrile UTI [16]. However, VUS may be a useful study to perform based on consensus opinion. Variant 5: Child. Atypical or recurrent febrile urinary tract infections. Initial imaging. CT Abdomen and Pelvis With IV Contrast An IV contrast-enhanced CT scan can be performed selectively when there is suspicion for complications, such as renal abscess or xanthogranulomatous pyelonephritis [80-83]. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child with atypical or recurrent febrile UTI for the initial imaging. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging.

Urinary Tract Infection Child. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child >6 years of age for the initial imaging of a first febrile UTI with appropriate response to medical management. Nuclear Medicine Cystography The NICE guidelines do not recommend cystography for patients >6 years of age with first febrile UTI [16]. Voiding Urosonography The NICE guidelines do not recommend VUS for patients >6 years of age with first febrile UTI [16]. However, VUS may be a useful study to perform based on consensus opinion. Variant 5: Child. Atypical or recurrent febrile urinary tract infections. Initial imaging. CT Abdomen and Pelvis With IV Contrast An IV contrast-enhanced CT scan can be performed selectively when there is suspicion for complications, such as renal abscess or xanthogranulomatous pyelonephritis [80-83]. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child with atypical or recurrent febrile UTI for the initial imaging. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging.

69444

acrac_69444_15

Urinary Tract Infection Child

CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging. DMSA Renal Scan A DMSA renal scan may have limited benefit in patients with VUR and atypical, complicated, or recurrent UTIs. A normal DMSA scan in patients with recurrent infections may exclude high-grade reflux on VCUG and thus direct toward antibiotic treatment without the need for invasive VCUG. The NICE guidelines recommend DMSA renal scan 4 to 6 months after atypical or recurrent infection (<3 years) and for recurrent infection (>3 years) in children [83]. The literature in this patient population is evolving with a focus on other modalities such as VUS and fluoroscopy VCUG. It should be noted that the primary evidence supporting use of DMSA renal scan is generally older than that of other modalities. Fluoroscopy Voiding Cystourethrography Children with recurrent UTIs have an increased prevalence of VUR [43]. Based on multiple studies in a pooled cohort of infants after first UTI and recurrent UTI, the frequency of VUR increases from 35% to 74%, with increased risk for renal scarring with each UTI [1]. A finding of VUR without dilatation of urinary tract may lead to antibiotic prevention treatment, and a finding of dilated VUR may lead to endoscopic or surgical treatment. VCUG is routinely performed for children <6 months of age with atypical UTI and from 6 months to 3 years of age with atypical UTI and abnormalities on renal and bladder US, poor urine flow, or family history of VUR as per the NICE guidelines Urinary Tract Infection-Child [83]. VCUG is not recommended by NICE guidelines for children >3 years of age with UTI, even if atypical or recurrent UTI [16]. The AAP guidelines suggest VCUG for children 2 to 24 months of age after the second febrile UTI and after the first for patients with abnormalities on renal and bladder US [41].

Urinary Tract Infection Child. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging. DMSA Renal Scan A DMSA renal scan may have limited benefit in patients with VUR and atypical, complicated, or recurrent UTIs. A normal DMSA scan in patients with recurrent infections may exclude high-grade reflux on VCUG and thus direct toward antibiotic treatment without the need for invasive VCUG. The NICE guidelines recommend DMSA renal scan 4 to 6 months after atypical or recurrent infection (<3 years) and for recurrent infection (>3 years) in children [83]. The literature in this patient population is evolving with a focus on other modalities such as VUS and fluoroscopy VCUG. It should be noted that the primary evidence supporting use of DMSA renal scan is generally older than that of other modalities. Fluoroscopy Voiding Cystourethrography Children with recurrent UTIs have an increased prevalence of VUR [43]. Based on multiple studies in a pooled cohort of infants after first UTI and recurrent UTI, the frequency of VUR increases from 35% to 74%, with increased risk for renal scarring with each UTI [1]. A finding of VUR without dilatation of urinary tract may lead to antibiotic prevention treatment, and a finding of dilated VUR may lead to endoscopic or surgical treatment. VCUG is routinely performed for children <6 months of age with atypical UTI and from 6 months to 3 years of age with atypical UTI and abnormalities on renal and bladder US, poor urine flow, or family history of VUR as per the NICE guidelines Urinary Tract Infection-Child [83]. VCUG is not recommended by NICE guidelines for children >3 years of age with UTI, even if atypical or recurrent UTI [16]. The AAP guidelines suggest VCUG for children 2 to 24 months of age after the second febrile UTI and after the first for patients with abnormalities on renal and bladder US [41].

69444

acrac_69444_16

Urinary Tract Infection Child

MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging. Nuclear Medicine Cystography There is good correlation between nuclear medicine cystography and VCUG for the detection of reflux [19]. For more information, please see the fluoroscopic VCUG section. The literature in this patient population is evolving with a focus on other modalities such as VUS and fluoroscopy VCUG. It should be noted that the primary evidence supporting use of nuclear cystography is generally older than that of other modalities. US Kidneys and Bladder In children with atypical, recurrent, or complicated UTI, the main benefit of US is the detection of underlying abnormalities, calculi, or complications such as a renal or perirenal abscess [82,84]. The potential harm of using US as the only imaging for UTI is the poor sensitivity for VUR and pyelonephritis/scarring [25-30,64]. There are limited data showing inconsistent results on the sensitivity of US in the detection of dilated VUR [65,66]. Grayscale US identifies approximately 25% of the patients with acute pyelonephritis and approximately 40% of the patients with chronic parenchymal scarring [29,31,67-72]. In a retrospective study of 2,259 children <5 years of age, sensitivity was related to criteria for the definition of a normal study.

Urinary Tract Infection Child. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging. MRU Without and With IV Contrast There is no relevant literature to support the use of MRU in the evaluation of a child with atypical or recurrent febrile UTI for initial imaging. Nuclear Medicine Cystography There is good correlation between nuclear medicine cystography and VCUG for the detection of reflux [19]. For more information, please see the fluoroscopic VCUG section. The literature in this patient population is evolving with a focus on other modalities such as VUS and fluoroscopy VCUG. It should be noted that the primary evidence supporting use of nuclear cystography is generally older than that of other modalities. US Kidneys and Bladder In children with atypical, recurrent, or complicated UTI, the main benefit of US is the detection of underlying abnormalities, calculi, or complications such as a renal or perirenal abscess [82,84]. The potential harm of using US as the only imaging for UTI is the poor sensitivity for VUR and pyelonephritis/scarring [25-30,64]. There are limited data showing inconsistent results on the sensitivity of US in the detection of dilated VUR [65,66]. Grayscale US identifies approximately 25% of the patients with acute pyelonephritis and approximately 40% of the patients with chronic parenchymal scarring [29,31,67-72]. In a retrospective study of 2,259 children <5 years of age, sensitivity was related to criteria for the definition of a normal study.

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Urinary Tract Infection Child

With the use of the most relaxed criteria (25% abnormal), US had a sensitivity of 28% (specificity of 77%), and with the most stringent criteria (4% abnormal), US had a sensitivity of 5% (specificity of 97%) [31]. Assuming a 40% prevalence of VUR and a 20% recurrent rate of UTIs in 100 children who have US, up to 11 children will have positive US studies that will be followed by a VCUG study, of which 8 will be positive for VUR. Two years of a prophylactic antibiotic will decrease recurrent UTIs from up to 2 children to 1 child. This means that 1 child will benefit from the US study and an additional 3 children that may benefit from prophylactic antibiotic will not be treated. In addition, with the increased use of prenatal US screening, the yield of detection of unknown renal abnormalities in children with UTIs has decreased [73]. Few studies with small series of children suggest good correlation between power Doppler US and Tc-99m DMSA findings of pyelonephritis [74,75]. Other studies; however, demonstrated a low sensitivity for pyelonephritis and a low prediction for development of renal scarring [49,76,77]. Therefore, the use of power Doppler US as a replacement for nuclear medicine cystography is not useful [26,49,76]. The NICE guidelines for UTI recommend US if the infection is atypical for all ages or recurrent [16]. The AAP guidelines recommend US for children with a febrile UTI from ages 2 to 24 months [41]. Urinary Tract Infection-Child Variant 6: Child. Established vesicoureteral reflux. Follow-up imaging. CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child with established VUR for follow-up imaging. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child with established VUR for follow-up imaging.

Urinary Tract Infection Child. With the use of the most relaxed criteria (25% abnormal), US had a sensitivity of 28% (specificity of 77%), and with the most stringent criteria (4% abnormal), US had a sensitivity of 5% (specificity of 97%) [31]. Assuming a 40% prevalence of VUR and a 20% recurrent rate of UTIs in 100 children who have US, up to 11 children will have positive US studies that will be followed by a VCUG study, of which 8 will be positive for VUR. Two years of a prophylactic antibiotic will decrease recurrent UTIs from up to 2 children to 1 child. This means that 1 child will benefit from the US study and an additional 3 children that may benefit from prophylactic antibiotic will not be treated. In addition, with the increased use of prenatal US screening, the yield of detection of unknown renal abnormalities in children with UTIs has decreased [73]. Few studies with small series of children suggest good correlation between power Doppler US and Tc-99m DMSA findings of pyelonephritis [74,75]. Other studies; however, demonstrated a low sensitivity for pyelonephritis and a low prediction for development of renal scarring [49,76,77]. Therefore, the use of power Doppler US as a replacement for nuclear medicine cystography is not useful [26,49,76]. The NICE guidelines for UTI recommend US if the infection is atypical for all ages or recurrent [16]. The AAP guidelines recommend US for children with a febrile UTI from ages 2 to 24 months [41]. Urinary Tract Infection-Child Variant 6: Child. Established vesicoureteral reflux. Follow-up imaging. CT Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis with IV contrast in the evaluation of a child with established VUR for follow-up imaging. CT Abdomen and Pelvis Without and With IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without and with IV contrast in the evaluation of a child with established VUR for follow-up imaging.

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acrac_69444_18

Urinary Tract Infection Child

CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child with established VUR for follow-up imaging. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child with established VUR for follow-up imaging. DMSA Renal Scan Approximately one-fifth of children may have renal damage after UTI, with significant risk for deterioration [85]. DMSA may be considered for follow-up of children with VUR to detect new renal scarring, especially after a febrile UTI or when renal US is abnormal [61]. Fluoroscopy Voiding Cystourethrography VCUG is recommended by the American Urological Association between 12 and 24 months after UTI with longer intervals between follow-up studies in patients in whom evidence supports lower rates of spontaneous resolution (ie, those with higher grades of VUR [grades III-V], bladder/bowel dysfunction, and older age) [61]. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child with established VUR for follow-up imaging. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child with established VUR for follow-up imaging. MRU Without and With IV Contrast MRU has been suggested as a safer alternative to scintigraphy in children with VUR, particularly those who require follow-up imaging [86,87]. This is pertinent for follow-up imaging of VUR causing renal scarring.

Urinary Tract Infection Child. CT Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of CT abdomen and pelvis without IV contrast in the evaluation of a child with established VUR for follow-up imaging. CTU Without and With IV Contrast There is no relevant literature to support the use of CTU in the evaluation of a child with established VUR for follow-up imaging. DMSA Renal Scan Approximately one-fifth of children may have renal damage after UTI, with significant risk for deterioration [85]. DMSA may be considered for follow-up of children with VUR to detect new renal scarring, especially after a febrile UTI or when renal US is abnormal [61]. Fluoroscopy Voiding Cystourethrography VCUG is recommended by the American Urological Association between 12 and 24 months after UTI with longer intervals between follow-up studies in patients in whom evidence supports lower rates of spontaneous resolution (ie, those with higher grades of VUR [grades III-V], bladder/bowel dysfunction, and older age) [61]. MRI Abdomen and Pelvis With IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis with IV contrast in the evaluation of a child with established VUR for follow-up imaging. MRI Abdomen and Pelvis Without IV Contrast There is no relevant literature to support the use of MRI abdomen and pelvis without IV contrast in the evaluation of a child with established VUR for follow-up imaging. MRU Without and With IV Contrast MRU has been suggested as a safer alternative to scintigraphy in children with VUR, particularly those who require follow-up imaging [86,87]. This is pertinent for follow-up imaging of VUR causing renal scarring.

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acrac_3157911_0

Diffuse Lung Disease

Some of the DLDs, such as idiopathic pulmonary fibrosis, demonstrate episodes of acute exacerbation or acute deterioration as a result of the intrinsic DLD itself. These episodes typically manifest with a 1 to 2 month prodrome of worsening dyspnea or cough and progressive lung disease [11-16]. The development of acute exacerbations is not rare and has significant impact on mortality [17]. Clinically, these episodes frequently overlap with other causes of respiratory illness, such as infection, pulmonary embolism, heart failure, or malignancy. These other causes of acute clinical decline are outside the scope of this work and are best addressed in other ACR Appropriateness Criteria documents. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Diffuse Lung Disease evaluation of DLD distribution [23-26]. In this document, statements regarding the appropriateness of non-contrast CT include the use of such HRCT sequences based on the suspected DLD and clinical questions. FDG-PET/CT Skull Base to Mid-Thigh There is limited research supporting the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT in some DLDs, which does not currently support the use of FDG-PET/CT for initial imaging. FDG-PET/CT may have a secondary role for evaluation of some DLDs because of increased FDG activity that correlates with disease severity and prognosis. A majority of relevant studies focus on sarcoidosis and a minority on fibrotic DLD including idiopathic pulmonary fibrosis [85-105]. MRI Chest There is limited research supporting the use of MRI in DLDs, which does not currently support the use of MRI for initial imaging.

Diffuse Lung Disease. Some of the DLDs, such as idiopathic pulmonary fibrosis, demonstrate episodes of acute exacerbation or acute deterioration as a result of the intrinsic DLD itself. These episodes typically manifest with a 1 to 2 month prodrome of worsening dyspnea or cough and progressive lung disease [11-16]. The development of acute exacerbations is not rare and has significant impact on mortality [17]. Clinically, these episodes frequently overlap with other causes of respiratory illness, such as infection, pulmonary embolism, heart failure, or malignancy. These other causes of acute clinical decline are outside the scope of this work and are best addressed in other ACR Appropriateness Criteria documents. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Diffuse Lung Disease evaluation of DLD distribution [23-26]. In this document, statements regarding the appropriateness of non-contrast CT include the use of such HRCT sequences based on the suspected DLD and clinical questions. FDG-PET/CT Skull Base to Mid-Thigh There is limited research supporting the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT in some DLDs, which does not currently support the use of FDG-PET/CT for initial imaging. FDG-PET/CT may have a secondary role for evaluation of some DLDs because of increased FDG activity that correlates with disease severity and prognosis. A majority of relevant studies focus on sarcoidosis and a minority on fibrotic DLD including idiopathic pulmonary fibrosis [85-105]. MRI Chest There is limited research supporting the use of MRI in DLDs, which does not currently support the use of MRI for initial imaging.

3157911

acrac_3157911_1

Diffuse Lung Disease

Small studies have shown adequate concordance of MRI findings with CT in established cases of DLD utilizing a variety of specialized MRI sequences. Some MRI sequences in the setting of DLD may provide additional functional information such as tissue characterization, gas transfer efficiency, and lung elasticity [106- 118]. Diffuse Lung Disease chest radiograph at time of initial diagnosis of DLD may assist with diagnosis of these other conditions via radiograph on follow-up. FDG-PET/CT Skull Base to Mid-Thigh There is limited research supporting the use of FDG-PET/CT in some DLDs, which does not currently support FDG-PET/CT for imaging of acute exacerbation or acute deterioration of DLD. MRI Chest There is limited research supporting the use of MRI in some DLDs, none of which currently supports the use of MRI for imaging of acute exacerbation or acute deterioration of DLD. FDG-PET/CT Skull Base to Mid-Thigh There is limited research supporting the use of FDG-PET/CT in DLDs. In sarcoidosis, FDG-PET/CT can be used as a marker of disease extent and severity, and it can assist in follow-up and monitoring of treatment response [86,87,89,92,93,95,96,98-100]. Research supporting the use of FDG-PET/CT is more limited in other DLDs but has been evaluated in some studies of lung fibrosis [90,91,102]. Diffuse Lung Disease MRI Chest There is limited research supporting the use of MRI in DLD, none of which currently supports the use of MRI for follow-up imaging. Small studies have shown adequate concordance of MRI findings with CT in established cases of DLD utilizing a variety of specialized MRI sequences. Some MRI sequences in the setting of DLD may provide additional functional information such as tissue characterization, gas transfer efficiency, and lung elasticity. [106- 118]. Radiography Chest There is no research supporting the use of chest radiography over CT for follow-up imaging of confirmed DLD without acute clinical deterioration.

Diffuse Lung Disease. Small studies have shown adequate concordance of MRI findings with CT in established cases of DLD utilizing a variety of specialized MRI sequences. Some MRI sequences in the setting of DLD may provide additional functional information such as tissue characterization, gas transfer efficiency, and lung elasticity [106- 118]. Diffuse Lung Disease chest radiograph at time of initial diagnosis of DLD may assist with diagnosis of these other conditions via radiograph on follow-up. FDG-PET/CT Skull Base to Mid-Thigh There is limited research supporting the use of FDG-PET/CT in some DLDs, which does not currently support FDG-PET/CT for imaging of acute exacerbation or acute deterioration of DLD. MRI Chest There is limited research supporting the use of MRI in some DLDs, none of which currently supports the use of MRI for imaging of acute exacerbation or acute deterioration of DLD. FDG-PET/CT Skull Base to Mid-Thigh There is limited research supporting the use of FDG-PET/CT in DLDs. In sarcoidosis, FDG-PET/CT can be used as a marker of disease extent and severity, and it can assist in follow-up and monitoring of treatment response [86,87,89,92,93,95,96,98-100]. Research supporting the use of FDG-PET/CT is more limited in other DLDs but has been evaluated in some studies of lung fibrosis [90,91,102]. Diffuse Lung Disease MRI Chest There is limited research supporting the use of MRI in DLD, none of which currently supports the use of MRI for follow-up imaging. Small studies have shown adequate concordance of MRI findings with CT in established cases of DLD utilizing a variety of specialized MRI sequences. Some MRI sequences in the setting of DLD may provide additional functional information such as tissue characterization, gas transfer efficiency, and lung elasticity. [106- 118]. Radiography Chest There is no research supporting the use of chest radiography over CT for follow-up imaging of confirmed DLD without acute clinical deterioration.

3157911

acrac_69340_0

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

Introduction/Background The Centers for Disease Control and Prevention National Diabetes Statistics Report of 2017 states that 30.3 million people in the United States have diabetes (9.4% of the population) [1]. Diabetes-related foot complications, such as soft-tissue infection, osteomyelitis, and neuropathic osteoarthropathy, account for up to 20% of all diabetic-related North American hospital admissions, with up to $1.5 billion spent annually in the United States on diabetic foot ulcer care [2]. Neuropathic changes in the foot are present in about 1% of diabetics [3]. Neuropathic osteoarthropathy is a progressive process affecting the bones, joints, and soft tissue of the foot and ankle. Delay in the diagnosis may lead to derangement of the bony architecture of the foot, deformity, recurrent foot ulcerations, cellulitis, osteomyelitis, and amputation [4]. Discussion of Procedures by Variant Variant 1: Suspected osteomyelitis of the foot in patients with diabetes mellitus. Initial imaging. Radiography Foot Radiographs are useful as the initial screening examination. They evaluate anatomic detail and previous surgeries and are useful to evaluate for other causes of pain, such as radiopaque foreign body, soft-tissue gas, fracture, degenerative changes, neuropathic arthropathy, or tumor. Radiographs are insensitive in the detection of early stages of acute osteomyelitis [11]. Soft-tissue swelling and obscuration of the fat planes will precede osseous changes [12]. Osseous changes may take 10 to 12 days to develop in adults [13]. Early bony changes of osseous infection include periosteal reaction, lytic bone destruction, endosteal scalloping, osteopenia, loss of trabecular architecture, and new bone apposition [13]. CT Foot There is no relevant literature to support the use of CT with or without intravenous (IV) contrast as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot.

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. Introduction/Background The Centers for Disease Control and Prevention National Diabetes Statistics Report of 2017 states that 30.3 million people in the United States have diabetes (9.4% of the population) [1]. Diabetes-related foot complications, such as soft-tissue infection, osteomyelitis, and neuropathic osteoarthropathy, account for up to 20% of all diabetic-related North American hospital admissions, with up to $1.5 billion spent annually in the United States on diabetic foot ulcer care [2]. Neuropathic changes in the foot are present in about 1% of diabetics [3]. Neuropathic osteoarthropathy is a progressive process affecting the bones, joints, and soft tissue of the foot and ankle. Delay in the diagnosis may lead to derangement of the bony architecture of the foot, deformity, recurrent foot ulcerations, cellulitis, osteomyelitis, and amputation [4]. Discussion of Procedures by Variant Variant 1: Suspected osteomyelitis of the foot in patients with diabetes mellitus. Initial imaging. Radiography Foot Radiographs are useful as the initial screening examination. They evaluate anatomic detail and previous surgeries and are useful to evaluate for other causes of pain, such as radiopaque foreign body, soft-tissue gas, fracture, degenerative changes, neuropathic arthropathy, or tumor. Radiographs are insensitive in the detection of early stages of acute osteomyelitis [11]. Soft-tissue swelling and obscuration of the fat planes will precede osseous changes [12]. Osseous changes may take 10 to 12 days to develop in adults [13]. Early bony changes of osseous infection include periosteal reaction, lytic bone destruction, endosteal scalloping, osteopenia, loss of trabecular architecture, and new bone apposition [13]. CT Foot There is no relevant literature to support the use of CT with or without intravenous (IV) contrast as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot.

69340

acrac_69340_1

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: [email protected] Suspected Osteomyelitis of the Foot MRI Foot There is no relevant literature to support the use of MRI with or without IV contrast as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. FDG-PET/CT Whole Body There is no relevant literature to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. WBC Scan and Sulfur Colloid Scan Foot There is no relevant literature to support the use of a dual isotope WBC with sulfur colloid scan as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. WBC Scan Foot There is no relevant literature to support the use of In-111 WBC scan as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. 3-phase Bone Scan and WBC Scan and Sulfur Colloid Scan Foot There is no relevant literature to support the use of combined imaging with 3-phase bone scan and In-111 WBC scan and Tc-99m sulfur colloid scan as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. 3-phase Bone Scan and WBC Scan Foot There is no relevant literature to support the use of a 3-phase bone scan with In-111 WBC as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot.

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: [email protected] Suspected Osteomyelitis of the Foot MRI Foot There is no relevant literature to support the use of MRI with or without IV contrast as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. FDG-PET/CT Whole Body There is no relevant literature to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. WBC Scan and Sulfur Colloid Scan Foot There is no relevant literature to support the use of a dual isotope WBC with sulfur colloid scan as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. WBC Scan Foot There is no relevant literature to support the use of In-111 WBC scan as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. 3-phase Bone Scan and WBC Scan and Sulfur Colloid Scan Foot There is no relevant literature to support the use of combined imaging with 3-phase bone scan and In-111 WBC scan and Tc-99m sulfur colloid scan as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. 3-phase Bone Scan and WBC Scan Foot There is no relevant literature to support the use of a 3-phase bone scan with In-111 WBC as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot.

69340

acrac_69340_2

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

3-phase Bone Scan Foot There is no relevant literature to support the use of a 3-phase bone scan as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. US Foot There is no relevant literature to support the use of ultrasound (US) as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. 3-phase Bone Scan and WBC Scan with SPECT or SPECT/CT foot There is no relevant literature to support the use of single-photon emission computed tomography (SPECT/CT) as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. Variant 2: Soft-tissue swelling without ulcer. Suspected osteomyelitis or early neuropathic arthropathy changes of the foot in patients with diabetes mellitus. Additional imaging following radiographs. The likelihood of developing osteomyelitis without an associated wound or ulceration is extremely low. Almost all osteomyelitis and soft-tissue abscesses of the diabetic foot represent areas of contiguous infection from adjacent skin ulcerations and not hematogenous seeding [14]. Any imaging modality performed for this variant should be able to identify soft-tissue infections, tumors and abscesses, early neuropathic arthropathy, or subtle fractures not revealed on initial radiographs. Diabetic foot osteomyelitis and neuroarthropathy can be difficult to differentiate clinically. The early diagnosis of neuropathic disease prior to the development of radiographic change is important, as these patients will be treated with altered footwear and orthotics to prevent the progression to deformity. US Foot US is of limited benefit in the detection of adult osteomyelitis because of its inability to penetrate the cortex of the bone. The role of US in the diabetic foot includes detection of subperiosteal and soft-tissue abscesses, tenosynovitis, joint effusions, and radiolucent foreign bodies.

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. 3-phase Bone Scan Foot There is no relevant literature to support the use of a 3-phase bone scan as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. US Foot There is no relevant literature to support the use of ultrasound (US) as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. 3-phase Bone Scan and WBC Scan with SPECT or SPECT/CT foot There is no relevant literature to support the use of single-photon emission computed tomography (SPECT/CT) as the initial screening examination in diabetic patients with suspected osteomyelitis of the foot. Variant 2: Soft-tissue swelling without ulcer. Suspected osteomyelitis or early neuropathic arthropathy changes of the foot in patients with diabetes mellitus. Additional imaging following radiographs. The likelihood of developing osteomyelitis without an associated wound or ulceration is extremely low. Almost all osteomyelitis and soft-tissue abscesses of the diabetic foot represent areas of contiguous infection from adjacent skin ulcerations and not hematogenous seeding [14]. Any imaging modality performed for this variant should be able to identify soft-tissue infections, tumors and abscesses, early neuropathic arthropathy, or subtle fractures not revealed on initial radiographs. Diabetic foot osteomyelitis and neuroarthropathy can be difficult to differentiate clinically. The early diagnosis of neuropathic disease prior to the development of radiographic change is important, as these patients will be treated with altered footwear and orthotics to prevent the progression to deformity. US Foot US is of limited benefit in the detection of adult osteomyelitis because of its inability to penetrate the cortex of the bone. The role of US in the diabetic foot includes detection of subperiosteal and soft-tissue abscesses, tenosynovitis, joint effusions, and radiolucent foreign bodies.

69340

acrac_69340_3

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

US is insensitive to the marrow edema and trabecular microfractures present in neuropathic foot. CT Foot CT is able to image large anatomic regions rapidly with multiplanar reconstruction capability. CT with or without IV contrast demonstrates the features of acute osteomyelitis, such as periosteal reaction, endosteal scalloping, and lytic bone destruction, more clearly and in more detail than on radiographs but is less sensitive than MRI and nuclear medicine studies for detecting early intramedullary changes of acute osteomyelitis [15]. Features of chronic osteomyelitis (sequestra, involucrum, cloaca, sinus tracts) are well depicted on CT with or without IV contrast. CT with or without IV contrast may be superior to MRI for the findings of sequestra, foreign bodies, and Suspected Osteomyelitis of the Foot soft-tissue gas [16]. CT with or without IV contrast is more sensitive than radiographs to osseous changes allowing earlier detection of neuropathic arthropathy changes of debris, fragmentation, disruption, and dislocation [3,17]. When metal is present in or near the area of interest, there is significant loss of image resolution that is due to a beam-hardening artifact [13]. Dual-energy CT may be useful for metal artifact reduction if available. With high-resolution multiplanar imaging, CT is able to delineate the anatomic extent of soft-tissue infections. Contrast is preferred for the evaluation of soft-tissue infection and delineation of fluid collections [16]. MRI Foot MRI with or without enhancement demonstrates excellent soft-tissue contrast and sensitivity to marrow abnormalities [18,19] with high-resolution detail in multiple anatomic planes. The likelihood of osteomyelitis without an associated wound or ulceration is extremely low.

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. US is insensitive to the marrow edema and trabecular microfractures present in neuropathic foot. CT Foot CT is able to image large anatomic regions rapidly with multiplanar reconstruction capability. CT with or without IV contrast demonstrates the features of acute osteomyelitis, such as periosteal reaction, endosteal scalloping, and lytic bone destruction, more clearly and in more detail than on radiographs but is less sensitive than MRI and nuclear medicine studies for detecting early intramedullary changes of acute osteomyelitis [15]. Features of chronic osteomyelitis (sequestra, involucrum, cloaca, sinus tracts) are well depicted on CT with or without IV contrast. CT with or without IV contrast may be superior to MRI for the findings of sequestra, foreign bodies, and Suspected Osteomyelitis of the Foot soft-tissue gas [16]. CT with or without IV contrast is more sensitive than radiographs to osseous changes allowing earlier detection of neuropathic arthropathy changes of debris, fragmentation, disruption, and dislocation [3,17]. When metal is present in or near the area of interest, there is significant loss of image resolution that is due to a beam-hardening artifact [13]. Dual-energy CT may be useful for metal artifact reduction if available. With high-resolution multiplanar imaging, CT is able to delineate the anatomic extent of soft-tissue infections. Contrast is preferred for the evaluation of soft-tissue infection and delineation of fluid collections [16]. MRI Foot MRI with or without enhancement demonstrates excellent soft-tissue contrast and sensitivity to marrow abnormalities [18,19] with high-resolution detail in multiple anatomic planes. The likelihood of osteomyelitis without an associated wound or ulceration is extremely low.

69340

acrac_69340_4

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

MRI with or without enhancement is a good modality to identify other potential sources of pain in this variant, such as soft-tissue infections, tumors and abscesses, early neuropathic arthropathy, or subtle fractures. Normal marrow signal reliably excludes osteomyelitis [20]. Positive cases of osteomyelitis demonstrate decreased T1-weighted bone marrow signal and increased signal on fluid-sensitive sequences [21,22]. Some authors suggest increased T2-weighted bone marrow signal may represent early osteomyelitis or be a predictor of later development of osteomyelitis, even in the setting of a normal T1-weighted signal [2]. MRI with or without enhancement is often the modality of choice in this variant because of its high sensitivity for osteomyelitis [23-25]. MRI with or without IV contrast can detect the earliest findings of neuropathic arthropathy, such as marrow edema and trabecular microfractures [17,26]. A negative MRI indicates that acute neuropathic arthropathy is unlikely [27]. MRI may be limited by artifact secondary to orthopedic hardware. 3-phase Bone Scan Foot The 3-phase bone scan is sensitive but not specific in differentiating osteomyelitis from a neuropathic foot since both processes cause increased osteoblastic activity [30]. Pathologies with high bone turnover, such as fracture, neuroarthropathy, malignancy, or recent surgery, may result in a positive scan in the absence of infection. A negative bone scan excludes infection with a high degree of certainty [31]. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery.

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. MRI with or without enhancement is a good modality to identify other potential sources of pain in this variant, such as soft-tissue infections, tumors and abscesses, early neuropathic arthropathy, or subtle fractures. Normal marrow signal reliably excludes osteomyelitis [20]. Positive cases of osteomyelitis demonstrate decreased T1-weighted bone marrow signal and increased signal on fluid-sensitive sequences [21,22]. Some authors suggest increased T2-weighted bone marrow signal may represent early osteomyelitis or be a predictor of later development of osteomyelitis, even in the setting of a normal T1-weighted signal [2]. MRI with or without enhancement is often the modality of choice in this variant because of its high sensitivity for osteomyelitis [23-25]. MRI with or without IV contrast can detect the earliest findings of neuropathic arthropathy, such as marrow edema and trabecular microfractures [17,26]. A negative MRI indicates that acute neuropathic arthropathy is unlikely [27]. MRI may be limited by artifact secondary to orthopedic hardware. 3-phase Bone Scan Foot The 3-phase bone scan is sensitive but not specific in differentiating osteomyelitis from a neuropathic foot since both processes cause increased osteoblastic activity [30]. Pathologies with high bone turnover, such as fracture, neuroarthropathy, malignancy, or recent surgery, may result in a positive scan in the absence of infection. A negative bone scan excludes infection with a high degree of certainty [31]. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery.

69340

acrac_69340_5

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

3-phase Bone Scan and WBC Scan Foot The combined bone scan and labeled leukocyte scan (In-111 or Tc-99m) markedly improves specificity in the nonmarrow-containing skeleton when there has been previous surgery, radiographs are abnormal, or when any other cause for bone remodeling is present [32]. It can be useful for distinguishing true WBC accumulation secondary to osteomyelitis from nonspecific WBC uptake that is seen in neuropathic joint [32,33]. Planar scintigraphic imaging modalities alone have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. WBC Scan Foot Labeled leukocyte imaging is advantageous for imaging acute infection in immunocompetent patients with intact chemotaxis. The modality is most useful for identifying neutrophil-mediated inflammatory processes, such as bacterial infections, because the majority of leukocytes labeled are neutrophils, and it is less useful in illnesses in which the predominant cellular response is other than neutrophilic, such as tuberculosis. Chronicity of infection and nonspecific inflammation may lead to inconsistent results, and a recent onset neuropathic joint may yield false-positive results [34,35]. Planar scintigraphic imaging modalities have relatively low spatial resolution and lack of anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. Suspected Osteomyelitis of the Foot WBC Scan and Sulfur Colloid Scan Foot Combined labeled leukocyte and sulfur colloid bone marrow imaging is most useful when increased labeled leukocyte activity is secondary to altered bone marrow distribution, such as around joint prosthesis [36].

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. 3-phase Bone Scan and WBC Scan Foot The combined bone scan and labeled leukocyte scan (In-111 or Tc-99m) markedly improves specificity in the nonmarrow-containing skeleton when there has been previous surgery, radiographs are abnormal, or when any other cause for bone remodeling is present [32]. It can be useful for distinguishing true WBC accumulation secondary to osteomyelitis from nonspecific WBC uptake that is seen in neuropathic joint [32,33]. Planar scintigraphic imaging modalities alone have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. WBC Scan Foot Labeled leukocyte imaging is advantageous for imaging acute infection in immunocompetent patients with intact chemotaxis. The modality is most useful for identifying neutrophil-mediated inflammatory processes, such as bacterial infections, because the majority of leukocytes labeled are neutrophils, and it is less useful in illnesses in which the predominant cellular response is other than neutrophilic, such as tuberculosis. Chronicity of infection and nonspecific inflammation may lead to inconsistent results, and a recent onset neuropathic joint may yield false-positive results [34,35]. Planar scintigraphic imaging modalities have relatively low spatial resolution and lack of anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. Suspected Osteomyelitis of the Foot WBC Scan and Sulfur Colloid Scan Foot Combined labeled leukocyte and sulfur colloid bone marrow imaging is most useful when increased labeled leukocyte activity is secondary to altered bone marrow distribution, such as around joint prosthesis [36].

69340

acrac_69340_6

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

Labeled leukocytes and sulfur colloid normally accumulate in bone marrow, and discordant labeled white cell activity without corresponding sulfur colloid uptake indicates infection [37]. Planar scintigraphy imaging modalities alone have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. 3-phase Bone Scan and WBC Scan and Sulfur Colloid Scan Foot Combined labeled leukocyte and sulfur colloid bone marrow imaging is most useful when increased labeled leukocyte activity is secondary to altered bone marrow distribution, such as around joint prostheses [36]. In evaluating arthroplasties, positive bone scan and WBC uptake with no uptake on the bone marrow scan is considered positive for infection [38]. This modality may be helpful when significant metal hardware is present that would impair MRI or CT imaging. Planar scintigraphic imaging modalities have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. FDG-PET/CT Whole Body FDG-PET/CT has potentially an important role in diagnosing deep soft-tissue infection and osteomyelitis and in differentiating neuropathic arthropathy [39,40]. The high resolution of FDG-PET/CT offers an advantage over single-photon emitting tracers, particularly when evaluating precise localization of radiotracer accumulation in bones of the distal forefoot, where the majority of diabetic foot infections occur [41]. Fused FDG-PET/CT allows correct differentiation between osteomyelitis and soft-tissue infection [42,43].

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. Labeled leukocytes and sulfur colloid normally accumulate in bone marrow, and discordant labeled white cell activity without corresponding sulfur colloid uptake indicates infection [37]. Planar scintigraphy imaging modalities alone have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. 3-phase Bone Scan and WBC Scan and Sulfur Colloid Scan Foot Combined labeled leukocyte and sulfur colloid bone marrow imaging is most useful when increased labeled leukocyte activity is secondary to altered bone marrow distribution, such as around joint prostheses [36]. In evaluating arthroplasties, positive bone scan and WBC uptake with no uptake on the bone marrow scan is considered positive for infection [38]. This modality may be helpful when significant metal hardware is present that would impair MRI or CT imaging. Planar scintigraphic imaging modalities have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. FDG-PET/CT Whole Body FDG-PET/CT has potentially an important role in diagnosing deep soft-tissue infection and osteomyelitis and in differentiating neuropathic arthropathy [39,40]. The high resolution of FDG-PET/CT offers an advantage over single-photon emitting tracers, particularly when evaluating precise localization of radiotracer accumulation in bones of the distal forefoot, where the majority of diabetic foot infections occur [41]. Fused FDG-PET/CT allows correct differentiation between osteomyelitis and soft-tissue infection [42,43].

69340

acrac_69340_7

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

FDG-PET/CT can be used in the evaluation of patients with metal implants that would compromise the accuracy of MRI or CT [40]. Prior studies have demonstrated high accuracy in the detection of osteomyelitis in cases complicated by prior surgery, trauma, and the presence of orthopedic hardware [44-46]. 3-phase Bone Scan and WBC Scan with SPECT or SPECT/CT Foot Planar scintigraphic imaging modalities have relatively low spatial resolution and lack anatomic specificity. SPECT/CT fused imaging improves the diagnostic accuracy mainly because of accurate anatomic localization [47-50]. Dual isotope SPECT/CT is reported to be more accurate than bone scan SPECT/CT or WBC-SPECT/CT alone [51]. Variant 3: Soft-tissue swelling with ulcer. Suspected osteomyelitis of the foot in patients with diabetes mellitus with or without neuropathic arthropathy. Additional imaging following radiographs. Imaging plays a central role in characterizing soft-tissue and osseous infections in the diabetic foot by identifying the location, evaluating the extent of involvement, and detecting complications, such as soft-tissue abscesses or sinus tracts. The infected ulcer may progress to soft-tissue abscess, sinus tract, infected tendon sheath, osteomyelitis, or septic arthritis [29]. If an ulcer with a positive probe-to-bone test is present, the risk of osteomyelitis is 12% to 66% [52-54]. The role of any imaging modality in these patients is to confirm the presence of soft-tissue or osseous infection and determine the anatomic extent for treatment planning. US Foot US demonstrates limited benefit in the detection of adult osteomyelitis because of its inability to penetrate the cortex of the bone. The role of US in the diabetic foot includes detecting subperiosteal and soft-tissue abscesses, tenosynovitis, joint effusions, and radiolucent foreign bodies. US is insensitive to the marrow edema and trabecular microfractures present in neuropathic foot.

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. FDG-PET/CT can be used in the evaluation of patients with metal implants that would compromise the accuracy of MRI or CT [40]. Prior studies have demonstrated high accuracy in the detection of osteomyelitis in cases complicated by prior surgery, trauma, and the presence of orthopedic hardware [44-46]. 3-phase Bone Scan and WBC Scan with SPECT or SPECT/CT Foot Planar scintigraphic imaging modalities have relatively low spatial resolution and lack anatomic specificity. SPECT/CT fused imaging improves the diagnostic accuracy mainly because of accurate anatomic localization [47-50]. Dual isotope SPECT/CT is reported to be more accurate than bone scan SPECT/CT or WBC-SPECT/CT alone [51]. Variant 3: Soft-tissue swelling with ulcer. Suspected osteomyelitis of the foot in patients with diabetes mellitus with or without neuropathic arthropathy. Additional imaging following radiographs. Imaging plays a central role in characterizing soft-tissue and osseous infections in the diabetic foot by identifying the location, evaluating the extent of involvement, and detecting complications, such as soft-tissue abscesses or sinus tracts. The infected ulcer may progress to soft-tissue abscess, sinus tract, infected tendon sheath, osteomyelitis, or septic arthritis [29]. If an ulcer with a positive probe-to-bone test is present, the risk of osteomyelitis is 12% to 66% [52-54]. The role of any imaging modality in these patients is to confirm the presence of soft-tissue or osseous infection and determine the anatomic extent for treatment planning. US Foot US demonstrates limited benefit in the detection of adult osteomyelitis because of its inability to penetrate the cortex of the bone. The role of US in the diabetic foot includes detecting subperiosteal and soft-tissue abscesses, tenosynovitis, joint effusions, and radiolucent foreign bodies. US is insensitive to the marrow edema and trabecular microfractures present in neuropathic foot.

69340

acrac_69340_8

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

CT Foot CT is able to image large anatomic regions rapidly with multiplanar capability. CT with or without IV contrast demonstrates the features of acute osteomyelitis, such as periosteal reaction, endosteal scalloping, and lytic bone destruction, more clearly and in more detail than on radiographs, but is less sensitive than MRI and nuclear medicine studies for detecting early intramedullary changes of acute osteomyelitis [15]. Features of chronic osteomyelitis (sequestra, involucrum, cloaca, sinus tracts) are well depicted on CT with or without IV contrast. CT with or without IV contrast may be superior to MRI for the findings of sequestra, foreign bodies, and soft- tissue gas [16]. CT with or without IV contrast is more sensitive than radiographs to osseous changes, allowing Suspected Osteomyelitis of the Foot earlier detection of neuropathic arthropathy changes of debris, fragmentation, disruption, and dislocation [3,17]. When metal is present in or near the area of interest, there is significant loss of image resolution that is due to a beam-hardening artifact [13]. Dual-energy CT may be useful for metal artifact reduction if available. With high- resolution multiplanar imaging, CT is able to delineate the anatomic extent of soft-tissue infections. Contrast is preferred for the evaluation of soft-tissue infection and delineation of fluid collections [16]. MRI Foot MRI with or without enhancement is the favored modality in this variant and has demonstrated high sensitivity (90%) and specificity (83%) for early osteomyelitis in a large meta-analysis [23]. MRI with or without enhancement demonstrates excellent soft-tissue contrast and sensitivity to marrow abnormalities [18,19] with high-resolution detail in multiple anatomic planes. Normal marrow signal reliably excludes osteomyelitis [20]. Positive cases of osteomyelitis demonstrate decreased T1-weighted bone marrow signal and increased signal on fluid-sensitive sequences [21,22].

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. CT Foot CT is able to image large anatomic regions rapidly with multiplanar capability. CT with or without IV contrast demonstrates the features of acute osteomyelitis, such as periosteal reaction, endosteal scalloping, and lytic bone destruction, more clearly and in more detail than on radiographs, but is less sensitive than MRI and nuclear medicine studies for detecting early intramedullary changes of acute osteomyelitis [15]. Features of chronic osteomyelitis (sequestra, involucrum, cloaca, sinus tracts) are well depicted on CT with or without IV contrast. CT with or without IV contrast may be superior to MRI for the findings of sequestra, foreign bodies, and soft- tissue gas [16]. CT with or without IV contrast is more sensitive than radiographs to osseous changes, allowing Suspected Osteomyelitis of the Foot earlier detection of neuropathic arthropathy changes of debris, fragmentation, disruption, and dislocation [3,17]. When metal is present in or near the area of interest, there is significant loss of image resolution that is due to a beam-hardening artifact [13]. Dual-energy CT may be useful for metal artifact reduction if available. With high- resolution multiplanar imaging, CT is able to delineate the anatomic extent of soft-tissue infections. Contrast is preferred for the evaluation of soft-tissue infection and delineation of fluid collections [16]. MRI Foot MRI with or without enhancement is the favored modality in this variant and has demonstrated high sensitivity (90%) and specificity (83%) for early osteomyelitis in a large meta-analysis [23]. MRI with or without enhancement demonstrates excellent soft-tissue contrast and sensitivity to marrow abnormalities [18,19] with high-resolution detail in multiple anatomic planes. Normal marrow signal reliably excludes osteomyelitis [20]. Positive cases of osteomyelitis demonstrate decreased T1-weighted bone marrow signal and increased signal on fluid-sensitive sequences [21,22].

69340

acrac_69340_9

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

Some authors suggest increased T2-weighted bone marrow signal may represent early osteomyelitis or be a predictor of later development of osteomyelitis, even in the setting of a normal T1-weighted signal [2]. The high resolution can delineate the anatomic extent of osteomyelitis and assist in surgical planning [29]. MRI with or without IV contrast can detect the earliest findings of neuropathic arthropathy, such as marrow edema and trabecular microfractures [17,26]. A negative MRI indicates that acute neuropathic arthropathy is unlikely [27]. MRI may be limited by artifact secondary to orthopedic hardware. 3-phase Bone Scan Foot The 3-phase bone scan is sensitive but not specific in differentiating osteomyelitis from a neuropathic foot since both processes cause increased osteoblastic activity [30]. Pathologies with high bone turnover, such as fracture, neuroarthropathy, malignancy, or recent surgery, may result in a positive scan in the absence of infection. A negative bone scan excludes infection with a high degree of certainty [31]. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. In the setting of deep soft-tissue ulceration, positive uptake in the adjacent bone is highly suggestive of osteomyelitis. 3-phase Bone Scan and WBC Scan Foot The combined bone scan and labeled leukocyte scan (In-111 or Tc-99m) markedly improves specificity in the nonmarrow-containing skeleton when there has been previous surgery, radiographs are abnormal, or when any other cause for bone remodeling is present [32]. It can be useful for distinguishing true WBC accumulation secondary to osteomyelitis from nonspecific WBC uptake that is seen in neuropathic joint [32,33]. Planar scintigraphic imaging modalities alone have relatively low spatial resolution and lack anatomic specificity.

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. Some authors suggest increased T2-weighted bone marrow signal may represent early osteomyelitis or be a predictor of later development of osteomyelitis, even in the setting of a normal T1-weighted signal [2]. The high resolution can delineate the anatomic extent of osteomyelitis and assist in surgical planning [29]. MRI with or without IV contrast can detect the earliest findings of neuropathic arthropathy, such as marrow edema and trabecular microfractures [17,26]. A negative MRI indicates that acute neuropathic arthropathy is unlikely [27]. MRI may be limited by artifact secondary to orthopedic hardware. 3-phase Bone Scan Foot The 3-phase bone scan is sensitive but not specific in differentiating osteomyelitis from a neuropathic foot since both processes cause increased osteoblastic activity [30]. Pathologies with high bone turnover, such as fracture, neuroarthropathy, malignancy, or recent surgery, may result in a positive scan in the absence of infection. A negative bone scan excludes infection with a high degree of certainty [31]. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. In the setting of deep soft-tissue ulceration, positive uptake in the adjacent bone is highly suggestive of osteomyelitis. 3-phase Bone Scan and WBC Scan Foot The combined bone scan and labeled leukocyte scan (In-111 or Tc-99m) markedly improves specificity in the nonmarrow-containing skeleton when there has been previous surgery, radiographs are abnormal, or when any other cause for bone remodeling is present [32]. It can be useful for distinguishing true WBC accumulation secondary to osteomyelitis from nonspecific WBC uptake that is seen in neuropathic joint [32,33]. Planar scintigraphic imaging modalities alone have relatively low spatial resolution and lack anatomic specificity.

69340

acrac_69340_10

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. WBC Scan Foot Labeled leukocyte imaging is advantageous for imaging acute infection in immunocompetent patients with intact chemotaxis. The modality is most useful for identifying neutrophil-mediated inflammatory processes, such as bacterial infections, because the majority of leukocytes labeled are neutrophils, and it is less useful in illnesses in which the predominant cellular response is other than neutrophilic, such as tuberculosis. Chronicity of infection and nonspecific inflammation may lead to inconsistent results, and a recent onset neuropathic joint may yield false-positive results [34,35]. Planar scintigraphic imaging modalities have relatively low spatial resolution and lack of anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. WBC Scan and Sulfur Colloid Scan Foot Combined labeled leukocyte and sulfur colloid bone marrow imaging is most useful when increased labeled leukocyte activity is secondary to altered bone marrow distribution, such as around joint prosthesis [36]. Labeled Suspected Osteomyelitis of the Foot leukocytes and sulfur colloid normally accumulate in bone marrow, and discordant labeled white cell activity without corresponding sulfur colloid uptake indicates infection image [37]. Planar scintigraphic imaging modalities alone have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery.

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. WBC Scan Foot Labeled leukocyte imaging is advantageous for imaging acute infection in immunocompetent patients with intact chemotaxis. The modality is most useful for identifying neutrophil-mediated inflammatory processes, such as bacterial infections, because the majority of leukocytes labeled are neutrophils, and it is less useful in illnesses in which the predominant cellular response is other than neutrophilic, such as tuberculosis. Chronicity of infection and nonspecific inflammation may lead to inconsistent results, and a recent onset neuropathic joint may yield false-positive results [34,35]. Planar scintigraphic imaging modalities have relatively low spatial resolution and lack of anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. WBC Scan and Sulfur Colloid Scan Foot Combined labeled leukocyte and sulfur colloid bone marrow imaging is most useful when increased labeled leukocyte activity is secondary to altered bone marrow distribution, such as around joint prosthesis [36]. Labeled Suspected Osteomyelitis of the Foot leukocytes and sulfur colloid normally accumulate in bone marrow, and discordant labeled white cell activity without corresponding sulfur colloid uptake indicates infection image [37]. Planar scintigraphic imaging modalities alone have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery.

69340

acrac_69340_11

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus

3-phase Bone Scan and WBC Scan and Sulfur Colloid Scan Foot Combined labeled leukocyte and sulfur colloid bone marrow imaging is most useful when increased labeled leukocyte activity is secondary to altered bone marrow distribution, such as around joint prostheses [36]. In evaluating arthroplasties, positive bone scan and WBC uptake with no uptake on the bone marrow scan is considered positive for infection [38]. This modality may be helpful when significant metal hardware is present that would impair MRI or CT imaging. Planar scintigraphic imaging modalities have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. FDG-PET/CT Whole Body FDG-PET/CT has potentially an important role in diagnosing deep soft-tissue infection and osteomyelitis and differentiating neuropathic arthropathy [39,40]. The high resolution of FDG-PET/CT offers an advantage over single-photon emitting tracers, particularly when evaluating precise localization of radiotracer accumulation in bones of the distal forefoot, where the majority of diabetic foot infections occur [41]. Fused FDG-PET/CT allows correct differentiation between osteomyelitis and soft-tissue infection [42,43]. FDG-PET/CT can be used in the evaluation of patients with metal implants that would compromise the accuracy of MRI or CT [40]. Previous studies have demonstrated high accuracy in the detection of osteomyelitis in cases complicated by prior surgery, trauma, and the presence of orthopedic hardware [44-46]. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch. acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation.

Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus. 3-phase Bone Scan and WBC Scan and Sulfur Colloid Scan Foot Combined labeled leukocyte and sulfur colloid bone marrow imaging is most useful when increased labeled leukocyte activity is secondary to altered bone marrow distribution, such as around joint prostheses [36]. In evaluating arthroplasties, positive bone scan and WBC uptake with no uptake on the bone marrow scan is considered positive for infection [38]. This modality may be helpful when significant metal hardware is present that would impair MRI or CT imaging. Planar scintigraphic imaging modalities have relatively low spatial resolution and lack anatomic specificity. Nuclear medicine modalities are useful in cases where infection is multifocal or when the infection is associated with orthopedic hardware or chronic bone alterations from trauma or surgery. FDG-PET/CT Whole Body FDG-PET/CT has potentially an important role in diagnosing deep soft-tissue infection and osteomyelitis and differentiating neuropathic arthropathy [39,40]. The high resolution of FDG-PET/CT offers an advantage over single-photon emitting tracers, particularly when evaluating precise localization of radiotracer accumulation in bones of the distal forefoot, where the majority of diabetic foot infections occur [41]. Fused FDG-PET/CT allows correct differentiation between osteomyelitis and soft-tissue infection [42,43]. FDG-PET/CT can be used in the evaluation of patients with metal implants that would compromise the accuracy of MRI or CT [40]. Previous studies have demonstrated high accuracy in the detection of osteomyelitis in cases complicated by prior surgery, trauma, and the presence of orthopedic hardware [44-46]. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch. acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation.

69340

acrac_69366_0

Adrenal Mass Evaluation

Introduction/Background An adrenal incidentaloma is an unsuspected asymptomatic mass, usually detected on a radiologic study that was obtained for purposes unrelated to adrenal disease [1,2]. The prevalence of incidentally discovered adrenal masses ranges from 4% to 10% on radiological studies, depending on patient age, and from 1% to 8.7% in autopsy specimens [3]. The majority of incidentalomas are benign and most are nonhyperfunctioning adenomas. The prevalence of adenomas in the general population ranges from 1% to 2% [4], although autopsy studies have shown rates as high as 6.6% to 8.7%, depending on the age distribution of the patients. The risk of primary adrenocortical carcinoma in the general population is quite small, on the order of 0.06%; however, among patients with known adrenal masses, the risk is reported to be as high as 4.7% [4]. Other adrenal malignancies, such as angiosarcoma, lymphoma, and pheochromocytoma, are rare in the general population. Many other criteria are involved in the assessment of incidental adrenal masses, including size, growth or stability, and endocrine function. Size is an important variable in predicting malignancy of an incidentally discovered adrenal mass. Smaller lesions are usually benign [11]; therefore, incidental adrenal masses with <1 cm short axis measurement do not generally require further evaluation because of the overwhelming likelihood that these lesions are benign [12]. Conversely, larger lesions have a greater likelihood of being malignant. In addition, interval growth of adrenal masses has also been advocated as a potential indicator of malignancy. If prior imaging is available, and a lesion has been stable for 1 year or more, it can generally be considered benign [12,13]. Even though incidentally discovered adrenal masses are by definition asymptomatic, a proportion will show subclinical function. Current guidelines from the Association of Clinical Endocrinologist and American Association aCleveland Clinic, Cleveland, Ohio.

Adrenal Mass Evaluation. Introduction/Background An adrenal incidentaloma is an unsuspected asymptomatic mass, usually detected on a radiologic study that was obtained for purposes unrelated to adrenal disease [1,2]. The prevalence of incidentally discovered adrenal masses ranges from 4% to 10% on radiological studies, depending on patient age, and from 1% to 8.7% in autopsy specimens [3]. The majority of incidentalomas are benign and most are nonhyperfunctioning adenomas. The prevalence of adenomas in the general population ranges from 1% to 2% [4], although autopsy studies have shown rates as high as 6.6% to 8.7%, depending on the age distribution of the patients. The risk of primary adrenocortical carcinoma in the general population is quite small, on the order of 0.06%; however, among patients with known adrenal masses, the risk is reported to be as high as 4.7% [4]. Other adrenal malignancies, such as angiosarcoma, lymphoma, and pheochromocytoma, are rare in the general population. Many other criteria are involved in the assessment of incidental adrenal masses, including size, growth or stability, and endocrine function. Size is an important variable in predicting malignancy of an incidentally discovered adrenal mass. Smaller lesions are usually benign [11]; therefore, incidental adrenal masses with <1 cm short axis measurement do not generally require further evaluation because of the overwhelming likelihood that these lesions are benign [12]. Conversely, larger lesions have a greater likelihood of being malignant. In addition, interval growth of adrenal masses has also been advocated as a potential indicator of malignancy. If prior imaging is available, and a lesion has been stable for 1 year or more, it can generally be considered benign [12,13]. Even though incidentally discovered adrenal masses are by definition asymptomatic, a proportion will show subclinical function. Current guidelines from the Association of Clinical Endocrinologist and American Association aCleveland Clinic, Cleveland, Ohio.

69366

acrac_69366_1

Adrenal Mass Evaluation

bCleveland Clinic, Cleveland, Ohio. cPanel Chair, Northwestern University, Chicago, Illinois. dPanel Vice-Chair, UT Southwestern Medical Center, Dallas, Texas. eUniversity of Rochester Medical Center, Rochester, New York. fThe University of Texas MD Anderson Cancer Center, Houston, Texas. gUniversity of Washington, Seattle, Washington; American Urological Association. hDuke University Medical Center, Durham, North Carolina. iEmory University School of Medicine, Atlanta, Georgia. jThomas Jefferson University Hospital, Philadelphia, Pennsylvania. kBrigham & Women's Hospital, Boston, Massachusetts. lCleveland Clinic, Cleveland, Ohio. mMedical University of South Carolina, Charleston, South Carolina; American Urological Association. nUniversity of Alabama at Birmingham, Birmingham, Alabama. oUniversity of California San Francisco School of Medicine, San Francisco, California. pJohns Hopkins University School of Medicine, Washington, District of Columbia. qUniversity of Maryland School of Medicine, Baltimore, Maryland. rRhode Island Hospital/The Warren Alpert Medical School of Brown University, Providence, Rhode Island. sSpecialty Chair, University of Alabama at Birmingham, Birmingham, Alabama. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Adrenal Mass Evaluation of Endocrine Surgeons recommend biochemical evaluation of all adrenal incidentalomas to exclude presence of hyperfunctioning lesion [14]. Special Imaging Considerations Adrenal CT A dedicated adrenal CT protocol consists of unenhanced thin-section images through the upper abdomen with axial and coronal reformatted images.

Adrenal Mass Evaluation. bCleveland Clinic, Cleveland, Ohio. cPanel Chair, Northwestern University, Chicago, Illinois. dPanel Vice-Chair, UT Southwestern Medical Center, Dallas, Texas. eUniversity of Rochester Medical Center, Rochester, New York. fThe University of Texas MD Anderson Cancer Center, Houston, Texas. gUniversity of Washington, Seattle, Washington; American Urological Association. hDuke University Medical Center, Durham, North Carolina. iEmory University School of Medicine, Atlanta, Georgia. jThomas Jefferson University Hospital, Philadelphia, Pennsylvania. kBrigham & Women's Hospital, Boston, Massachusetts. lCleveland Clinic, Cleveland, Ohio. mMedical University of South Carolina, Charleston, South Carolina; American Urological Association. nUniversity of Alabama at Birmingham, Birmingham, Alabama. oUniversity of California San Francisco School of Medicine, San Francisco, California. pJohns Hopkins University School of Medicine, Washington, District of Columbia. qUniversity of Maryland School of Medicine, Baltimore, Maryland. rRhode Island Hospital/The Warren Alpert Medical School of Brown University, Providence, Rhode Island. sSpecialty Chair, University of Alabama at Birmingham, Birmingham, Alabama. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Adrenal Mass Evaluation of Endocrine Surgeons recommend biochemical evaluation of all adrenal incidentalomas to exclude presence of hyperfunctioning lesion [14]. Special Imaging Considerations Adrenal CT A dedicated adrenal CT protocol consists of unenhanced thin-section images through the upper abdomen with axial and coronal reformatted images.

69366

acrac_69366_2

Adrenal Mass Evaluation

This allows for initial attenuation measurement of the mass. If diagnostic benign imaging characteristics are not present, a contrast-enhanced series can be performed between 60 and 90 seconds after the administration of intravenous (IV) contrast followed by a 15-minute delayed-phase imaging for evaluation of washout characteristics [15,16]. A study that substituted a 10-minute delayed-phase scan was found to have diminished sensitivity to adenomas compared with a 15-minute delay and is not generally utilized [15]. MRI MR chemical shift imaging (CSI) relies on differences in fat and water molecule precession frequencies and consists of T1-weighted in-phase and opposed-phase dual-echo gradient-recalled echo sequences when both echoes are obtained in the same breath hold. The opposed-phase echo is obtained before the in-phase echo, and lesions with intracytoplasmic fat will be detected by signal intensity loss when opposed-phase images are compared with in- phase images [17]. If MR-CSI is indeterminate, the addition of dynamic postcontrast imaging without or with the addition of T2-weighted imaging has been shown to aid in the diagnosis of adenoma [18-20]. Molecular Imaging PET can be utilized for evaluation of different adrenal abnormalities. Fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET can detect hypermetabolic metastatic lesions. Patients are required to fast for 4 to 6 hours prior to injection of FDG, and data are acquired approximately 60 to 120 minutes after injection. A CT or MRI, respectively, is obtained and a PET scan that covers the same field of view. Co-registered images are then displayed on a workstation for analysis [21]. FDG, 18-F-dihydroxylphenylaalanine (DOPA), Ga-68-DOTATATE, or I-123 metaiodobenzylguanidine (MIBG) can be utilized to identify hyperfunctioning tumors, such as pheochromocytoma.

Adrenal Mass Evaluation. This allows for initial attenuation measurement of the mass. If diagnostic benign imaging characteristics are not present, a contrast-enhanced series can be performed between 60 and 90 seconds after the administration of intravenous (IV) contrast followed by a 15-minute delayed-phase imaging for evaluation of washout characteristics [15,16]. A study that substituted a 10-minute delayed-phase scan was found to have diminished sensitivity to adenomas compared with a 15-minute delay and is not generally utilized [15]. MRI MR chemical shift imaging (CSI) relies on differences in fat and water molecule precession frequencies and consists of T1-weighted in-phase and opposed-phase dual-echo gradient-recalled echo sequences when both echoes are obtained in the same breath hold. The opposed-phase echo is obtained before the in-phase echo, and lesions with intracytoplasmic fat will be detected by signal intensity loss when opposed-phase images are compared with in- phase images [17]. If MR-CSI is indeterminate, the addition of dynamic postcontrast imaging without or with the addition of T2-weighted imaging has been shown to aid in the diagnosis of adenoma [18-20]. Molecular Imaging PET can be utilized for evaluation of different adrenal abnormalities. Fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET can detect hypermetabolic metastatic lesions. Patients are required to fast for 4 to 6 hours prior to injection of FDG, and data are acquired approximately 60 to 120 minutes after injection. A CT or MRI, respectively, is obtained and a PET scan that covers the same field of view. Co-registered images are then displayed on a workstation for analysis [21]. FDG, 18-F-dihydroxylphenylaalanine (DOPA), Ga-68-DOTATATE, or I-123 metaiodobenzylguanidine (MIBG) can be utilized to identify hyperfunctioning tumors, such as pheochromocytoma.

69366

acrac_69366_3

Adrenal Mass Evaluation

FDG-PET/CT is a modality that can further characterize whether a mass is benign versus malignant, as malignant lesions have increased metabolic activity and, therefore, increased glucose avidity compared with benign lesions. Both qualitative and quantitative assessment using standard uptake values (SUVs) is performed to evaluate a lesion. Malignant lesions show increased activity compared with benign lesions with a sensitivity between 93% and 100% [22]. If pheochromocytoma is suspected, then FDG, DOPA, DOTATATE, or MIBG studies can be utilized to improve detection when anatomic localization is inconclusive, to identify additional lesions in the setting of hereditary disease, or to evaluate for metastatic disease [23]. Discussion of Procedures by Variant Variant 1: Indeterminate adrenal mass, less than 1 cm on initial imaging. No diagnostic benign imaging features. No history of malignancy. For patients with no prior history of malignancy and an incidentally detected adrenal mass <1 cm without diagnostic benign imaging characteristics on initial study, the mass is most likely benign [12,24]. One study by Herrera et al [5] examined 342 patients without a history of malignancy and found that the rate of malignancy in adrenal nodules was only 1.5% and that all malignant lesions were >5 cm. Although many guidelines exist regarding the appropriate time interval for follow-up of adrenal nodules, no agreement has been achieved. Stability of a lesion should be assessed by repeat imaging for nodules >1 cm, but there is no literature supporting further evaluation of lesions <1 centimeter. CT Abdomen For lesions <1 cm and no history of malignancy, there is no primary evidence supporting the use of CT for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5]. In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant.

Adrenal Mass Evaluation. FDG-PET/CT is a modality that can further characterize whether a mass is benign versus malignant, as malignant lesions have increased metabolic activity and, therefore, increased glucose avidity compared with benign lesions. Both qualitative and quantitative assessment using standard uptake values (SUVs) is performed to evaluate a lesion. Malignant lesions show increased activity compared with benign lesions with a sensitivity between 93% and 100% [22]. If pheochromocytoma is suspected, then FDG, DOPA, DOTATATE, or MIBG studies can be utilized to improve detection when anatomic localization is inconclusive, to identify additional lesions in the setting of hereditary disease, or to evaluate for metastatic disease [23]. Discussion of Procedures by Variant Variant 1: Indeterminate adrenal mass, less than 1 cm on initial imaging. No diagnostic benign imaging features. No history of malignancy. For patients with no prior history of malignancy and an incidentally detected adrenal mass <1 cm without diagnostic benign imaging characteristics on initial study, the mass is most likely benign [12,24]. One study by Herrera et al [5] examined 342 patients without a history of malignancy and found that the rate of malignancy in adrenal nodules was only 1.5% and that all malignant lesions were >5 cm. Although many guidelines exist regarding the appropriate time interval for follow-up of adrenal nodules, no agreement has been achieved. Stability of a lesion should be assessed by repeat imaging for nodules >1 cm, but there is no literature supporting further evaluation of lesions <1 centimeter. CT Abdomen For lesions <1 cm and no history of malignancy, there is no primary evidence supporting the use of CT for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5]. In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant.

69366

acrac_69366_4

Adrenal Mass Evaluation

The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. FDG-PET/CT Skull Base to Mid-Thigh For lesions <1 cm and no history of malignancy, there is no primary evidence supporting the use of FDG-PET/CT for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5]. In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant. The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. Adrenal Mass Evaluation It is recognized that FDG-PET is less sensitive and specific for lesions <10 mm [25], and although PET has the potential to detect very small adrenal metastases, one study showed that 2 of 5 lesions that proved to be false- negative for malignancy on PET were <10 mm [26]. Therefore, the specificity of FDG-PET for characterizing adrenal lesions <10 mm may be limited. Image-Guided Biopsy Adrenal Gland For lesions <1 cm and no history of malignancy, there is no primary evidence supporting the use of biopsy for initial evaluation [27-30]. MRI Abdomen For lesions <1 cm and no history of malignancy, there is no primary evidence supporting the use of MRI for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5]. In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant. The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. Variant 2: Indeterminate adrenal mass, 1 to 2 cm on initial imaging. No diagnostic benign imaging features. No history of malignancy. Follow-up imaging in 12 months. For patients with no prior history of malignancy and an incidentally detected adrenal mass between 1 and 2 cm without diagnostic benign imaging characteristics on initial study, the mass is most likely benign [12,24].

Adrenal Mass Evaluation. The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. FDG-PET/CT Skull Base to Mid-Thigh For lesions <1 cm and no history of malignancy, there is no primary evidence supporting the use of FDG-PET/CT for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5]. In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant. The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. Adrenal Mass Evaluation It is recognized that FDG-PET is less sensitive and specific for lesions <10 mm [25], and although PET has the potential to detect very small adrenal metastases, one study showed that 2 of 5 lesions that proved to be false- negative for malignancy on PET were <10 mm [26]. Therefore, the specificity of FDG-PET for characterizing adrenal lesions <10 mm may be limited. Image-Guided Biopsy Adrenal Gland For lesions <1 cm and no history of malignancy, there is no primary evidence supporting the use of biopsy for initial evaluation [27-30]. MRI Abdomen For lesions <1 cm and no history of malignancy, there is no primary evidence supporting the use of MRI for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5]. In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant. The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. Variant 2: Indeterminate adrenal mass, 1 to 2 cm on initial imaging. No diagnostic benign imaging features. No history of malignancy. Follow-up imaging in 12 months. For patients with no prior history of malignancy and an incidentally detected adrenal mass between 1 and 2 cm without diagnostic benign imaging characteristics on initial study, the mass is most likely benign [12,24].

69366

acrac_69366_5

Adrenal Mass Evaluation

One study by Herrera et al [5] examined 342 patients without a history of malignancy and found that the rate of malignancy in adrenal nodules was only 1.5% and that all malignant lesions were >5 cm. In another series of 887 patients who had adrenal incidentalomas, a diameter of >4 cm was shown to have 90% sensitivity for the detection of adrenocortical carcinoma but low specificity; only 24% of lesions >4 cm in diameter were malignant [27]. Although many guidelines exist regarding the appropriate time interval for follow-up, no agreement has been achieved. Stability of a lesion >1 cm should be assessed by repeat imaging. If prior imaging is or becomes available or a lesion has been stable for 1 year or more, it can generally be considered benign and no additional imaging follow-up is required; however, imaging may be performed per clinical discretion [13,31]. Therefore, in this clinical scenario, follow-up adrenal-specific imaging can be considered at 12 months to ascertain whether there are benign imaging features and ensure the mass is stable in size. Although both benign and malignant adrenal masses can enlarge over time, interval growth of adrenal masses has been advocated as a potential indicator of malignancy. However, there is scant information on what size change over what time interval requires further investigation. A study has shown that a growth of 0.8 cm on follow-up CT had the highest combination of sensitivity (72%) and specificity (81%) when evaluating absolute size change, growth rate, and growth percent in 111 benign and 25 malignant pathologically proven adrenal lesions. Although the unadjusted odds ratio for this threshold was 11.02, no threshold was found with 100% sensitivity or specificity [32]. Another study of 105 adenomas and 26 malignant nodules found that approximately one-third of adenomas grew, all at a rate of <0.3 cm/year, whereas all malignant nodules grew at a rate of >0.5 cm/year [33].

Adrenal Mass Evaluation. One study by Herrera et al [5] examined 342 patients without a history of malignancy and found that the rate of malignancy in adrenal nodules was only 1.5% and that all malignant lesions were >5 cm. In another series of 887 patients who had adrenal incidentalomas, a diameter of >4 cm was shown to have 90% sensitivity for the detection of adrenocortical carcinoma but low specificity; only 24% of lesions >4 cm in diameter were malignant [27]. Although many guidelines exist regarding the appropriate time interval for follow-up, no agreement has been achieved. Stability of a lesion >1 cm should be assessed by repeat imaging. If prior imaging is or becomes available or a lesion has been stable for 1 year or more, it can generally be considered benign and no additional imaging follow-up is required; however, imaging may be performed per clinical discretion [13,31]. Therefore, in this clinical scenario, follow-up adrenal-specific imaging can be considered at 12 months to ascertain whether there are benign imaging features and ensure the mass is stable in size. Although both benign and malignant adrenal masses can enlarge over time, interval growth of adrenal masses has been advocated as a potential indicator of malignancy. However, there is scant information on what size change over what time interval requires further investigation. A study has shown that a growth of 0.8 cm on follow-up CT had the highest combination of sensitivity (72%) and specificity (81%) when evaluating absolute size change, growth rate, and growth percent in 111 benign and 25 malignant pathologically proven adrenal lesions. Although the unadjusted odds ratio for this threshold was 11.02, no threshold was found with 100% sensitivity or specificity [32]. Another study of 105 adenomas and 26 malignant nodules found that approximately one-third of adenomas grew, all at a rate of <0.3 cm/year, whereas all malignant nodules grew at a rate of >0.5 cm/year [33].

69366

acrac_69366_6

Adrenal Mass Evaluation

CT Abdomen Evaluation of an adrenal mass indeterminate on initial imaging consists of an adrenal CT protocol. Unenhanced thin-section images through the upper abdomen are obtained and then reviewed to evaluate for diagnostic benign imaging features. Some benign lesions, such as cysts and myelolipomas, are readily characterized by CT. Adrenal adenomas contain lipid to varying degrees, and this lowers their attenuation coefficient on unenhanced CT. A threshold value of 10 HU is generally accepted as a cutoff value for diagnosing a lipid-rich adenoma, as the 10 HU threshold has a sensitivity of 71% and specificity of 98% for adenomas [34]. As the threshold value for the HU unit cutoff is increased (for example from 0 to 10 HU), the sensitivity for adenomas increases; however, so does the false-positive rate [35,36]. Lesions that do not contain intracellular lipid (adenoma) or macroscopic fat (myelolipoma) on CT are evaluated with pre- and postcontrast imaging. If there is no enhancement, the lesion may be characterized as a benign lesion such as a cyst or hemorrhage. The use of washout CT may increase the accuracy of characterization compared with MRI. In one small study, washout CT was slightly superior to MR-CSI in characterizing adrenal masses that measured >10 HU on unenhanced CT [42]. Another study demonstrated that washout CT is more accurate than MR-CSI characterization of hyperattenuating adrenal masses, regardless of history of malignancy [43]. Routine abdominal CT without IV contrast will often provide definitive evidence of adenoma. Routine abdominal CT with IV contrast is rarely diagnostic and should not be considered for characterization of a known adrenal lesion. FDG-PET/CT Skull Base to Mid-Thigh For lesions measuring 1 to 2 cm and no history of malignancy, there is no primary evidence supporting the use of FDG-PET/CT for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5].

Adrenal Mass Evaluation. CT Abdomen Evaluation of an adrenal mass indeterminate on initial imaging consists of an adrenal CT protocol. Unenhanced thin-section images through the upper abdomen are obtained and then reviewed to evaluate for diagnostic benign imaging features. Some benign lesions, such as cysts and myelolipomas, are readily characterized by CT. Adrenal adenomas contain lipid to varying degrees, and this lowers their attenuation coefficient on unenhanced CT. A threshold value of 10 HU is generally accepted as a cutoff value for diagnosing a lipid-rich adenoma, as the 10 HU threshold has a sensitivity of 71% and specificity of 98% for adenomas [34]. As the threshold value for the HU unit cutoff is increased (for example from 0 to 10 HU), the sensitivity for adenomas increases; however, so does the false-positive rate [35,36]. Lesions that do not contain intracellular lipid (adenoma) or macroscopic fat (myelolipoma) on CT are evaluated with pre- and postcontrast imaging. If there is no enhancement, the lesion may be characterized as a benign lesion such as a cyst or hemorrhage. The use of washout CT may increase the accuracy of characterization compared with MRI. In one small study, washout CT was slightly superior to MR-CSI in characterizing adrenal masses that measured >10 HU on unenhanced CT [42]. Another study demonstrated that washout CT is more accurate than MR-CSI characterization of hyperattenuating adrenal masses, regardless of history of malignancy [43]. Routine abdominal CT without IV contrast will often provide definitive evidence of adenoma. Routine abdominal CT with IV contrast is rarely diagnostic and should not be considered for characterization of a known adrenal lesion. FDG-PET/CT Skull Base to Mid-Thigh For lesions measuring 1 to 2 cm and no history of malignancy, there is no primary evidence supporting the use of FDG-PET/CT for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5].

69366

acrac_69366_7

Adrenal Mass Evaluation

In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant. The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. Studies have predominantly evaluated FDG-PET or FDG-PET/CT in patients with cancer. However, Tessonnier et al [44] evaluated 41 adrenal tumors in 37 patients who had no history of malignancy using FDG-PET/CT. All tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8 yielded 100% sensitivity and specificity for malignancy. It is recognized that FDG-PET is less sensitive and specific for lesions <10 mm [25], and although PET has the potential to detect very small adrenal metastases, one study showed that 2 of 5 lesions that proved to be false- negative for malignancy on PET were <10 mm [26]. Therefore, the specificity of FDG-PET for characterizing adrenal lesions <10 mm may be limited. Image-Guided Biopsy Adrenal Gland For lesions measuring 1 to 2 cm and no history of malignancy, there is no primary evidence supporting the use of biopsy for initial evaluation [27-30]. Most studies on the efficacy of adrenal biopsy have been performed in a mixed population of patients. Biopsy samples insufficient to make a diagnosis are obtained in 4% to 19% (mean = 15%) of cases [7,45-47]. When sufficient material is obtained, the accuracy of biopsy is between 96% and 100% for malignant lesions. In one study, rates of positive biopsy in three groups with prior diagnosis of cancer, those with previously undiagnosed cancer with simultaneous masses suspicious for metastases, and those with isolated incidentalomas showed positive biopsy results of 70.6%, 69.0%, and 16.7%, respectively. In all three groups, size was a significant predictor of malignancy.

Adrenal Mass Evaluation. In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant. The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. Studies have predominantly evaluated FDG-PET or FDG-PET/CT in patients with cancer. However, Tessonnier et al [44] evaluated 41 adrenal tumors in 37 patients who had no history of malignancy using FDG-PET/CT. All tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8 yielded 100% sensitivity and specificity for malignancy. It is recognized that FDG-PET is less sensitive and specific for lesions <10 mm [25], and although PET has the potential to detect very small adrenal metastases, one study showed that 2 of 5 lesions that proved to be false- negative for malignancy on PET were <10 mm [26]. Therefore, the specificity of FDG-PET for characterizing adrenal lesions <10 mm may be limited. Image-Guided Biopsy Adrenal Gland For lesions measuring 1 to 2 cm and no history of malignancy, there is no primary evidence supporting the use of biopsy for initial evaluation [27-30]. Most studies on the efficacy of adrenal biopsy have been performed in a mixed population of patients. Biopsy samples insufficient to make a diagnosis are obtained in 4% to 19% (mean = 15%) of cases [7,45-47]. When sufficient material is obtained, the accuracy of biopsy is between 96% and 100% for malignant lesions. In one study, rates of positive biopsy in three groups with prior diagnosis of cancer, those with previously undiagnosed cancer with simultaneous masses suspicious for metastases, and those with isolated incidentalomas showed positive biopsy results of 70.6%, 69.0%, and 16.7%, respectively. In all three groups, size was a significant predictor of malignancy.

69366

acrac_69366_8

Adrenal Mass Evaluation

Benign incidentalomas in all three groups had a mean measurement of 2.1 cm, and malignancies had a mean measurement of 9.3 cm [48]. Fine-needle aspiration alone cannot reliably be used to differentiate adrenocortical carcinoma from adrenal adenoma. In addition, the sensitivity of needle biopsy for adrenocortical carcinoma is low. In one study, the sensitivity of needle biopsy for detecting adrenocortical carcinoma was reported as 50% [48]. Another study reports the maximal sensitivity as 70% [49]. In addition, percutaneous biopsy of adrenal lesions is not without risk. Complication rates range from 8% to 12% and consist of bleeding, pneumothorax, infection, and anecdotes of tumor seeding of needle instability should a clinically unsuspected pheochromocytoma be biopsied. Careful correlation with clinical and endocrinological data is needed, combined with knowledge of other features, such as tumor size and imaging characteristics, to distinguish adenoma from carcinoma due to the possibility of sampling error. Thus, biopsy is better suited to a population with a high risk of malignant lesions and is most useful when noninvasive imaging studies are negative or inconclusive. MRI Abdomen Qualitative and quantitative MRI methods have been used to distinguish between adenomas and nonadenomas. An unenhanced MR-CSI (in-phase and opposed-phase gradient-echo scans) relies on differentiating lesions by their Adrenal Mass Evaluation relative lipid content, with malignant lesions having virtually no lipid [50]. This has been shown to be correct for 96% to 100% of cases, depending on the study [51,52]. However, these studies were performed in a mixed population of patients with regard to their history of malignancy, so results may not be directly applicable to populations either with or without known malignancy. Several other authors have shown excellent results in characterizing masses in populations with incidentally detected adrenal masses using simpler CSI techniques [53- 55].

Adrenal Mass Evaluation. Benign incidentalomas in all three groups had a mean measurement of 2.1 cm, and malignancies had a mean measurement of 9.3 cm [48]. Fine-needle aspiration alone cannot reliably be used to differentiate adrenocortical carcinoma from adrenal adenoma. In addition, the sensitivity of needle biopsy for adrenocortical carcinoma is low. In one study, the sensitivity of needle biopsy for detecting adrenocortical carcinoma was reported as 50% [48]. Another study reports the maximal sensitivity as 70% [49]. In addition, percutaneous biopsy of adrenal lesions is not without risk. Complication rates range from 8% to 12% and consist of bleeding, pneumothorax, infection, and anecdotes of tumor seeding of needle instability should a clinically unsuspected pheochromocytoma be biopsied. Careful correlation with clinical and endocrinological data is needed, combined with knowledge of other features, such as tumor size and imaging characteristics, to distinguish adenoma from carcinoma due to the possibility of sampling error. Thus, biopsy is better suited to a population with a high risk of malignant lesions and is most useful when noninvasive imaging studies are negative or inconclusive. MRI Abdomen Qualitative and quantitative MRI methods have been used to distinguish between adenomas and nonadenomas. An unenhanced MR-CSI (in-phase and opposed-phase gradient-echo scans) relies on differentiating lesions by their Adrenal Mass Evaluation relative lipid content, with malignant lesions having virtually no lipid [50]. This has been shown to be correct for 96% to 100% of cases, depending on the study [51,52]. However, these studies were performed in a mixed population of patients with regard to their history of malignancy, so results may not be directly applicable to populations either with or without known malignancy. Several other authors have shown excellent results in characterizing masses in populations with incidentally detected adrenal masses using simpler CSI techniques [53- 55].

69366

acrac_69366_9

Adrenal Mass Evaluation

In cases where the unenhanced CT measurement was between 10 and 30 HU (ie, indeterminate by CT), applying CSI can be discriminatory. In one study, 89% of adenomas with densities between 10 and 30 HU were correctly characterized by CSI [59]. Another study concluded that up to 60% of lesions misclassified by unenhanced CT attenuation measurements can be correctly characterized as adenomas by MR-CSI [53]. Gabriel et al [60] have demonstrated that even heterogeneous loss of signal is evidence of a benign lesion. Thus, MR-CSI may have better sensitivity and specificity than nonenhanced CT. Diffusion-weighted MRI techniques have been investigated in helping to distinguish benign and malignant masses in various organ systems. Neither Miller et al [61] nor Tsushima et al [62] found that this technique could differentiate adrenal adenomas and nonadenomas. A number of series have studied adrenal lesion amount of contrast enhancement and enhancement pattern on MRI after indeterminate MR-CSI [18-20]. In one series of 46 lipid-poor adrenal lesions, the combination of T2-signal intensity and contrast enhancement could identify adenomas with a sensitivity of 84% to 89%, specificity of 96%, and accuracy of 91% to 94% [20]. Additionally, MRI without and with IV contrast may be considered if there is concern for pheochromocytoma, as the contrast can show the typical bright enhancement of this lesion. Contrast can also confirm lack of enhancement of a cystic lesion. Variant 3: Indeterminate adrenal mass, greater than 2 cm and less than 4 cm on initial imaging. No diagnostic benign imaging features. No history of malignancy. Adrenal specific imaging. For patients with no prior history of malignancy and an incidentally detected adrenal mass without diagnostic benign imaging characteristics >2 cm and <4 cm, dedicated adrenal-specific imaging can be considered at the time of detection to determine if the mass can be diagnosed to be an adenoma [16,37,63].

Adrenal Mass Evaluation. In cases where the unenhanced CT measurement was between 10 and 30 HU (ie, indeterminate by CT), applying CSI can be discriminatory. In one study, 89% of adenomas with densities between 10 and 30 HU were correctly characterized by CSI [59]. Another study concluded that up to 60% of lesions misclassified by unenhanced CT attenuation measurements can be correctly characterized as adenomas by MR-CSI [53]. Gabriel et al [60] have demonstrated that even heterogeneous loss of signal is evidence of a benign lesion. Thus, MR-CSI may have better sensitivity and specificity than nonenhanced CT. Diffusion-weighted MRI techniques have been investigated in helping to distinguish benign and malignant masses in various organ systems. Neither Miller et al [61] nor Tsushima et al [62] found that this technique could differentiate adrenal adenomas and nonadenomas. A number of series have studied adrenal lesion amount of contrast enhancement and enhancement pattern on MRI after indeterminate MR-CSI [18-20]. In one series of 46 lipid-poor adrenal lesions, the combination of T2-signal intensity and contrast enhancement could identify adenomas with a sensitivity of 84% to 89%, specificity of 96%, and accuracy of 91% to 94% [20]. Additionally, MRI without and with IV contrast may be considered if there is concern for pheochromocytoma, as the contrast can show the typical bright enhancement of this lesion. Contrast can also confirm lack of enhancement of a cystic lesion. Variant 3: Indeterminate adrenal mass, greater than 2 cm and less than 4 cm on initial imaging. No diagnostic benign imaging features. No history of malignancy. Adrenal specific imaging. For patients with no prior history of malignancy and an incidentally detected adrenal mass without diagnostic benign imaging characteristics >2 cm and <4 cm, dedicated adrenal-specific imaging can be considered at the time of detection to determine if the mass can be diagnosed to be an adenoma [16,37,63].

69366

acrac_69366_10

Adrenal Mass Evaluation

If adrenal-specific imaging is nondiagnostic, a 6- to 12-month follow-up examination can be performed to document stability [12]. One study by Herrera et al [5] examined 342 patients without a history of malignancy and found that the rate of malignancy in adrenal nodules was only 1.5% and that all malignant lesions were >5 cm. In another series of 887 patients who had adrenal incidentalomas, a diameter >4 cm was shown to have 90% sensitivity for the detection of adrenocortical carcinoma but low specificity; only 24% of lesions >4 cm in diameter were malignant [27]. Although many guidelines exist regarding the appropriate time interval for follow-up, no true agreement has been achieved. Stability of a lesion should be assessed by repeat imaging, if possible in the same modality as initial imaging to allow for accurate comparison. If prior imaging is or becomes available or a lesion has been stable for 1 year or more, it can generally be considered benign, and no additional imaging follow-up is required [12,13]; however, it may be performed per clinical discretion. Although both benign and malignant adrenal masses can enlarge over time, interval growth of adrenal masses has been advocated as a potential indicator of malignancy. However, there is scant information on what size change over what time interval requires further investigation. A study has shown that a growth of 0.8 cm on follow-up CT had the highest combination of sensitivity (72%) and specificity (81%) when evaluating absolute size change, growth rate, and growth percent in 111 benign and 25 malignant pathologically proven adrenal lesions. Although the unadjusted odds ratio for this threshold was 11.02, no threshold was found with 100% sensitivity or specificity [32]. Adrenal Mass Evaluation CT Abdomen Evaluation of an adrenal mass indeterminate on initial imaging consists of an adrenal CT protocol.

Adrenal Mass Evaluation. If adrenal-specific imaging is nondiagnostic, a 6- to 12-month follow-up examination can be performed to document stability [12]. One study by Herrera et al [5] examined 342 patients without a history of malignancy and found that the rate of malignancy in adrenal nodules was only 1.5% and that all malignant lesions were >5 cm. In another series of 887 patients who had adrenal incidentalomas, a diameter >4 cm was shown to have 90% sensitivity for the detection of adrenocortical carcinoma but low specificity; only 24% of lesions >4 cm in diameter were malignant [27]. Although many guidelines exist regarding the appropriate time interval for follow-up, no true agreement has been achieved. Stability of a lesion should be assessed by repeat imaging, if possible in the same modality as initial imaging to allow for accurate comparison. If prior imaging is or becomes available or a lesion has been stable for 1 year or more, it can generally be considered benign, and no additional imaging follow-up is required [12,13]; however, it may be performed per clinical discretion. Although both benign and malignant adrenal masses can enlarge over time, interval growth of adrenal masses has been advocated as a potential indicator of malignancy. However, there is scant information on what size change over what time interval requires further investigation. A study has shown that a growth of 0.8 cm on follow-up CT had the highest combination of sensitivity (72%) and specificity (81%) when evaluating absolute size change, growth rate, and growth percent in 111 benign and 25 malignant pathologically proven adrenal lesions. Although the unadjusted odds ratio for this threshold was 11.02, no threshold was found with 100% sensitivity or specificity [32]. Adrenal Mass Evaluation CT Abdomen Evaluation of an adrenal mass indeterminate on initial imaging consists of an adrenal CT protocol.

69366

acrac_69366_11

Adrenal Mass Evaluation

Unenhanced thin-section images through the upper abdomen are obtained and then reviewed to evaluate for diagnostic benign imaging features. Some benign lesions such as cysts and myelolipomas are readily characterized by CT. Adrenal adenomas contain lipid to varying degrees, and this lowers their attenuation coefficient on unenhanced CT. A threshold value of 10 HU is generally accepted as a cutoff value for diagnosing a lipid-rich adenoma, as the 10-HU threshold has a sensitivity of 71% and specificity of 98% for adenomas [34]. As the threshold value for the HU cutoff is increased (for example from 0 HU to 10 HU), the sensitivity for adenomas increases; however, so does the false-positive rate [35,36]. Lesions that do not contain intracellular lipid (adenoma) or macroscopic fat (myelolipoma) on CT are evaluated with pre- and postcontrast imaging. If there is no enhancement, the lesion may be characterized as a benign lesion, such as a cyst or hemorrhage. The use of washout CT may increase accuracy of characterization compared with MRI. In one small study, washout CT was slightly superior to MR-CSI in characterizing adrenal masses that measured >10 HU on unenhanced CT [42]. Another study demonstrated that washout CT is more accurate than MR-CSI characterization of hyperattenuating adrenal masses, regardless of history of malignancy [43]. Routine abdominal CT without IV contrast often will provide definitive evidence of adenoma. Routine abdominal CT with IV contrast is rarely diagnostic and should not be considered for characterization of a known adrenal lesion. FDG-PET/CT Skull Base to Mid-Thigh For lesions >2 cm and <4 cm and no history of malignancy, there is no primary evidence supporting the use of FDG-PET/CT for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5]. In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant.

Adrenal Mass Evaluation. Unenhanced thin-section images through the upper abdomen are obtained and then reviewed to evaluate for diagnostic benign imaging features. Some benign lesions such as cysts and myelolipomas are readily characterized by CT. Adrenal adenomas contain lipid to varying degrees, and this lowers their attenuation coefficient on unenhanced CT. A threshold value of 10 HU is generally accepted as a cutoff value for diagnosing a lipid-rich adenoma, as the 10-HU threshold has a sensitivity of 71% and specificity of 98% for adenomas [34]. As the threshold value for the HU cutoff is increased (for example from 0 HU to 10 HU), the sensitivity for adenomas increases; however, so does the false-positive rate [35,36]. Lesions that do not contain intracellular lipid (adenoma) or macroscopic fat (myelolipoma) on CT are evaluated with pre- and postcontrast imaging. If there is no enhancement, the lesion may be characterized as a benign lesion, such as a cyst or hemorrhage. The use of washout CT may increase accuracy of characterization compared with MRI. In one small study, washout CT was slightly superior to MR-CSI in characterizing adrenal masses that measured >10 HU on unenhanced CT [42]. Another study demonstrated that washout CT is more accurate than MR-CSI characterization of hyperattenuating adrenal masses, regardless of history of malignancy [43]. Routine abdominal CT without IV contrast often will provide definitive evidence of adenoma. Routine abdominal CT with IV contrast is rarely diagnostic and should not be considered for characterization of a known adrenal lesion. FDG-PET/CT Skull Base to Mid-Thigh For lesions >2 cm and <4 cm and no history of malignancy, there is no primary evidence supporting the use of FDG-PET/CT for initial evaluation. Metastatic disease to the adrenal gland without a known history of primary malignancy is unusual [4,5]. In a study of 1,049 incidental adrenal masses in patients with no known history of cancer, none were malignant.

69366

acrac_69366_12

Adrenal Mass Evaluation

The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. Studies have predominantly evaluated FDG-PET or PET/CT in the oncologic population. However, Tessonnier et al [44] used FDG-PET/CT to evaluate 41 adrenal tumors in 37 patients who had no history of malignancy, and all tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8, yielded 100% sensitivity and specificity for malignancy. In addition, it is recognized that FDG-PET is less sensitive and specific for lesions <10 mm [25]. In one study, 2 of 5 lesions that proved to be false-negative for malignancy on PET were <10 mm [26]. 11C-metomidate has been found to localize in adrenocortical tumors and is useful for determining whether a tumor is of adrenocortical origin. However, it cannot distinguish between benign and malignant tumors [64,65]. Image-Guided Biopsy Adrenal Gland For lesions >2 cm and <4 cm and no history of malignancy, there is no primary evidence supporting the use of biopsy for initial evaluation [27-30]. Adrenal Mass Evaluation malignancy. Benign incidentalomas in all three groups had a mean measurement of 2.1 cm, and malignancies had a mean measurement of 9.3 cm [48]. Fine-needle aspiration alone cannot reliably be used to differentiate adrenocortical carcinoma from adrenal adenoma. In addition, the sensitivity of needle biopsy for adrenocortical carcinoma is low. In one study, the sensitivity of needle biopsy for detecting adrenocortical carcinoma was reported as 50% [48]. Another study reports the maximal sensitivity as 70% [49]. In addition, percutaneous biopsy of adrenal lesions is not without risk.

Adrenal Mass Evaluation. The majority of lesions were adrenal adenomas, myelolipomas, and cysts [6]. SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. Studies have predominantly evaluated FDG-PET or PET/CT in the oncologic population. However, Tessonnier et al [44] used FDG-PET/CT to evaluate 41 adrenal tumors in 37 patients who had no history of malignancy, and all tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8, yielded 100% sensitivity and specificity for malignancy. In addition, it is recognized that FDG-PET is less sensitive and specific for lesions <10 mm [25]. In one study, 2 of 5 lesions that proved to be false-negative for malignancy on PET were <10 mm [26]. 11C-metomidate has been found to localize in adrenocortical tumors and is useful for determining whether a tumor is of adrenocortical origin. However, it cannot distinguish between benign and malignant tumors [64,65]. Image-Guided Biopsy Adrenal Gland For lesions >2 cm and <4 cm and no history of malignancy, there is no primary evidence supporting the use of biopsy for initial evaluation [27-30]. Adrenal Mass Evaluation malignancy. Benign incidentalomas in all three groups had a mean measurement of 2.1 cm, and malignancies had a mean measurement of 9.3 cm [48]. Fine-needle aspiration alone cannot reliably be used to differentiate adrenocortical carcinoma from adrenal adenoma. In addition, the sensitivity of needle biopsy for adrenocortical carcinoma is low. In one study, the sensitivity of needle biopsy for detecting adrenocortical carcinoma was reported as 50% [48]. Another study reports the maximal sensitivity as 70% [49]. In addition, percutaneous biopsy of adrenal lesions is not without risk.

69366

acrac_69366_13

Adrenal Mass Evaluation

Complication rates range from 8% to 12% and consist of bleeding, pneumothorax, infection, and anecdotes of tumor seeding of needle instability should a clinically unsuspected pheochromocytoma be biopsied. Careful correlation with clinical and endocrinological data is needed, combined with knowledge of other features, such as tumor size and imaging characteristics to distinguish adenoma from carcinoma due to the possibility of sampling error. Thus, biopsy is better suited to a population with a high risk of malignant lesions and is most useful when noninvasive imaging studies are negative or inconclusive. MRI Abdomen Qualitative and quantitative MRI methods have been used to attempt to distinguish between adenomas and nonadenomas. MR-CSI (in-phase and opposed-phase gradient-echo scans) relies on differentiating lesions by their relative lipid content, with malignant lesions having virtually no lipid [50]. This has been shown to be correct for 96% to 100% of the cases, depending on the study [51,52]. However, these studies were performed in a mixed population of patients with regard to their history of malignancy, so results may not be directly applicable to populations either with or without known malignancy. Several other authors have shown excellent results in characterizing masses in populations with incidentally detected adrenal masses using simpler CSI techniques [53- 55]. In cases in which the unenhanced CT attenuation measurement was between 10 and 30 HU (ie, indeterminate by CT), applying CSI can be discriminatory. In one study, 89% of adenomas with densities between 10 and 30 HU were correctly characterized by CSI [59]. Another study concluded that up to 60% of lesions misclassified by unenhanced CT attenuation measurements can be correctly characterized as adenomas by MR-CSI [53]. Gabriel et al [60] have demonstrated that even heterogeneous loss of signal is evidence of a benign lesion. Thus, MR-CSI may have better sensitivity and specificity than nonenhanced CT.

Adrenal Mass Evaluation. Complication rates range from 8% to 12% and consist of bleeding, pneumothorax, infection, and anecdotes of tumor seeding of needle instability should a clinically unsuspected pheochromocytoma be biopsied. Careful correlation with clinical and endocrinological data is needed, combined with knowledge of other features, such as tumor size and imaging characteristics to distinguish adenoma from carcinoma due to the possibility of sampling error. Thus, biopsy is better suited to a population with a high risk of malignant lesions and is most useful when noninvasive imaging studies are negative or inconclusive. MRI Abdomen Qualitative and quantitative MRI methods have been used to attempt to distinguish between adenomas and nonadenomas. MR-CSI (in-phase and opposed-phase gradient-echo scans) relies on differentiating lesions by their relative lipid content, with malignant lesions having virtually no lipid [50]. This has been shown to be correct for 96% to 100% of the cases, depending on the study [51,52]. However, these studies were performed in a mixed population of patients with regard to their history of malignancy, so results may not be directly applicable to populations either with or without known malignancy. Several other authors have shown excellent results in characterizing masses in populations with incidentally detected adrenal masses using simpler CSI techniques [53- 55]. In cases in which the unenhanced CT attenuation measurement was between 10 and 30 HU (ie, indeterminate by CT), applying CSI can be discriminatory. In one study, 89% of adenomas with densities between 10 and 30 HU were correctly characterized by CSI [59]. Another study concluded that up to 60% of lesions misclassified by unenhanced CT attenuation measurements can be correctly characterized as adenomas by MR-CSI [53]. Gabriel et al [60] have demonstrated that even heterogeneous loss of signal is evidence of a benign lesion. Thus, MR-CSI may have better sensitivity and specificity than nonenhanced CT.

69366

acrac_69366_14

Adrenal Mass Evaluation

Whether diffusion-weighted MRI techniques are helpful in distinguishing benign and malignant masses in various organ systems has been investigated. Neither Miller et al [61] nor Tsushima et al [62] found that this technique could differentiate adrenal adenomas and nonadenomas. For the diagnosis of adenoma, contrast-enhanced MRI does not provide additional information beyond the unenhanced technique. However, MRI without and with IV contrast may be considered if there is concern for pheochromocytoma, as the contrast can show the typical bright enhancement of this lesion. Contrast can also confirm lack of enhancement of a cystic lesion. Adrenocortical carcinomas can be functioning or nonfunctioning. Those with nonfunctioning tumors most often present with a large mass and symptoms such as abdominal or flank pain. Because of the typically late presentation of nonfunctioning tumors, metastatic disease is common. For those smaller masses discovered incidentally and as functioning tumors, which most likely present with Cushing syndrome or virialization, metastatic disease at the time of presentation is less likely [66]. Adrenal Mass Evaluation One study by Herrera et al [5] examined 342 patients without a history of malignancy and found that although the rate of malignancy in all adrenal nodules was only 1.5%, all malignant lesions were >5 cm. In a series of 887 patients who had adrenal incidentalomas, a diameter >4 cm was shown to have 90% sensitivity for the detection of adrenocortical carcinoma but low specificity, as only 24% of lesions >4 cm in diameter were malignant [27]. In contrast, in patients with a history of malignancy, Candel et al [11] found that 87% of lesions <3 cm were benign and that >95% of lesions >3 cm were malignant. In a similar population, Lee et al [35] found that 79% of lesions <2.5 cm were benign. Van Erkel et al [67] in a mixed population showed that a threshold of 3.1 cm discriminated 93% of lesions.

Adrenal Mass Evaluation. Whether diffusion-weighted MRI techniques are helpful in distinguishing benign and malignant masses in various organ systems has been investigated. Neither Miller et al [61] nor Tsushima et al [62] found that this technique could differentiate adrenal adenomas and nonadenomas. For the diagnosis of adenoma, contrast-enhanced MRI does not provide additional information beyond the unenhanced technique. However, MRI without and with IV contrast may be considered if there is concern for pheochromocytoma, as the contrast can show the typical bright enhancement of this lesion. Contrast can also confirm lack of enhancement of a cystic lesion. Adrenocortical carcinomas can be functioning or nonfunctioning. Those with nonfunctioning tumors most often present with a large mass and symptoms such as abdominal or flank pain. Because of the typically late presentation of nonfunctioning tumors, metastatic disease is common. For those smaller masses discovered incidentally and as functioning tumors, which most likely present with Cushing syndrome or virialization, metastatic disease at the time of presentation is less likely [66]. Adrenal Mass Evaluation One study by Herrera et al [5] examined 342 patients without a history of malignancy and found that although the rate of malignancy in all adrenal nodules was only 1.5%, all malignant lesions were >5 cm. In a series of 887 patients who had adrenal incidentalomas, a diameter >4 cm was shown to have 90% sensitivity for the detection of adrenocortical carcinoma but low specificity, as only 24% of lesions >4 cm in diameter were malignant [27]. In contrast, in patients with a history of malignancy, Candel et al [11] found that 87% of lesions <3 cm were benign and that >95% of lesions >3 cm were malignant. In a similar population, Lee et al [35] found that 79% of lesions <2.5 cm were benign. Van Erkel et al [67] in a mixed population showed that a threshold of 3.1 cm discriminated 93% of lesions.

69366

acrac_69366_15

Adrenal Mass Evaluation

Studies have predominantly evaluated FDG-PET or FDG-PET/CT in the oncologic population. SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. However, Tessonnier et al [44] evaluated 41 adrenal tumors in 37 patients who had no history of malignancy using FDG-PET/CT. All tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8 yielded 100% sensitivity and specificity for malignancy. 11C-metomidate has been found to localize in adrenocortical tumors and is useful for determining whether a tumor is of adrenocortical origin. However, it cannot distinguish between benign and malignant tumors [64,65]. Fine-needle aspiration alone cannot reliably be used to differentiate adrenocortical carcinoma from adrenal adenoma. In addition, the sensitivity of needle biopsy for adrenocortical carcinoma is low. In one study, the sensitivity of needle biopsy for detecting adrenocortical carcinoma was reported as 50% [48]. Another study reports the maximal sensitivity as 70% [49]. In addition, percutaneous biopsy of adrenal lesions is not without risk. Complication rates range from 8% to 12% and consist of bleeding, pneumothorax, infection, and anecdotes of tumor seeding of needle tracts. Careful correlation with clinical and endocrinological data is needed, combined with knowledge of other features, such as tumor size and imaging characteristics, to distinguish adenoma from carcinoma due to the possibility of sampling error. Thus, biopsy is better suited to a population with a high risk of malignant lesions and is most useful when noninvasive imaging studies are negative or inconclusive. Adrenal Mass Evaluation Variant 5: Adrenal mass, less than 4 cm on initial imaging. No diagnostic benign imaging features. History of malignancy. Adrenal specific imaging.

Adrenal Mass Evaluation. Studies have predominantly evaluated FDG-PET or FDG-PET/CT in the oncologic population. SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. However, Tessonnier et al [44] evaluated 41 adrenal tumors in 37 patients who had no history of malignancy using FDG-PET/CT. All tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8 yielded 100% sensitivity and specificity for malignancy. 11C-metomidate has been found to localize in adrenocortical tumors and is useful for determining whether a tumor is of adrenocortical origin. However, it cannot distinguish between benign and malignant tumors [64,65]. Fine-needle aspiration alone cannot reliably be used to differentiate adrenocortical carcinoma from adrenal adenoma. In addition, the sensitivity of needle biopsy for adrenocortical carcinoma is low. In one study, the sensitivity of needle biopsy for detecting adrenocortical carcinoma was reported as 50% [48]. Another study reports the maximal sensitivity as 70% [49]. In addition, percutaneous biopsy of adrenal lesions is not without risk. Complication rates range from 8% to 12% and consist of bleeding, pneumothorax, infection, and anecdotes of tumor seeding of needle tracts. Careful correlation with clinical and endocrinological data is needed, combined with knowledge of other features, such as tumor size and imaging characteristics, to distinguish adenoma from carcinoma due to the possibility of sampling error. Thus, biopsy is better suited to a population with a high risk of malignant lesions and is most useful when noninvasive imaging studies are negative or inconclusive. Adrenal Mass Evaluation Variant 5: Adrenal mass, less than 4 cm on initial imaging. No diagnostic benign imaging features. History of malignancy. Adrenal specific imaging.

69366

acrac_69366_16

Adrenal Mass Evaluation

For patients with a history of malignancy and an adrenal mass >1 cm and <4 cm and no diagnostic benign imaging features on prior examinations or documented stability, adrenal-specific imaging should be performed. If adrenal- specific imaging does not characterize the lesion as benign or if the results are indeterminate, evaluation of other imaging features, such as presence of central necrosis and presence of irregular margins or thick enhancing rim, can indicate an increased likelihood of malignancy [74]. In these instances, adrenal biopsy or FDG-PET/CT should be considered for further evaluation [75]. In patients with a history of malignancy, Candel et al [11] found that 87% of lesions <3 cm were benign and that >95% of lesions >3 cm were malignant. In a similar population, Lee et al [35] found that 79% of lesions <2.5 cm were benign. Van Erkel et al [67] in a mixed population showed that a threshold of 3.1 cm discriminated 93% of lesions. CT Abdomen Evaluation of an adrenal mass indeterminate on initial imaging consists of an adrenal CT protocol. Unenhanced thin-section images through the upper abdomen are obtained and then reviewed to evaluate for diagnostic benign imaging features. Some benign lesions, such as cysts and myelolipomas, are readily characterized by CT. Adrenal adenomas contain lipid to varying degrees, and this lowers their attenuation coefficient on unenhanced CT. A threshold value of 10 HU is generally accepted as a cutoff value for diagnosing a lipid-rich adenoma, as the 10 HU threshold has a sensitivity of 71% and specificity of 98% for adenomas [34]. As the threshold value for HU unit cutoff is increased (for example from 0 to 10 HU), the sensitivity for adenomas increases; however, so does the false-positive rate [35,36]. Lesions that do not contain intracellular lipid (adenoma) or macroscopic fat (myelolipoma) on CT are evaluated with pre- and postcontrast imaging.

Adrenal Mass Evaluation. For patients with a history of malignancy and an adrenal mass >1 cm and <4 cm and no diagnostic benign imaging features on prior examinations or documented stability, adrenal-specific imaging should be performed. If adrenal- specific imaging does not characterize the lesion as benign or if the results are indeterminate, evaluation of other imaging features, such as presence of central necrosis and presence of irregular margins or thick enhancing rim, can indicate an increased likelihood of malignancy [74]. In these instances, adrenal biopsy or FDG-PET/CT should be considered for further evaluation [75]. In patients with a history of malignancy, Candel et al [11] found that 87% of lesions <3 cm were benign and that >95% of lesions >3 cm were malignant. In a similar population, Lee et al [35] found that 79% of lesions <2.5 cm were benign. Van Erkel et al [67] in a mixed population showed that a threshold of 3.1 cm discriminated 93% of lesions. CT Abdomen Evaluation of an adrenal mass indeterminate on initial imaging consists of an adrenal CT protocol. Unenhanced thin-section images through the upper abdomen are obtained and then reviewed to evaluate for diagnostic benign imaging features. Some benign lesions, such as cysts and myelolipomas, are readily characterized by CT. Adrenal adenomas contain lipid to varying degrees, and this lowers their attenuation coefficient on unenhanced CT. A threshold value of 10 HU is generally accepted as a cutoff value for diagnosing a lipid-rich adenoma, as the 10 HU threshold has a sensitivity of 71% and specificity of 98% for adenomas [34]. As the threshold value for HU unit cutoff is increased (for example from 0 to 10 HU), the sensitivity for adenomas increases; however, so does the false-positive rate [35,36]. Lesions that do not contain intracellular lipid (adenoma) or macroscopic fat (myelolipoma) on CT are evaluated with pre- and postcontrast imaging.

69366

acrac_69366_17

Adrenal Mass Evaluation

If there is no enhancement, the lesion may be characterized as a benign lesion, such as a cyst or hemorrhage. Metastases from particular primary malignancies, namely hepatocellular carcinoma or clear-cell renal cell carcinoma, have been shown to mimic adenoma based on their washout values. In one study, 84% (16 of 19) of metastases from these two primary tumors would be falsely considered lipid-poor adenomas if washout characteristics alone were used [76]. The use of washout CT may increase accuracy of characterization compared with MRI. In one small study, washout CT was slightly superior to MR-CSI in characterizing adrenal masses measuring >10 HU on unenhanced CT [42]. Another study demonstrated that washout CT is more accurate than MR-CSI characterization of hyperattenuating adrenal masses, regardless of history of malignancy [43]. Routine abdominal CT without IV contrast often will provide definitive evidence of adenoma. Routine abdominal CT with IV contrast is rarely diagnostic and should not be considered for characterization of a known adrenal lesion. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET can be used to identify metastases in oncologic patients in various cancers [26,77-79]. FDG-PET is sensitive to metabolically active lesions, and metastases usually show greater uptake than benign lesions. In several studies, there have been a few false-positives with FDG-PET, lowering specificity to 85% in one study [80], but excellent sensitivity has been achieved [26,77-79]. False-negative scans have occurred in renal cell carcinoma metastases [64]. Adrenal Mass Evaluation SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. Studies have predominantly evaluated FDG-PET or FDG-PET/CT in the oncologic population. However, Tessonnier et al [44] evaluated 41 adrenal tumors in 37 patients who had no history of malignancy using FDG-PET/CT.

Adrenal Mass Evaluation. If there is no enhancement, the lesion may be characterized as a benign lesion, such as a cyst or hemorrhage. Metastases from particular primary malignancies, namely hepatocellular carcinoma or clear-cell renal cell carcinoma, have been shown to mimic adenoma based on their washout values. In one study, 84% (16 of 19) of metastases from these two primary tumors would be falsely considered lipid-poor adenomas if washout characteristics alone were used [76]. The use of washout CT may increase accuracy of characterization compared with MRI. In one small study, washout CT was slightly superior to MR-CSI in characterizing adrenal masses measuring >10 HU on unenhanced CT [42]. Another study demonstrated that washout CT is more accurate than MR-CSI characterization of hyperattenuating adrenal masses, regardless of history of malignancy [43]. Routine abdominal CT without IV contrast often will provide definitive evidence of adenoma. Routine abdominal CT with IV contrast is rarely diagnostic and should not be considered for characterization of a known adrenal lesion. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET can be used to identify metastases in oncologic patients in various cancers [26,77-79]. FDG-PET is sensitive to metabolically active lesions, and metastases usually show greater uptake than benign lesions. In several studies, there have been a few false-positives with FDG-PET, lowering specificity to 85% in one study [80], but excellent sensitivity has been achieved [26,77-79]. False-negative scans have occurred in renal cell carcinoma metastases [64]. Adrenal Mass Evaluation SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. Studies have predominantly evaluated FDG-PET or FDG-PET/CT in the oncologic population. However, Tessonnier et al [44] evaluated 41 adrenal tumors in 37 patients who had no history of malignancy using FDG-PET/CT.

69366

acrac_69366_18

Adrenal Mass Evaluation

All tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8 yielded 100% sensitivity and specificity for malignancy. 11C-metomidate has been found to localize in adrenocortical tumors and is useful for determining whether a tumor is of adrenocortical origin. However, it cannot distinguish between benign and malignant tumors [64,65]. PET/CT sensitivity to small lesions is diminished and may not detect lesions <1 cm. Image-Guided Biopsy Adrenal Gland In the setting of known primary malignancy, adrenal mass biopsy can be performed when noninvasive tests are inconclusive, when enlarging adrenal masses are seen at follow-up imaging, or to confirm the presence of an adrenal metastasis [81]. If other metastases are present, biopsy may not be necessary. Fine-needle aspiration alone cannot reliably be used to differentiate adrenocortical carcinoma from adrenal adenoma. Also, the sensitivity of needle biopsy for adrenocortical carcinoma is low. In one study, the sensitivity of needle biopsy for detecting adrenocortical carcinoma was reported as 50% [48]. Another study reported the sensitivity as 70% maximally [49]. In addition, percutaneous biopsy of adrenal lesions is not without risk. Complication rates range from 8% to 12% and consist of bleeding, pneumothorax, infection, and anecdotes of tumor seeding of needle tracts. Careful correlation with clinical and endocrinological data is needed, combined with knowledge of other features, such as tumor size and imaging characteristics, to distinguish adenoma from carcinoma due to the possibility of sampling error. Thus, biopsy is better suited to a population with a high risk of malignant lesions and is most useful when noninvasive imaging studies are negative or inconclusive. MRI Abdomen Qualitative and quantitative MRI methods have been used to attempt to distinguish between adenomas and nonadenomas.

Adrenal Mass Evaluation. All tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8 yielded 100% sensitivity and specificity for malignancy. 11C-metomidate has been found to localize in adrenocortical tumors and is useful for determining whether a tumor is of adrenocortical origin. However, it cannot distinguish between benign and malignant tumors [64,65]. PET/CT sensitivity to small lesions is diminished and may not detect lesions <1 cm. Image-Guided Biopsy Adrenal Gland In the setting of known primary malignancy, adrenal mass biopsy can be performed when noninvasive tests are inconclusive, when enlarging adrenal masses are seen at follow-up imaging, or to confirm the presence of an adrenal metastasis [81]. If other metastases are present, biopsy may not be necessary. Fine-needle aspiration alone cannot reliably be used to differentiate adrenocortical carcinoma from adrenal adenoma. Also, the sensitivity of needle biopsy for adrenocortical carcinoma is low. In one study, the sensitivity of needle biopsy for detecting adrenocortical carcinoma was reported as 50% [48]. Another study reported the sensitivity as 70% maximally [49]. In addition, percutaneous biopsy of adrenal lesions is not without risk. Complication rates range from 8% to 12% and consist of bleeding, pneumothorax, infection, and anecdotes of tumor seeding of needle tracts. Careful correlation with clinical and endocrinological data is needed, combined with knowledge of other features, such as tumor size and imaging characteristics, to distinguish adenoma from carcinoma due to the possibility of sampling error. Thus, biopsy is better suited to a population with a high risk of malignant lesions and is most useful when noninvasive imaging studies are negative or inconclusive. MRI Abdomen Qualitative and quantitative MRI methods have been used to attempt to distinguish between adenomas and nonadenomas.

69366

acrac_69366_19

Adrenal Mass Evaluation

MR-CSI (in-phase and opposed-phase gradient-echo scans), which relies on differentiating lesions whether lesions have fat within tumor cells, with malignant lesions having virtually no fat [50]. This has been shown to be correct for 96% to 100% of cases, depending on the study [51,52]. However, these studies were performed in a mixed population of patients with regard to their history of malignancy, so results may not be directly applicable to populations either with or without known malignancy. As in CT washout characterization, there can be false-positives for adenoma when interpreting CSI with particular metastatic lesions, specifically from clear-cell renal cell carcinoma and hepatocellular carcinoma. Because the diagnosis of adenoma relies on the detection of fat within tumor cells and because hepatocellular carcinoma and renal cell carcinoma primary tumors contain fat in their cells, both hepatocellular carcinoma and renal cell carcinoma adrenal metastases can contain fat and, thus, mimic adenomas [58,82,83]. In cases in which the unenhanced CT attenuation measurement was between 10 and 30 HU (ie, indeterminate by CT), applying CSI can be discriminatory. In one study, 89% of adenomas with densities between 10 and 30 HU were correctly characterized by CSI [59]. Another study concluded that up to 60% of lesions misclassified by Adrenal Mass Evaluation unenhanced CT attenuation measurements can be correctly characterized as adenomas by MR-CSI [53]. Gabriel et al [60] have demonstrated that even heterogeneous loss of signal is evidence of a benign lesion. Thus, MR-CSI may have better sensitivity and specificity than nonenhanced CT. Diffusion-weighted MRI techniques have been investigated in helping to distinguish benign and malignant masses in various organ systems. Neither Miller et al [61] nor Tsushima et al [62] found that this technique could differentiate adrenal adenomas and nonadenomas.

Adrenal Mass Evaluation. MR-CSI (in-phase and opposed-phase gradient-echo scans), which relies on differentiating lesions whether lesions have fat within tumor cells, with malignant lesions having virtually no fat [50]. This has been shown to be correct for 96% to 100% of cases, depending on the study [51,52]. However, these studies were performed in a mixed population of patients with regard to their history of malignancy, so results may not be directly applicable to populations either with or without known malignancy. As in CT washout characterization, there can be false-positives for adenoma when interpreting CSI with particular metastatic lesions, specifically from clear-cell renal cell carcinoma and hepatocellular carcinoma. Because the diagnosis of adenoma relies on the detection of fat within tumor cells and because hepatocellular carcinoma and renal cell carcinoma primary tumors contain fat in their cells, both hepatocellular carcinoma and renal cell carcinoma adrenal metastases can contain fat and, thus, mimic adenomas [58,82,83]. In cases in which the unenhanced CT attenuation measurement was between 10 and 30 HU (ie, indeterminate by CT), applying CSI can be discriminatory. In one study, 89% of adenomas with densities between 10 and 30 HU were correctly characterized by CSI [59]. Another study concluded that up to 60% of lesions misclassified by Adrenal Mass Evaluation unenhanced CT attenuation measurements can be correctly characterized as adenomas by MR-CSI [53]. Gabriel et al [60] have demonstrated that even heterogeneous loss of signal is evidence of a benign lesion. Thus, MR-CSI may have better sensitivity and specificity than nonenhanced CT. Diffusion-weighted MRI techniques have been investigated in helping to distinguish benign and malignant masses in various organ systems. Neither Miller et al [61] nor Tsushima et al [62] found that this technique could differentiate adrenal adenomas and nonadenomas.

69366

acrac_69366_20

Adrenal Mass Evaluation

For the diagnosis of adenoma versus metastasis, contrast- enhanced MRI does not provide additional information beyond the unenhanced technique. However, MRI without and with IV contrast may be considered if there is concern for pheochromocytoma or hypervascular metastasis, as the contrast can show the typical bright enhancement of this lesion. Contrast can also confirm lack of enhancement of a cystic lesion. In patients with a history of malignancy, Candel et al [11] found that 87% of lesions <3 cm were benign and that >95% of lesions >3 cm were malignant. In a similar population, Lee et al [35] found that 79% of lesions <2.5 cm were benign. Van Erkel et al [67] in a mixed population showed that a threshold of 3.1 cm discriminated 93% of lesions. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET can be used to identify metastases in oncologic patients in various cancers [26,77-79]. FDG-PET is sensitive to metabolically active lesions, and metastases usually show greater uptake than benign lesions. In several studies, there have been a few false-positives with FDG-PET, lowering specificity to 85% in one study [80], but excellent sensitivity has been achieved [26,77-79]. False-negative scans have occurred in renal cell carcinoma metastases [64]. SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. Studies have predominantly evaluated FDG-PET or FDG-PET/CT in the oncologic population. However, Tessonnier et al [44] evaluated 41 adrenal tumors in 37 patients who had no history of malignancy using FDG-PET/CT. All tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8 yielded 100% sensitivity and specificity for malignancy. 11C-metomidate has been found to localize in adrenocortical tumors and is useful for determining whether a tumor is of adrenocortical origin.

Adrenal Mass Evaluation. For the diagnosis of adenoma versus metastasis, contrast- enhanced MRI does not provide additional information beyond the unenhanced technique. However, MRI without and with IV contrast may be considered if there is concern for pheochromocytoma or hypervascular metastasis, as the contrast can show the typical bright enhancement of this lesion. Contrast can also confirm lack of enhancement of a cystic lesion. In patients with a history of malignancy, Candel et al [11] found that 87% of lesions <3 cm were benign and that >95% of lesions >3 cm were malignant. In a similar population, Lee et al [35] found that 79% of lesions <2.5 cm were benign. Van Erkel et al [67] in a mixed population showed that a threshold of 3.1 cm discriminated 93% of lesions. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET can be used to identify metastases in oncologic patients in various cancers [26,77-79]. FDG-PET is sensitive to metabolically active lesions, and metastases usually show greater uptake than benign lesions. In several studies, there have been a few false-positives with FDG-PET, lowering specificity to 85% in one study [80], but excellent sensitivity has been achieved [26,77-79]. False-negative scans have occurred in renal cell carcinoma metastases [64]. SUVs are typically greater for metastatic disease [21]. However, mild activity can be seen in benign adenomas (typically less than background liver), thus potentially leading to false-positive interpretations. Studies have predominantly evaluated FDG-PET or FDG-PET/CT in the oncologic population. However, Tessonnier et al [44] evaluated 41 adrenal tumors in 37 patients who had no history of malignancy using FDG-PET/CT. All tumors were without diagnostically benign features on CT or MRI. In this small series, a tumor/liver SUVmax ratio >1.8 yielded 100% sensitivity and specificity for malignancy. 11C-metomidate has been found to localize in adrenocortical tumors and is useful for determining whether a tumor is of adrenocortical origin.

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Typical treatment goals include identification of the causative disease process to facilitate therapy, recovery, and improvement of dyspnea symptoms. Initial diagnostic evaluation is centered about careful history taking and physical examination [1]. Physical examination findings in cardiac causes of dyspnea could include murmurs (eg, systolic murmurs in the setting of valve insufficiency) as well as an abnormality in heart rate or rhythm, extra heart sounds (S3 in setting of ventricular dysfunction, pericardial knock associated with constriction), or jugular vein distention and edema in heart failure. A nuanced accounting of relevant physical examination findings and history is beyond the scope of this document. Diagnostic investigation may be supplemented by chest radiography and electrocardiography (ECG) as well as laboratory testing. However, identifying the cause of dyspnea in some cases remains elusive [7], and advanced diagnostic imaging may play a critical role in the care of these patients. Special Imaging Considerations MRI imaging artifacts in patients with implanted electronic devices [8-11] and arrhythmias [12-14] can be mitigated with use of evolving imaging techniques. Point-of-care scanning with pocket echocardiography has improved time to definitive treatment (83 versus 180 days) and has been associated with improved outcomes, 15% versus 28% hospitalization or death, in a prospective randomized trial involving 253 patients in resource limited areas [15], whereas point-of-care echocardiography scanning with standard equipment obviated the need for formal scans in community patients with asymptomatic murmurs [16], with 100% of abnormalities identified on a point-of-care scan in 175 patients. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels.

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . Typical treatment goals include identification of the causative disease process to facilitate therapy, recovery, and improvement of dyspnea symptoms. Initial diagnostic evaluation is centered about careful history taking and physical examination [1]. Physical examination findings in cardiac causes of dyspnea could include murmurs (eg, systolic murmurs in the setting of valve insufficiency) as well as an abnormality in heart rate or rhythm, extra heart sounds (S3 in setting of ventricular dysfunction, pericardial knock associated with constriction), or jugular vein distention and edema in heart failure. A nuanced accounting of relevant physical examination findings and history is beyond the scope of this document. Diagnostic investigation may be supplemented by chest radiography and electrocardiography (ECG) as well as laboratory testing. However, identifying the cause of dyspnea in some cases remains elusive [7], and advanced diagnostic imaging may play a critical role in the care of these patients. Special Imaging Considerations MRI imaging artifacts in patients with implanted electronic devices [8-11] and arrhythmias [12-14] can be mitigated with use of evolving imaging techniques. Point-of-care scanning with pocket echocardiography has improved time to definitive treatment (83 versus 180 days) and has been associated with improved outcomes, 15% versus 28% hospitalization or death, in a prospective randomized trial involving 253 patients in resource limited areas [15], whereas point-of-care echocardiography scanning with standard equipment obviated the need for formal scans in community patients with asymptomatic murmurs [16], with 100% of abnormalities identified on a point-of-care scan in 175 patients. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels.

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Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] All elements are essential: 1) timing, 2) reconstructions/reformats, and 3) 3-D renderings. Standard CTs with contrast also include timing issues and reconstructions/reformats. Only in CTA, however, is 3-D rendering a required element. This corresponds to the definitions that the CMS has applied to the Current Procedural Terminology codes. OR Discussion of Procedures by Variant Variant 1: Dyspnea due to suspected valvular heart disease. Ischemia excluded. Initial imaging. Arteriography Coronary with Ventriculography There is no relevant literature to support the use of arteriography coronary with ventriculography for the evaluation of dyspnea due to suspected VHD, ischemia excluded. CT Coronary Calcium There is scant literature regarding the use of CT coronary calcium scans in the evaluation of dyspnea due to suspected VHD, ischemia excluded. Presence of mitral annular calcification on CT coronary calcium scans has shown correlation with cardiovascular risk [20]. Coronary artery calcium scanning for the detection and quantification of aortic valve calcium burden may be useful in some instances, for example, in patients with low- gradient aortic stenosis, but is not a first-line imaging examination. CT Heart Function and Morphology CT plays a predominantly supportive role to echocardiography in the assessment of suspected VHD, utilized when echocardiographic images are suboptimal, or to provide complementary information [21]. CT can aid in differentiating aortic leaflet morphologies, with leaflet fusion length, uneven cusp area, and midline calcification all showing strong association with bicuspid valve (P < .

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] All elements are essential: 1) timing, 2) reconstructions/reformats, and 3) 3-D renderings. Standard CTs with contrast also include timing issues and reconstructions/reformats. Only in CTA, however, is 3-D rendering a required element. This corresponds to the definitions that the CMS has applied to the Current Procedural Terminology codes. OR Discussion of Procedures by Variant Variant 1: Dyspnea due to suspected valvular heart disease. Ischemia excluded. Initial imaging. Arteriography Coronary with Ventriculography There is no relevant literature to support the use of arteriography coronary with ventriculography for the evaluation of dyspnea due to suspected VHD, ischemia excluded. CT Coronary Calcium There is scant literature regarding the use of CT coronary calcium scans in the evaluation of dyspnea due to suspected VHD, ischemia excluded. Presence of mitral annular calcification on CT coronary calcium scans has shown correlation with cardiovascular risk [20]. Coronary artery calcium scanning for the detection and quantification of aortic valve calcium burden may be useful in some instances, for example, in patients with low- gradient aortic stenosis, but is not a first-line imaging examination. CT Heart Function and Morphology CT plays a predominantly supportive role to echocardiography in the assessment of suspected VHD, utilized when echocardiographic images are suboptimal, or to provide complementary information [21]. CT can aid in differentiating aortic leaflet morphologies, with leaflet fusion length, uneven cusp area, and midline calcification all showing strong association with bicuspid valve (P < .

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05) [22], with the valve type characterized on surface echocardiography often (20%) reclassified after tomographic imaging with MRI, CT, or transesophageal echocardiography (TEE) [23]. CT may provide additional insight in the setting of suspected mechanical prosthetic valve dysfunction [24] and can also provide precise concomitant anatomic delineation of the entire aorta. CT is increasingly utilized as part of a comprehensive preprocedural preparation for VHD interventions. CT imaging of cardiac and vascular structures plays a critical role in the planning of transcatheter aortic valve Dyspnea-Suspected Cardiac Origin replacement [25], and up to 30.9% and 32.6% of those with suspect clinical and echocardiographic findings posttranscatheter aortic valve replacement or surgical aortic valve repair, respectively [26]. CT imaging is increasingly utilized in planning transcatheter interventions for valvular and structural heart disease beyond the aortic valve [27-29] as well as planning, risk stratification, and follow-up of surgical interventions for VHD [26]. Epicardial fat as assessed on CT has shown correlation with mitral annular and aortic leaflet calcification [30], although this is not routinely employed in clinical practice. CTA Coronary Arteries There is no relevant literature to support the use of CTA coronary arteries for the evaluation of dyspnea due to suspected VHD, ischemia excluded. Coronary ostia heights relative to aortic annulus are assessed on CTA as part of transcatheter aortic valve planning [25]. FDG-PET/CT Heart There is no relevant literature to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT heart for the evaluation of dyspnea due to suspected VHD, ischemia excluded. MRI Heart Function and Morphology MRI plays a complementary role to echocardiography in the assessment of suspected VHD.

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . 05) [22], with the valve type characterized on surface echocardiography often (20%) reclassified after tomographic imaging with MRI, CT, or transesophageal echocardiography (TEE) [23]. CT may provide additional insight in the setting of suspected mechanical prosthetic valve dysfunction [24] and can also provide precise concomitant anatomic delineation of the entire aorta. CT is increasingly utilized as part of a comprehensive preprocedural preparation for VHD interventions. CT imaging of cardiac and vascular structures plays a critical role in the planning of transcatheter aortic valve Dyspnea-Suspected Cardiac Origin replacement [25], and up to 30.9% and 32.6% of those with suspect clinical and echocardiographic findings posttranscatheter aortic valve replacement or surgical aortic valve repair, respectively [26]. CT imaging is increasingly utilized in planning transcatheter interventions for valvular and structural heart disease beyond the aortic valve [27-29] as well as planning, risk stratification, and follow-up of surgical interventions for VHD [26]. Epicardial fat as assessed on CT has shown correlation with mitral annular and aortic leaflet calcification [30], although this is not routinely employed in clinical practice. CTA Coronary Arteries There is no relevant literature to support the use of CTA coronary arteries for the evaluation of dyspnea due to suspected VHD, ischemia excluded. Coronary ostia heights relative to aortic annulus are assessed on CTA as part of transcatheter aortic valve planning [25]. FDG-PET/CT Heart There is no relevant literature to support the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT heart for the evaluation of dyspnea due to suspected VHD, ischemia excluded. MRI Heart Function and Morphology MRI plays a complementary role to echocardiography in the assessment of suspected VHD.

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MRI may be utilized when echocardiographic images are suboptimal or to provide additional quantitative flow information with use of phase-contrast velocity encoded sequences. MRI offers multiplanar capacity in demonstration of leaflet morphology and motion and is less dependent upon patient anatomy than echocardiography. However, MRI requires multiple cardiac cycles for data collection, and imaging may be compromised in cases of arrhythmia, whereas echocardiography offers real-time valve morphologic assessment and is more mobile. MRI often shows lower peak velocities than Doppler US; however, mean flow is more accurately analyzed with phase-contrast techniques that account for variation in flow across a vessel diameter. MRI may be preferred over echocardiography in the assessment of the pulmonary valve and can be used to grade mitral, pulmonic, or aortic regurgitation if there is clinical uncertainty after echocardiography [21]. The assessment of regurgitant volume, left ventricular (LV) volume, and myocardial fibrosis may play an eventual role in risk prognosis in VHD. MRI quantified aortic insufficiency has shown correlation with surgical repair, with 85% of patients having regurgitant fraction >33% progressing to surgery, typically in <3 years [31]. Discordance between echocardiographic and MRI assessment of mitral insufficiency has been reported (r = 0.6), with MRI predicting postsurgical LV remodeling more accurately (r = 0.85, P < . 0001) than echocardiography (r = 0.32; P = . 1) in a prospective multicenter trial [32]. MRI provides high inter- and intrareader reproducibility [33] with semiautomated flow measurement in the ascending aorta and main pulmonary artery.

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . MRI may be utilized when echocardiographic images are suboptimal or to provide additional quantitative flow information with use of phase-contrast velocity encoded sequences. MRI offers multiplanar capacity in demonstration of leaflet morphology and motion and is less dependent upon patient anatomy than echocardiography. However, MRI requires multiple cardiac cycles for data collection, and imaging may be compromised in cases of arrhythmia, whereas echocardiography offers real-time valve morphologic assessment and is more mobile. MRI often shows lower peak velocities than Doppler US; however, mean flow is more accurately analyzed with phase-contrast techniques that account for variation in flow across a vessel diameter. MRI may be preferred over echocardiography in the assessment of the pulmonary valve and can be used to grade mitral, pulmonic, or aortic regurgitation if there is clinical uncertainty after echocardiography [21]. The assessment of regurgitant volume, left ventricular (LV) volume, and myocardial fibrosis may play an eventual role in risk prognosis in VHD. MRI quantified aortic insufficiency has shown correlation with surgical repair, with 85% of patients having regurgitant fraction >33% progressing to surgery, typically in <3 years [31]. Discordance between echocardiographic and MRI assessment of mitral insufficiency has been reported (r = 0.6), with MRI predicting postsurgical LV remodeling more accurately (r = 0.85, P < . 0001) than echocardiography (r = 0.32; P = . 1) in a prospective multicenter trial [32]. MRI provides high inter- and intrareader reproducibility [33] with semiautomated flow measurement in the ascending aorta and main pulmonary artery.

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Although CT and echocardiography are most commonly used for planning and follow-up of structural and VHD interventions, MRI is playing an increasing role in this expanding field [35], capitalizing on the good spatial and temporal resolution, large field of view, and inherent tissue characterization available with MRI. Dyspnea-Suspected Cardiac Origin MRI Heart Function with Stress There is no relevant literature to support the use of MRI heart function with stress for the evaluation of dyspnea due to suspected VHD, ischemia excluded. Radiography Chest Chest radiography can provide information on heart failure in the setting of VHD. Diagnosis of specific valve abnormalities is limited, but radiographs may aid in identification of characteristic cardiac chamber and great vessel changes [44] as well as marked calcification of aortic root or mitral annulus. Rb-82 PET/CT Heart There is no relevant literature to support the use of Rb-82 PET/CT heart for the evaluation of dyspnea due to suspected VHD, ischemia excluded. SPECT or SPECT/CT MPI Rest and Stress There is no relevant literature to support the use of single-photon emission computed tomography (SPECT) or SPECT/CT myocardial perfusion imaging (MPI) for the evaluation of dyspnea due to suspected VHD, ischemia excluded. US Echocardiography Transthoracic Resting TTE is the primary modality for diagnosis, assessment, and follow-up of native and prosthetic VHD [21,48], providing insights to anatomy, mechanism of disease, and hemodynamic impact. Evaluation of leaflet morphology is typically obtained first by echocardiography, with proposed schemes to distinguish unicuspid from bicuspid or tricuspid aortic valves [49], although there is reported a common (20%) reclassification of leaflet morphology as determined on surface echocardiography after MRI, CT, or TEE imaging [23], or internal review of echocardiography images [50].

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . Although CT and echocardiography are most commonly used for planning and follow-up of structural and VHD interventions, MRI is playing an increasing role in this expanding field [35], capitalizing on the good spatial and temporal resolution, large field of view, and inherent tissue characterization available with MRI. Dyspnea-Suspected Cardiac Origin MRI Heart Function with Stress There is no relevant literature to support the use of MRI heart function with stress for the evaluation of dyspnea due to suspected VHD, ischemia excluded. Radiography Chest Chest radiography can provide information on heart failure in the setting of VHD. Diagnosis of specific valve abnormalities is limited, but radiographs may aid in identification of characteristic cardiac chamber and great vessel changes [44] as well as marked calcification of aortic root or mitral annulus. Rb-82 PET/CT Heart There is no relevant literature to support the use of Rb-82 PET/CT heart for the evaluation of dyspnea due to suspected VHD, ischemia excluded. SPECT or SPECT/CT MPI Rest and Stress There is no relevant literature to support the use of single-photon emission computed tomography (SPECT) or SPECT/CT myocardial perfusion imaging (MPI) for the evaluation of dyspnea due to suspected VHD, ischemia excluded. US Echocardiography Transthoracic Resting TTE is the primary modality for diagnosis, assessment, and follow-up of native and prosthetic VHD [21,48], providing insights to anatomy, mechanism of disease, and hemodynamic impact. Evaluation of leaflet morphology is typically obtained first by echocardiography, with proposed schemes to distinguish unicuspid from bicuspid or tricuspid aortic valves [49], although there is reported a common (20%) reclassification of leaflet morphology as determined on surface echocardiography after MRI, CT, or TEE imaging [23], or internal review of echocardiography images [50].

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Bicuspid leaflet morphology as identified on echocardiography can predict valvular function and aortic dilation [51], with a prospective group of 852 patients with bicuspid valve having aortic regurgitation (23%) related to valve prolapse (OR: 5.16, P < . 0001), and aortic stenosis (22%) associated with fused right and noncusps, (OR: 2.09, P < . 001), and the presence of raphe (OR: 2.75, P < 0.001). Gradation of valve abnormality (eg, mild, moderate, or severe aortic stenosis) is predominantly obtained by echocardiography. Echocardiographic assessment of early bioprosthetic valve failure can be addressed systematically with correlation to surgical changes [52]. Patient prosthesis mismatch has been associated with raised transprosthetic pressure after mitral valve replacement, although only when calculated by the continuity equation (P = . 021) [53]. Doppler parameters may be useful in estimating LV filling pressure in patients with mitral annular calcification [54]; in a group of 50 patients with mitral annular calcification, the ratio of early-to-late diastolic filling velocity (mitral E/A) showed the best correlation, (r = 0.66; P < . 001), whereas the ratio of early diastolic filling velocity-to-mitral annulus velocity (E/e') demonstrated weak correlation (r = 0.42; P = . 003). Large-scale screening of populations revealed newly identified VHD in 51% of 2,500 patients >65 years of age, although this was commonly mild [55], with cardiac auscultation by general practitioners showing modest sensitivity and specificity (44% and 69% , respectively) in asymptomatic patients, even in the setting of significant disease [56]. TTE 3-D techniques may improve assessment of mitral or aortic valve dysfunction, with a systematic review showing the strongest evidence for estimating the mitral valve area in patients with rheumatic mitral valve stenosis and the vena contracta area in patients with mitral insufficiency [57].

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . Bicuspid leaflet morphology as identified on echocardiography can predict valvular function and aortic dilation [51], with a prospective group of 852 patients with bicuspid valve having aortic regurgitation (23%) related to valve prolapse (OR: 5.16, P < . 0001), and aortic stenosis (22%) associated with fused right and noncusps, (OR: 2.09, P < . 001), and the presence of raphe (OR: 2.75, P < 0.001). Gradation of valve abnormality (eg, mild, moderate, or severe aortic stenosis) is predominantly obtained by echocardiography. Echocardiographic assessment of early bioprosthetic valve failure can be addressed systematically with correlation to surgical changes [52]. Patient prosthesis mismatch has been associated with raised transprosthetic pressure after mitral valve replacement, although only when calculated by the continuity equation (P = . 021) [53]. Doppler parameters may be useful in estimating LV filling pressure in patients with mitral annular calcification [54]; in a group of 50 patients with mitral annular calcification, the ratio of early-to-late diastolic filling velocity (mitral E/A) showed the best correlation, (r = 0.66; P < . 001), whereas the ratio of early diastolic filling velocity-to-mitral annulus velocity (E/e') demonstrated weak correlation (r = 0.42; P = . 003). Large-scale screening of populations revealed newly identified VHD in 51% of 2,500 patients >65 years of age, although this was commonly mild [55], with cardiac auscultation by general practitioners showing modest sensitivity and specificity (44% and 69% , respectively) in asymptomatic patients, even in the setting of significant disease [56]. TTE 3-D techniques may improve assessment of mitral or aortic valve dysfunction, with a systematic review showing the strongest evidence for estimating the mitral valve area in patients with rheumatic mitral valve stenosis and the vena contracta area in patients with mitral insufficiency [57].

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Echocardiography has provided mechanistic clarification to tricuspid valve insufficiency induced by device leads; notably, when the lead tip was in the interventricular septum or if the lead was shown to be impinging on a leaflet, the device lead was more likely to impede leaflet mobility (P < . 05), and interfering leads were associated with more significant tricuspid regurgitation than noninterfering leads (P < . 05) [58]. Echocardiographic assessment of the left atrium may improve insights to aortic and mitral valve dysfunction [59]. Dyspnea-Suspected Cardiac Origin Novel strain imaging applications have shown promise in characterizing LV changes in patients with aortic stenosis and aortic insufficiency [60]. Volume loop characteristics (area under receiver operating characteristic curve [AUC] = 0.99, 1.00, and 1.00; all P < . 01) showed improved discrimination relative to peak strain (AUC = 0.75, 0.89, and 0.76; P = . 06, <. 01, and . 08, respectively) and LV ejection fraction (AUC = 0.56, 0.69 and 0.69; all P > . 05) to distinguish aortic valve stenosis versus control, aortic valve regurgitation versus control, and aortic valve stenosis versus aortic valve regurgitation groups, respectively. Strain imaging has also shown promise in providing improved insight to aortopathy and aortic elasticity in patients with a bicuspid valve [61]. US Echocardiography Transthoracic Stress TTE stress may be useful in further characterization of mitral and aortic stenosis, for example, in setting of discrepant resting echocardiographic gradation of stenosis and patient symptoms [21,24], as well as evaluating symptoms and exercise capacity of patients. Stress echocardiography may be useful in determining eligibility for competitive sports [62], with exercise-induced changes to ventricular response and valvular lesion, as well as changes to right ventricular (RV) systolic pressure potentially aiding in decision making.

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . Echocardiography has provided mechanistic clarification to tricuspid valve insufficiency induced by device leads; notably, when the lead tip was in the interventricular septum or if the lead was shown to be impinging on a leaflet, the device lead was more likely to impede leaflet mobility (P < . 05), and interfering leads were associated with more significant tricuspid regurgitation than noninterfering leads (P < . 05) [58]. Echocardiographic assessment of the left atrium may improve insights to aortic and mitral valve dysfunction [59]. Dyspnea-Suspected Cardiac Origin Novel strain imaging applications have shown promise in characterizing LV changes in patients with aortic stenosis and aortic insufficiency [60]. Volume loop characteristics (area under receiver operating characteristic curve [AUC] = 0.99, 1.00, and 1.00; all P < . 01) showed improved discrimination relative to peak strain (AUC = 0.75, 0.89, and 0.76; P = . 06, <. 01, and . 08, respectively) and LV ejection fraction (AUC = 0.56, 0.69 and 0.69; all P > . 05) to distinguish aortic valve stenosis versus control, aortic valve regurgitation versus control, and aortic valve stenosis versus aortic valve regurgitation groups, respectively. Strain imaging has also shown promise in providing improved insight to aortopathy and aortic elasticity in patients with a bicuspid valve [61]. US Echocardiography Transthoracic Stress TTE stress may be useful in further characterization of mitral and aortic stenosis, for example, in setting of discrepant resting echocardiographic gradation of stenosis and patient symptoms [21,24], as well as evaluating symptoms and exercise capacity of patients. Stress echocardiography may be useful in determining eligibility for competitive sports [62], with exercise-induced changes to ventricular response and valvular lesion, as well as changes to right ventricular (RV) systolic pressure potentially aiding in decision making.

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Variant 2: Dyspnea due to suspected cardiac arrhythmia. Ischemia excluded. Initial imaging. Arteriography Coronary with Ventriculography There is no relevant literature to support the use of arteriography coronary with ventriculography for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. CT Coronary Calcium There is no relevant literature to support the use of CT coronary calcium for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. CT can provide a precise regional anatomic survey for pre- and intraprocedural guidance of catheter ablation [66], with potential ablation targets notably located within 1 cm of critical structures such as coronary arteries and phrenic nerve in 35 (80%) and 18 (37%) patients, respectively [68]. CT also provides robust anatomic delineation of pulmonary vein and left atrial appendage anatomy [28] for both planning and follow-up of pulmonary vein ablation as well as left atrial appendage occlusion for atrial fibrillation treatment. Measured attenuation of epicardial fat has shown to be a predictor of electrophysiologic properties of the adjacent left atrium in patients with atrial fibrillation [69]. CTA Coronary Arteries There is no relevant literature to support the use of CTA coronary arteries for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. FDG-PET/CT Heart Patients may benefit from PET imaging for scar identification and for prediction of ventricular arrhythmia and sudden cardiac death. Full thickness myocardial scarring has shown strong association with major arrhythmic events after accounting for age, sex, cardiovascular risk factors, beta-blocker therapy, and resting LV ejection fraction Morphologic analysis of fibrotic scarring in nonischemic dilated cardiomyopathy has shown promise in prediction of electrophysiologic impact [77].

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . Variant 2: Dyspnea due to suspected cardiac arrhythmia. Ischemia excluded. Initial imaging. Arteriography Coronary with Ventriculography There is no relevant literature to support the use of arteriography coronary with ventriculography for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. CT Coronary Calcium There is no relevant literature to support the use of CT coronary calcium for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. CT can provide a precise regional anatomic survey for pre- and intraprocedural guidance of catheter ablation [66], with potential ablation targets notably located within 1 cm of critical structures such as coronary arteries and phrenic nerve in 35 (80%) and 18 (37%) patients, respectively [68]. CT also provides robust anatomic delineation of pulmonary vein and left atrial appendage anatomy [28] for both planning and follow-up of pulmonary vein ablation as well as left atrial appendage occlusion for atrial fibrillation treatment. Measured attenuation of epicardial fat has shown to be a predictor of electrophysiologic properties of the adjacent left atrium in patients with atrial fibrillation [69]. CTA Coronary Arteries There is no relevant literature to support the use of CTA coronary arteries for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. FDG-PET/CT Heart Patients may benefit from PET imaging for scar identification and for prediction of ventricular arrhythmia and sudden cardiac death. Full thickness myocardial scarring has shown strong association with major arrhythmic events after accounting for age, sex, cardiovascular risk factors, beta-blocker therapy, and resting LV ejection fraction Morphologic analysis of fibrotic scarring in nonischemic dilated cardiomyopathy has shown promise in prediction of electrophysiologic impact [77].

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In a group of patients with systemic sclerosis, extracellular volume as measured on MRI corresponded with a risk for significant arrhythmia [78]. In a group of cardiac resynchronization therapy patients, an algorithm based on scar mass as quantitated by MRI identified 148 patients (68.2%) without implantable cardioverter-defibrillator therapy/sudden cardiac death during follow-up with a 100% negative predictive value [79], and appropriate implantable cardioverter-defibrillator therapy can be predicted in ischemic cardiomyopathy patients with primary prevention implantable cardioverter-defibrillator by quantifying the LGE border zone [80]. Concomitant assessment for structural heart disease and LV function can also be obtained. MRI can provide tissue-specific direction for targeted treatment of both ventricular and atrial arrhythmic foci [81,82]. Morphologic and functional criteria as assessed by MRI are useful in cases of suspected ARVC/D [83]. MRI Heart Function with Stress There is no relevant literature to support the use of MRI heart function with stress for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. Radiography Chest There is no relevant literature to support the use of radiography for the evaluation of dyspnea due to suspected arrhythmia, ischemia excluded. Radiography may demonstrate cardiac silhouette enlargement as well as pulmonary vascular cephalization or edema as may be seen in setting of cardiac arrhythmia. Rb-82 PET/CT Heart There is no relevant literature to support the use of Rb-82 PET/CT heart for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. SPECT or SPECT/CT MPI Rest and Stress There is scant literature regarding the use of SPECT or SPECT/CT MPI in the assessment of suspected arrhythmia.

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . In a group of patients with systemic sclerosis, extracellular volume as measured on MRI corresponded with a risk for significant arrhythmia [78]. In a group of cardiac resynchronization therapy patients, an algorithm based on scar mass as quantitated by MRI identified 148 patients (68.2%) without implantable cardioverter-defibrillator therapy/sudden cardiac death during follow-up with a 100% negative predictive value [79], and appropriate implantable cardioverter-defibrillator therapy can be predicted in ischemic cardiomyopathy patients with primary prevention implantable cardioverter-defibrillator by quantifying the LGE border zone [80]. Concomitant assessment for structural heart disease and LV function can also be obtained. MRI can provide tissue-specific direction for targeted treatment of both ventricular and atrial arrhythmic foci [81,82]. Morphologic and functional criteria as assessed by MRI are useful in cases of suspected ARVC/D [83]. MRI Heart Function with Stress There is no relevant literature to support the use of MRI heart function with stress for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. Radiography Chest There is no relevant literature to support the use of radiography for the evaluation of dyspnea due to suspected arrhythmia, ischemia excluded. Radiography may demonstrate cardiac silhouette enlargement as well as pulmonary vascular cephalization or edema as may be seen in setting of cardiac arrhythmia. Rb-82 PET/CT Heart There is no relevant literature to support the use of Rb-82 PET/CT heart for the evaluation of dyspnea due to suspected cardiac arrhythmia, ischemia excluded. SPECT or SPECT/CT MPI Rest and Stress There is scant literature regarding the use of SPECT or SPECT/CT MPI in the assessment of suspected arrhythmia.

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Dyspnea Suspected Cardiac Origin Ischemia Already Excluded

MPI can elucidate remodeling in patients who are postcardiac resynchronization therapy, with differential incidence of ventricular arrhythmia [84], and gated SPECT imaging phase analysis has shown potential in differentiating degrees of mechanical dyssynchrony [85]. Dyspnea-Suspected Cardiac Origin US Echocardiography Transesophageal There is scant literature regarding the use of TEE in the assessment of suspected arrhythmia. Left atrial appendage size (left atrial appendage end-diastolic volume [P = . 002; OR 1.6] and morphology [cauliflower shape (P = . 001; OR, 10.2)]) are predictive of thromboembolic events in patients with nonvalvular atrial fibrillation [86]. US Echocardiography Transthoracic Resting Echocardiography is an important noninvasive imaging technique in the diagnosis and prognosis of patients with arrhythmias, providing insight into associated myocardial, valvular, and structural disorders. Morphologic and functional criteria are useful in RV assessment in cases of suspected ARVC/D [83]. Assessment of LV function by speckle-tracking strain assessment has shown utility in prediction of ventricular arrhythmia in patients post-LV assist devices placement [87], and ejection fraction as assessed by echocardiography has shown predictive value in ventricular arrhythmia as well as in all-cause mortality in heart failure patients with implantable cardioverter- defibrillators [88]. Although epicardial fat is rarely noted on clinical reports, associations have been noted between epicardial fat thickness as measured on echocardiography and dysrhythmia [94], in the prediction of successful electrical cardioversion and atrial fibrillation recurrence [95,96], and in the ablation of premature ventricular contractions [97]. Measurement of left atrial volume has shown to be a predictor of persistent atrial fibrillation after mitral valve surgery, with indexed volume >39 mL/m2 having a sensitivity of 79% (AUC: 0.762, SE: 0.051, P < . 001) [98].

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . MPI can elucidate remodeling in patients who are postcardiac resynchronization therapy, with differential incidence of ventricular arrhythmia [84], and gated SPECT imaging phase analysis has shown potential in differentiating degrees of mechanical dyssynchrony [85]. Dyspnea-Suspected Cardiac Origin US Echocardiography Transesophageal There is scant literature regarding the use of TEE in the assessment of suspected arrhythmia. Left atrial appendage size (left atrial appendage end-diastolic volume [P = . 002; OR 1.6] and morphology [cauliflower shape (P = . 001; OR, 10.2)]) are predictive of thromboembolic events in patients with nonvalvular atrial fibrillation [86]. US Echocardiography Transthoracic Resting Echocardiography is an important noninvasive imaging technique in the diagnosis and prognosis of patients with arrhythmias, providing insight into associated myocardial, valvular, and structural disorders. Morphologic and functional criteria are useful in RV assessment in cases of suspected ARVC/D [83]. Assessment of LV function by speckle-tracking strain assessment has shown utility in prediction of ventricular arrhythmia in patients post-LV assist devices placement [87], and ejection fraction as assessed by echocardiography has shown predictive value in ventricular arrhythmia as well as in all-cause mortality in heart failure patients with implantable cardioverter- defibrillators [88]. Although epicardial fat is rarely noted on clinical reports, associations have been noted between epicardial fat thickness as measured on echocardiography and dysrhythmia [94], in the prediction of successful electrical cardioversion and atrial fibrillation recurrence [95,96], and in the ablation of premature ventricular contractions [97]. Measurement of left atrial volume has shown to be a predictor of persistent atrial fibrillation after mitral valve surgery, with indexed volume >39 mL/m2 having a sensitivity of 79% (AUC: 0.762, SE: 0.051, P < . 001) [98].

69407

acrac_69407_10

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded

US Echocardiography Transthoracic Stress There is no relevant literature to support the use of TTE stress for the evaluation of dyspnea due to suspected arrhythmia, ischemia excluded. Variant 3: Dyspnea due to suspected pericardial disease. Ischemia excluded. Initial imaging. Arteriography Coronary with Ventriculography There is no relevant literature to support the use of arteriography coronary with ventriculography for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. This is distinguished from right heart catheterization. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. CT Chest With IV Contrast There is no relevant literature to support the use of CT chest with IV contrast for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. Although this procedure is not a first-line imaging test, it may provide information on pericardial changes such as effusion, thickening, or enhancement. Dyspnea-Suspected Cardiac Origin CT Coronary Calcium There is no relevant literature to support the use of CT coronary calcium for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. CT Heart Function and Morphology CT is useful in depiction of abnormal pericardial thickening as well as in defining the extent of pericardial calcification [100]. CT can be considered for assessing size, location, and density of pericardial effusion, which may not be fully demonstrated by echocardiography, and can be used for planning before pericardiocentesis or pericardial cardiectomy. In cases of suspected pericardial masses or tumors, CT can be used for assessment of size and location, involvement or invasion of adjacent structures, and extracardiac findings such as lymphadenopathy [101].

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . US Echocardiography Transthoracic Stress There is no relevant literature to support the use of TTE stress for the evaluation of dyspnea due to suspected arrhythmia, ischemia excluded. Variant 3: Dyspnea due to suspected pericardial disease. Ischemia excluded. Initial imaging. Arteriography Coronary with Ventriculography There is no relevant literature to support the use of arteriography coronary with ventriculography for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. This is distinguished from right heart catheterization. CT Chest Without and With IV Contrast There is no relevant literature to support the use of CT chest without and with IV contrast for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. CT Chest With IV Contrast There is no relevant literature to support the use of CT chest with IV contrast for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. Although this procedure is not a first-line imaging test, it may provide information on pericardial changes such as effusion, thickening, or enhancement. Dyspnea-Suspected Cardiac Origin CT Coronary Calcium There is no relevant literature to support the use of CT coronary calcium for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. CT Heart Function and Morphology CT is useful in depiction of abnormal pericardial thickening as well as in defining the extent of pericardial calcification [100]. CT can be considered for assessing size, location, and density of pericardial effusion, which may not be fully demonstrated by echocardiography, and can be used for planning before pericardiocentesis or pericardial cardiectomy. In cases of suspected pericardial masses or tumors, CT can be used for assessment of size and location, involvement or invasion of adjacent structures, and extracardiac findings such as lymphadenopathy [101].

69407

acrac_69407_11

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded

CT provides limited and indirect hemodynamic information, such as enlargement of the atria and venae cavae in cases of pericardial constriction. Functional evaluation using CT is possible using retrospective ECG-gated examination, although the utility of such techniques are challenged by breath-held acquisition, suboptimal temporal resolution compared to echocardiography, and MRI as well as the potential increased artifact case of tachycardia or unstable heart rhythm [100,102]. Epicardial fat volume quantitation by CT has shown some association with the outcome of patients with a first episode of acute pericarditis and a potential prognostic implication [103], although this has limited clinical application to date. CTA Chest There is no relevant literature to support the use of CTA chest for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. Although this procedure is not a first-line imaging test, it may provide information on pericardial changes such as effusion, thickening, or enhancement. CTA Coronary Arteries There is no relevant literature to support the use of CTA coronary arteries for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. FDG-PET/CT Heart There is limited literature regarding the use of FDG-PET/CT in the assessment of suspected pericardial disease, ischemia excluded. The presence of pericardial inflammation as stratified by standardized uptake values can predict reversibility of transient constrictive pericarditis with medical treatment. Using pericardial maximized standardized uptake value of 3.0 as a cutoff value, sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET/CT for predicting response to medical treatment were 100%, 71%, 82%, and 100%, respectively, in a small group (n = 16) of prospectively recruited patients with constrictive pericarditis [104].

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . CT provides limited and indirect hemodynamic information, such as enlargement of the atria and venae cavae in cases of pericardial constriction. Functional evaluation using CT is possible using retrospective ECG-gated examination, although the utility of such techniques are challenged by breath-held acquisition, suboptimal temporal resolution compared to echocardiography, and MRI as well as the potential increased artifact case of tachycardia or unstable heart rhythm [100,102]. Epicardial fat volume quantitation by CT has shown some association with the outcome of patients with a first episode of acute pericarditis and a potential prognostic implication [103], although this has limited clinical application to date. CTA Chest There is no relevant literature to support the use of CTA chest for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. Although this procedure is not a first-line imaging test, it may provide information on pericardial changes such as effusion, thickening, or enhancement. CTA Coronary Arteries There is no relevant literature to support the use of CTA coronary arteries for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. FDG-PET/CT Heart There is limited literature regarding the use of FDG-PET/CT in the assessment of suspected pericardial disease, ischemia excluded. The presence of pericardial inflammation as stratified by standardized uptake values can predict reversibility of transient constrictive pericarditis with medical treatment. Using pericardial maximized standardized uptake value of 3.0 as a cutoff value, sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET/CT for predicting response to medical treatment were 100%, 71%, 82%, and 100%, respectively, in a small group (n = 16) of prospectively recruited patients with constrictive pericarditis [104].

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acrac_69407_12

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded

FDG-PET/CT may be helpful in making a presumptive diagnosis of malignancy, especially in nondiagnostic pericardial effusion with relatively high-risk pericardiocentesis, or may guide selection of an optimal biopsy site with a potential high yield of disease. However, infectious processes such as tuberculosis can show increased FDG uptake mimicking malignancy, which limits FDG-PET/CT utility in differentiation between benign and malignant pericardial disease [105]. MRI Heart Function and Morphology MRI is typically an adjuvant test when echocardiographic data are ambiguous or inconclusive for constriction [102]. MRI can provide reliable depiction of pericardial thickening, typically with dark blood imaging, with prognostic value for patients eventually progressing to surgical resection. Furthermore, cardiac MR, real-time cine imaging with free breathing can suggest constrictive pathophysiology where the septum shifts toward the left ventricle during early inspiration. A model combining pericardial thickness and relative interventricular septal excursion provided the best overall performance in prediction of constrictive pericarditis in a surgical series of patients (C statistic, 0.98, 100% sensitivity, 90% specificity) [106], although shallow breaths or vigorous inspiration may result in false negative or false positive results, respectively [107]. LGE can reveal the presence and severity of pericardial inflammation [102], with histologic changes corresponding to MRI appearance. MRI may define the extent of associated myocarditis when there is a concern of myocardial involvement and echocardiography is inconclusive [107]. MRI can provide incremental value to evaluate the presence and severity of active pericardial inflammation in patients with constrictive pericarditis [107]. Pericardial delayed hyperenhancement quantitative assessment on cardiac MRI can be a helpful prognostic tool in the care of

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . FDG-PET/CT may be helpful in making a presumptive diagnosis of malignancy, especially in nondiagnostic pericardial effusion with relatively high-risk pericardiocentesis, or may guide selection of an optimal biopsy site with a potential high yield of disease. However, infectious processes such as tuberculosis can show increased FDG uptake mimicking malignancy, which limits FDG-PET/CT utility in differentiation between benign and malignant pericardial disease [105]. MRI Heart Function and Morphology MRI is typically an adjuvant test when echocardiographic data are ambiguous or inconclusive for constriction [102]. MRI can provide reliable depiction of pericardial thickening, typically with dark blood imaging, with prognostic value for patients eventually progressing to surgical resection. Furthermore, cardiac MR, real-time cine imaging with free breathing can suggest constrictive pathophysiology where the septum shifts toward the left ventricle during early inspiration. A model combining pericardial thickness and relative interventricular septal excursion provided the best overall performance in prediction of constrictive pericarditis in a surgical series of patients (C statistic, 0.98, 100% sensitivity, 90% specificity) [106], although shallow breaths or vigorous inspiration may result in false negative or false positive results, respectively [107]. LGE can reveal the presence and severity of pericardial inflammation [102], with histologic changes corresponding to MRI appearance. MRI may define the extent of associated myocarditis when there is a concern of myocardial involvement and echocardiography is inconclusive [107]. MRI can provide incremental value to evaluate the presence and severity of active pericardial inflammation in patients with constrictive pericarditis [107]. Pericardial delayed hyperenhancement quantitative assessment on cardiac MRI can be a helpful prognostic tool in the care of

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acrac_69407_13

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded

MRI is useful for assessing pericardial masses and tumors, particularly for accurate localization and sizing and tissue characterization [101,110], and to delineate potential extension to adjacent thoracic anatomic structures. MRI Heart Function with Stress There is no relevant literature to support the use of MRI heart function with stress for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. Radiography Chest Chest radiograph may show suggestive findings of pericardial effusion, pericardial calcifications, pericardial cyst, and pericardial defect/absence, although this generally has a lower diagnostic potential to delineate pericardial abnormities compared with echocardiography, CT, and MRI. Rb-82 PET/CT Heart There is no relevant literature to support the use of Rb-82 PET/CT heart for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. SPECT or SPECT/CT MPI Rest and Stress There is no relevant literature to support the use of SPECT or SPECT/CT MPI rest and stress for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. US Echocardiography Transesophageal TEE can be considered in assessing pericardial disease in a patients with suspected complicated acute pericarditis, constrictive pericarditis, or pericardial masses if TTE images are of poor quality [102]. US Echocardiography Transthoracic Resting TTE is safe and typically considered the first-line imaging modality in almost all types of pericardial diseases [100,102]. Most acute pericarditis cases are uncomplicated, and echocardiography is the first and only imaging test necessary, with diagnosis based on characteristic chest pain and ECG changes. Echocardiography is performed primarily for risk stratification and may identify a pericardial effusion, evidence of pericardial tamponade, wall motion abnormalities, or features of pericardial constriction [102].

Dyspnea Suspected Cardiac Origin Ischemia Already Excluded . MRI is useful for assessing pericardial masses and tumors, particularly for accurate localization and sizing and tissue characterization [101,110], and to delineate potential extension to adjacent thoracic anatomic structures. MRI Heart Function with Stress There is no relevant literature to support the use of MRI heart function with stress for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. Radiography Chest Chest radiograph may show suggestive findings of pericardial effusion, pericardial calcifications, pericardial cyst, and pericardial defect/absence, although this generally has a lower diagnostic potential to delineate pericardial abnormities compared with echocardiography, CT, and MRI. Rb-82 PET/CT Heart There is no relevant literature to support the use of Rb-82 PET/CT heart for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. SPECT or SPECT/CT MPI Rest and Stress There is no relevant literature to support the use of SPECT or SPECT/CT MPI rest and stress for the evaluation of dyspnea due to suspected pericardial disease, ischemia excluded. US Echocardiography Transesophageal TEE can be considered in assessing pericardial disease in a patients with suspected complicated acute pericarditis, constrictive pericarditis, or pericardial masses if TTE images are of poor quality [102]. US Echocardiography Transthoracic Resting TTE is safe and typically considered the first-line imaging modality in almost all types of pericardial diseases [100,102]. Most acute pericarditis cases are uncomplicated, and echocardiography is the first and only imaging test necessary, with diagnosis based on characteristic chest pain and ECG changes. Echocardiography is performed primarily for risk stratification and may identify a pericardial effusion, evidence of pericardial tamponade, wall motion abnormalities, or features of pericardial constriction [102].

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acrac_69372_0

Staging of Renal Cell Carcinoma

Recent advances in the molecular cytogenetics of RCC have significantly enhanced understanding of the pathogenesis, tumor biology, management, and prognosis of this highly heterogeneous malignancy. In 2016, the World Health Organization published the revised classification of renal tumors. There are more than 14 histological subtypes of RCC, but the majority of RCC belong to 3 histological variants, namely clear-cell RCC (75%), papillary RCC (10%-15%), and chromophobe RCC (4%-6%) [3]. Tumor stage is an extremely important prognostic factor in RCC. Patients with stage I localized RCC have an 81% 5-year survival rate compared with just an 8% 5-year survival rate for those with stage IV RCC. Staging of RCC is performed using the TNM staging system, which was developed by the American Joint Committee on Cancer (AJCC) [4]. aThe University of Texas MD Anderson Cancer Center, Houston, Texas. bPanel Chair, UT Southwestern Medical Center, Dallas, Texas. cThe University of Texas MD Anderson Cancer Center, Houston, Texas, Primary care physician. dFeinberg School of Medicine, Northwestern University, Chicago, Illinois; Commission on Nuclear Medicine and Molecular Imaging. eMayo Clinic, Jacksonville, Florida. fUniversity of British Columbia, Vancouver, British Columbia, Canada. gThe University of Texas MD Anderson Cancer Center, Houston, Texas. hDuke University Medical Center, Durham, North Carolina. iThomas Jefferson University Hospital, Philadelphia, Pennsylvania. jMallinckrodt Institute of Radiology Washington University School of Medicine, Saint Louis, Missouri; Commission on Radiation Oncology. kSUNY Upstate Medical University, Syracuse, New York. lPresbyterian Medical Center, University of Pennsylvania, Philadelphia, Pennsylvania; American Urological Association. mCleveland Clinic, Cleveland, Ohio. nUniversity of Alabama at Birmingham, Birmingham, Alabama. oNew York University Langone Medical Center, New York, New York. pSpecialty Chair, Northwestern University, Chicago, Illinois.

Staging of Renal Cell Carcinoma. Recent advances in the molecular cytogenetics of RCC have significantly enhanced understanding of the pathogenesis, tumor biology, management, and prognosis of this highly heterogeneous malignancy. In 2016, the World Health Organization published the revised classification of renal tumors. There are more than 14 histological subtypes of RCC, but the majority of RCC belong to 3 histological variants, namely clear-cell RCC (75%), papillary RCC (10%-15%), and chromophobe RCC (4%-6%) [3]. Tumor stage is an extremely important prognostic factor in RCC. Patients with stage I localized RCC have an 81% 5-year survival rate compared with just an 8% 5-year survival rate for those with stage IV RCC. Staging of RCC is performed using the TNM staging system, which was developed by the American Joint Committee on Cancer (AJCC) [4]. aThe University of Texas MD Anderson Cancer Center, Houston, Texas. bPanel Chair, UT Southwestern Medical Center, Dallas, Texas. cThe University of Texas MD Anderson Cancer Center, Houston, Texas, Primary care physician. dFeinberg School of Medicine, Northwestern University, Chicago, Illinois; Commission on Nuclear Medicine and Molecular Imaging. eMayo Clinic, Jacksonville, Florida. fUniversity of British Columbia, Vancouver, British Columbia, Canada. gThe University of Texas MD Anderson Cancer Center, Houston, Texas. hDuke University Medical Center, Durham, North Carolina. iThomas Jefferson University Hospital, Philadelphia, Pennsylvania. jMallinckrodt Institute of Radiology Washington University School of Medicine, Saint Louis, Missouri; Commission on Radiation Oncology. kSUNY Upstate Medical University, Syracuse, New York. lPresbyterian Medical Center, University of Pennsylvania, Philadelphia, Pennsylvania; American Urological Association. mCleveland Clinic, Cleveland, Ohio. nUniversity of Alabama at Birmingham, Birmingham, Alabama. oNew York University Langone Medical Center, New York, New York. pSpecialty Chair, Northwestern University, Chicago, Illinois.

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acrac_69372_1

Staging of Renal Cell Carcinoma

The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Staging of Renal Cell Carcinoma presence of any nodal metastases (N1) and/ or T3 tumor. Stage IV disease is the presence of any distant metastases (M1) and/or presence of T4 tumor. Curative treatment for RCC may be accomplished with surgical resection. Partial nephrectomy is the preferred treatment option for small T1 RCC, especially because it is associated with lower risk of renal failure and cardiovascular mortality compared to radical nephrectomy. However, it has been reported that incidence of complications such as postoperative bleeding and urinary leaks may be high in partial nephrectomy. Hence, urologists carefully select patients for partial nephrectomy using preoperative scoring systems, such as the Preoperative Aspects and Dimensions Used for Anatomic assessment score, Renal Nephrometry Score, and Centrality Index. Although a full description of these scoring systems is beyond the scope of this manuscript, urologists consider various factors for surgical planning including size of the tumor and the number of lesions (such as presence of multiple and/or bilateral tumors). The location of the tumor is another important criteria. Factors such as tumor location in the upper/mid/lower pole of the kidney, tumor location in the anterior versus posterior renal cortex, location in the medial or lateral rim, and presence of exophytic versus endophytic tumor may impact the decision to perform partial nephrectomy.

Staging of Renal Cell Carcinoma. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: [email protected] Staging of Renal Cell Carcinoma presence of any nodal metastases (N1) and/ or T3 tumor. Stage IV disease is the presence of any distant metastases (M1) and/or presence of T4 tumor. Curative treatment for RCC may be accomplished with surgical resection. Partial nephrectomy is the preferred treatment option for small T1 RCC, especially because it is associated with lower risk of renal failure and cardiovascular mortality compared to radical nephrectomy. However, it has been reported that incidence of complications such as postoperative bleeding and urinary leaks may be high in partial nephrectomy. Hence, urologists carefully select patients for partial nephrectomy using preoperative scoring systems, such as the Preoperative Aspects and Dimensions Used for Anatomic assessment score, Renal Nephrometry Score, and Centrality Index. Although a full description of these scoring systems is beyond the scope of this manuscript, urologists consider various factors for surgical planning including size of the tumor and the number of lesions (such as presence of multiple and/or bilateral tumors). The location of the tumor is another important criteria. Factors such as tumor location in the upper/mid/lower pole of the kidney, tumor location in the anterior versus posterior renal cortex, location in the medial or lateral rim, and presence of exophytic versus endophytic tumor may impact the decision to perform partial nephrectomy.

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acrac_69372_2

Staging of Renal Cell Carcinoma

Furthermore, tumor involvement of renal sinus and perinephric fat, involvement of renal vein and IVC, tumor extension into adjacent organs, and presence of nodal and distant metastases are critical information needed for treatment planning. Although partial nephrectomy may be the preferred curative option in many patients, active surveillance and local ablative therapies are being increasingly considered in carefully selected patients in the management of small localized T1 RCC [5]. Locally advanced T2 to T4 RCC and complex tumors not amenable for partial nephrectomy approach may benefit from radical nephrectomy. Metastatic disease at presentation varies with the patient series but typically occurs in approximately 1 in 10 patients [6,7]. The most common sites of distant metastases, in descending order, are the lungs, bone, retroperitoneal and mediastinal nodes, liver, brain, or multiple sites [8,9]. Radical nephrectomy with metastasectomy remains an option for carefully selected patients with oligo-metastases. Similarly, cytoreductive nephrectomy may be considered even in advanced stage RCC. However, many patients with advanced stage RCC present with multifocal metastatic disease, warranting a multidisciplinary approach. Better understanding of RCC tumor biology has paved the way for the development of numerous FDA-approved therapeutic options for advanced stage RCC including targeted therapy and immunotherapy. Imaging plays an important role in the staging of RCC [10]. In this document, we provide an update on the appropriate use of imaging examinations for initial staging of known RCC. Special Imaging Considerations CT urography (CTU) is an imaging study that is tailored to improve visualization of both the upper and lower urinary tracts.

Staging of Renal Cell Carcinoma. Furthermore, tumor involvement of renal sinus and perinephric fat, involvement of renal vein and IVC, tumor extension into adjacent organs, and presence of nodal and distant metastases are critical information needed for treatment planning. Although partial nephrectomy may be the preferred curative option in many patients, active surveillance and local ablative therapies are being increasingly considered in carefully selected patients in the management of small localized T1 RCC [5]. Locally advanced T2 to T4 RCC and complex tumors not amenable for partial nephrectomy approach may benefit from radical nephrectomy. Metastatic disease at presentation varies with the patient series but typically occurs in approximately 1 in 10 patients [6,7]. The most common sites of distant metastases, in descending order, are the lungs, bone, retroperitoneal and mediastinal nodes, liver, brain, or multiple sites [8,9]. Radical nephrectomy with metastasectomy remains an option for carefully selected patients with oligo-metastases. Similarly, cytoreductive nephrectomy may be considered even in advanced stage RCC. However, many patients with advanced stage RCC present with multifocal metastatic disease, warranting a multidisciplinary approach. Better understanding of RCC tumor biology has paved the way for the development of numerous FDA-approved therapeutic options for advanced stage RCC including targeted therapy and immunotherapy. Imaging plays an important role in the staging of RCC [10]. In this document, we provide an update on the appropriate use of imaging examinations for initial staging of known RCC. Special Imaging Considerations CT urography (CTU) is an imaging study that is tailored to improve visualization of both the upper and lower urinary tracts.

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acrac_69372_3

Staging of Renal Cell Carcinoma

There is variability in the specific parameters, but it usually involves unenhanced images followed by intravenous (IV) contrast-enhanced images, including nephrographic and excretory phases acquired at least 5 minutes after contrast injection. Alternatively, a split-bolus technique uses an initial loading dose of IV contrast and then obtains a combined nephrographic-excretory phase after a second IV contrast dose; some sites include arterial phase. CTU should use thin-slice acquisition. Reconstruction methods commonly include maximum intensity projection or 3-D volume rendering. For the purposes of this document, we make a distinction between CTU and CT abdomen and pelvis without and with IV contrast. CT abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts and without both the precontrast and excretory phases. MR urography (MRU) is also tailored to improve imaging of the urinary system. Unenhanced MRU relies upon heavily T2-weighted imaging of the intrinsic high signal intensity from urine for evaluation of the urinary tract. IV contrast is administered to provide additional information regarding obstruction, urothelial thickening, focal lesions, and stones. A contrast-enhanced T1-weighted series should include corticomedullary, nephrographic, and excretory phases. Thin-slice acquisition and multiplanar imaging should be obtained. For the purposes of this document, we make a distinction between MRU and MRI abdomen and pelvis without and with IV contrast. MRI abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts, without both the precontrast and excretory phases, and without heavily T2-weighted images of the urinary tract. Staging of Renal Cell Carcinoma Discussion of Procedures by Variant Variant 1: Renal cell carcinoma.

Staging of Renal Cell Carcinoma. There is variability in the specific parameters, but it usually involves unenhanced images followed by intravenous (IV) contrast-enhanced images, including nephrographic and excretory phases acquired at least 5 minutes after contrast injection. Alternatively, a split-bolus technique uses an initial loading dose of IV contrast and then obtains a combined nephrographic-excretory phase after a second IV contrast dose; some sites include arterial phase. CTU should use thin-slice acquisition. Reconstruction methods commonly include maximum intensity projection or 3-D volume rendering. For the purposes of this document, we make a distinction between CTU and CT abdomen and pelvis without and with IV contrast. CT abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts and without both the precontrast and excretory phases. MR urography (MRU) is also tailored to improve imaging of the urinary system. Unenhanced MRU relies upon heavily T2-weighted imaging of the intrinsic high signal intensity from urine for evaluation of the urinary tract. IV contrast is administered to provide additional information regarding obstruction, urothelial thickening, focal lesions, and stones. A contrast-enhanced T1-weighted series should include corticomedullary, nephrographic, and excretory phases. Thin-slice acquisition and multiplanar imaging should be obtained. For the purposes of this document, we make a distinction between MRU and MRI abdomen and pelvis without and with IV contrast. MRI abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts, without both the precontrast and excretory phases, and without heavily T2-weighted images of the urinary tract. Staging of Renal Cell Carcinoma Discussion of Procedures by Variant Variant 1: Renal cell carcinoma.

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acrac_69372_4

Staging of Renal Cell Carcinoma

No contraindication to either iodinated CT contrast or gadolinium-based MR intravenous contrast. Staging. Bone Scan Whole Body The prevalence of osseous metastases for localized RCC has been shown to be low in patients without symptoms (ie, bone pain) or without laboratory abnormalities suggestive of osseous metastases (ie, elevated serum alkaline phosphatase level) [11,12]. Furthermore, the sites commonly involved by osseous metastases, such as the thoracolumbar spine and ribs, are located in areas covered by chest and abdominal imaging. Thus, even though bone scanning can be helpful to confirm clinically or radiographically suspected metastatic disease, current guidelines from the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) do not support its routine use in the initial staging of asymptomatic RCC [5,13]. However, in patients with RCC with symptoms suspicious for bone metastases, bone scan may be useful. Bone Scan Whole Body with SPECT or SPECT/CT Area of Interest The prevalence of osseous metastases for localized RCC has been shown to be low in patients without symptoms (ie, bone pain) or without laboratory abnormalities suggestive of osseous metastases (ie, elevated serum alkaline phosphatase level) [11,12]. Furthermore, the sites commonly involved by osseous metastases, such as the thoracolumbar spine and ribs, are located in areas covered by chest and abdominal imaging. Thus, even though bone scanning can be helpful to confirm clinically or radiographically suspected metastatic disease, current guidelines do not support its routine use in the initial staging of asymptomatic RCC [5,13]. In patients with RCC with symptoms suspicious for bone metastases, bone scan may be useful.

Staging of Renal Cell Carcinoma. No contraindication to either iodinated CT contrast or gadolinium-based MR intravenous contrast. Staging. Bone Scan Whole Body The prevalence of osseous metastases for localized RCC has been shown to be low in patients without symptoms (ie, bone pain) or without laboratory abnormalities suggestive of osseous metastases (ie, elevated serum alkaline phosphatase level) [11,12]. Furthermore, the sites commonly involved by osseous metastases, such as the thoracolumbar spine and ribs, are located in areas covered by chest and abdominal imaging. Thus, even though bone scanning can be helpful to confirm clinically or radiographically suspected metastatic disease, current guidelines from the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) do not support its routine use in the initial staging of asymptomatic RCC [5,13]. However, in patients with RCC with symptoms suspicious for bone metastases, bone scan may be useful. Bone Scan Whole Body with SPECT or SPECT/CT Area of Interest The prevalence of osseous metastases for localized RCC has been shown to be low in patients without symptoms (ie, bone pain) or without laboratory abnormalities suggestive of osseous metastases (ie, elevated serum alkaline phosphatase level) [11,12]. Furthermore, the sites commonly involved by osseous metastases, such as the thoracolumbar spine and ribs, are located in areas covered by chest and abdominal imaging. Thus, even though bone scanning can be helpful to confirm clinically or radiographically suspected metastatic disease, current guidelines do not support its routine use in the initial staging of asymptomatic RCC [5,13]. In patients with RCC with symptoms suspicious for bone metastases, bone scan may be useful.

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acrac_69372_5

Staging of Renal Cell Carcinoma

If the bone scan shows areas of abnormal radiotracer uptake suspicious for osseous metastases, single-photon emission CT (SPECT) fused with CT can be used to provide detailed anatomic localization of the abnormal radiotracer uptake and further improve the characterization of the nature of the abnormality [14]. CT Abdomen Preoperative imaging of RCC provides critical information on staging and serves as a roadmap to the surgeon. Both CT and MRI are comparable in staging of the primary tumor [15,16]. CT of the abdomen with IV contrast is considered in all major guidelines as an adequate method for staging of RCC, including the guidelines from the EAU and NCCN [5,13]. Use of IV contrast helps in the diagnosis and staging of the RCC [14,15,17-27]. Acquisition of nephrographic phase images is vital and most important in the detection and characterization of RCC. Corticomedullary phase images and excretory phase images are optional and may be helpful in differentiating RCC subtypes, distinguishing RCC from urothelial tumors and in providing complementary information on the vasculature and tumor extension into pelvicalyceal system. Extension into the perinephric fat is difficult to discriminate from nonspecific perinephric stranding due to edema, vascular engorgement, or fibrosis. High-resolution CT using thin sections appears to improve detection of perinephric infiltration, although false positives are common [15,16,33]. Various authors have reported 85% to 93% sensitivity and 32% to 96% specificity for the detection of perinephric invasion on IV contrast-enhanced CT abdomen [33-35]. In a study involving 117 patients, CT abdomen was reported to have a sensitivity of 59% to 88% and a specificity of 71% to 93% in detecting stage T3a RCC [36].

Staging of Renal Cell Carcinoma. If the bone scan shows areas of abnormal radiotracer uptake suspicious for osseous metastases, single-photon emission CT (SPECT) fused with CT can be used to provide detailed anatomic localization of the abnormal radiotracer uptake and further improve the characterization of the nature of the abnormality [14]. CT Abdomen Preoperative imaging of RCC provides critical information on staging and serves as a roadmap to the surgeon. Both CT and MRI are comparable in staging of the primary tumor [15,16]. CT of the abdomen with IV contrast is considered in all major guidelines as an adequate method for staging of RCC, including the guidelines from the EAU and NCCN [5,13]. Use of IV contrast helps in the diagnosis and staging of the RCC [14,15,17-27]. Acquisition of nephrographic phase images is vital and most important in the detection and characterization of RCC. Corticomedullary phase images and excretory phase images are optional and may be helpful in differentiating RCC subtypes, distinguishing RCC from urothelial tumors and in providing complementary information on the vasculature and tumor extension into pelvicalyceal system. Extension into the perinephric fat is difficult to discriminate from nonspecific perinephric stranding due to edema, vascular engorgement, or fibrosis. High-resolution CT using thin sections appears to improve detection of perinephric infiltration, although false positives are common [15,16,33]. Various authors have reported 85% to 93% sensitivity and 32% to 96% specificity for the detection of perinephric invasion on IV contrast-enhanced CT abdomen [33-35]. In a study involving 117 patients, CT abdomen was reported to have a sensitivity of 59% to 88% and a specificity of 71% to 93% in detecting stage T3a RCC [36].

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Staging of Renal Cell Carcinoma

In particular, CT had a 71% to 88% sensitivity and 71% to 79% specificity for renal sinus fat invasion, a 68% to 83% sensitivity and a 72% to 76% specificity for perinephric fat invasion, and a 59% to 69% sensitivity and a 91% to 93% specificity for renal vein invasion [36]. In a more recent study, 96 patients with 100 pathologically proven RCC, CT was reported to have an 86% sensitivity and 88% specificity for renal sinus fat invasion and an approximately 86% sensitivity and 97% specificity for renal vein invasion [37]. However, CT only had a modest 77% sensitivity and 72% specificity for detecting perinephric fat invasion in this study, emphasizing the difficulties in differentiating nontumoral causes for perinephric soft tissue stranding, from true tumor perinephric fat invasion [37]. Staging of Renal Cell Carcinoma It has been reported that the presence of enhancing soft tissue nodule in the perinephric fat on CT may be a helpful sign for the assessment of perinephric fat invasion. Landman et al [38] reported that the presence of enhancing perinephric soft tissue nodule had an 87% accuracy in predicting perinephric fat invasion compared with the CT finding of perinephric soft tissue stranding, which only had a 56% accuracy. However, the sensitivity of enhancing perinephric soft tissue nodule in detection of perinephric fat invasion is relatively low (31%) [38]. CT has an excellent sensitivity for detecting ipsilateral adrenal involvement in RCC (T4 tumors), but the specificity varies from 76% to 95%. One study involving 229 patients with RCC reported that CT had a 100% sensitivity for ipsilateral adrenal involvement in RCC, but only a 76% specificity [39]. However, Blakely et al [40] reported a 100% sensitivity and a 94% specificity for CT in identifying adrenal involvement. Similar findings have been reported by other authors.

Staging of Renal Cell Carcinoma. In particular, CT had a 71% to 88% sensitivity and 71% to 79% specificity for renal sinus fat invasion, a 68% to 83% sensitivity and a 72% to 76% specificity for perinephric fat invasion, and a 59% to 69% sensitivity and a 91% to 93% specificity for renal vein invasion [36]. In a more recent study, 96 patients with 100 pathologically proven RCC, CT was reported to have an 86% sensitivity and 88% specificity for renal sinus fat invasion and an approximately 86% sensitivity and 97% specificity for renal vein invasion [37]. However, CT only had a modest 77% sensitivity and 72% specificity for detecting perinephric fat invasion in this study, emphasizing the difficulties in differentiating nontumoral causes for perinephric soft tissue stranding, from true tumor perinephric fat invasion [37]. Staging of Renal Cell Carcinoma It has been reported that the presence of enhancing soft tissue nodule in the perinephric fat on CT may be a helpful sign for the assessment of perinephric fat invasion. Landman et al [38] reported that the presence of enhancing perinephric soft tissue nodule had an 87% accuracy in predicting perinephric fat invasion compared with the CT finding of perinephric soft tissue stranding, which only had a 56% accuracy. However, the sensitivity of enhancing perinephric soft tissue nodule in detection of perinephric fat invasion is relatively low (31%) [38]. CT has an excellent sensitivity for detecting ipsilateral adrenal involvement in RCC (T4 tumors), but the specificity varies from 76% to 95%. One study involving 229 patients with RCC reported that CT had a 100% sensitivity for ipsilateral adrenal involvement in RCC, but only a 76% specificity [39]. However, Blakely et al [40] reported a 100% sensitivity and a 94% specificity for CT in identifying adrenal involvement. Similar findings have been reported by other authors.

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Staging of Renal Cell Carcinoma

In another study involving 579 patients, CT was reported to have a 100% negative predictive value, a 100% sensitivity, and a 95% specificity for identifying adrenal involvement [41]. Assessment of RCC nodal metastases on CT is limited [42]. This is due to the fact that CT uses size criteria for nodal metastasis (size >1 cm in short-axis), but this leads to underestimation of disease, resulting in false negatives in the presence of micrometastases in nodes <1 cm in size. Furthermore, false positives are also often seen because of presence of reactive adenopathy, with nodes >1 cm in size. CT is accurate in detecting distant metastases in the abdomen. RCC visceral metastases may occur at various organs including liver, pancreas, adrenals, and contralateral kidney. RCC metastases tend to be hypervascular, and some authors have suggested that arterial phase imaging can be useful to accurately detect the extent of distant metastases [43-46]. CT Abdomen and Pelvis Preoperative imaging of RCC provides critical information on staging and serves as a roadmap to the surgeon. Both CT and MRI are comparable in staging of the primary tumor [15,16]. Advantages of CT include rapid acquisition time that may translate to better patient compliance and high spatial resolution. Hence, it is often the most commonly used modality for this indication. CT abdomen without and with IV contrast is typically performed for charactering a renal mass as RCC and staging the tumor. Acquisition of nephrographic phase images is vital and most important in the detection and characterization of RCC. Corticomedullary phase images and excretory phase images are optional and may be helpful in differentiating RCC subtypes, distinguishing RCC from urothelial tumors and in providing complementary information on the vasculature and tumor extension into pelvicalyceal system. Perinephric tumor extension is difficult to discriminate from nonspecific perinephric stranding due to edema, vascular engorgement, or fibrosis.

Staging of Renal Cell Carcinoma. In another study involving 579 patients, CT was reported to have a 100% negative predictive value, a 100% sensitivity, and a 95% specificity for identifying adrenal involvement [41]. Assessment of RCC nodal metastases on CT is limited [42]. This is due to the fact that CT uses size criteria for nodal metastasis (size >1 cm in short-axis), but this leads to underestimation of disease, resulting in false negatives in the presence of micrometastases in nodes <1 cm in size. Furthermore, false positives are also often seen because of presence of reactive adenopathy, with nodes >1 cm in size. CT is accurate in detecting distant metastases in the abdomen. RCC visceral metastases may occur at various organs including liver, pancreas, adrenals, and contralateral kidney. RCC metastases tend to be hypervascular, and some authors have suggested that arterial phase imaging can be useful to accurately detect the extent of distant metastases [43-46]. CT Abdomen and Pelvis Preoperative imaging of RCC provides critical information on staging and serves as a roadmap to the surgeon. Both CT and MRI are comparable in staging of the primary tumor [15,16]. Advantages of CT include rapid acquisition time that may translate to better patient compliance and high spatial resolution. Hence, it is often the most commonly used modality for this indication. CT abdomen without and with IV contrast is typically performed for charactering a renal mass as RCC and staging the tumor. Acquisition of nephrographic phase images is vital and most important in the detection and characterization of RCC. Corticomedullary phase images and excretory phase images are optional and may be helpful in differentiating RCC subtypes, distinguishing RCC from urothelial tumors and in providing complementary information on the vasculature and tumor extension into pelvicalyceal system. Perinephric tumor extension is difficult to discriminate from nonspecific perinephric stranding due to edema, vascular engorgement, or fibrosis.

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Staging of Renal Cell Carcinoma

High-resolution CT using thin sections appears to improve detection of perinephric infiltration, although false positives are common [15,16,33]. Various authors have reported an 85% to 93% sensitivity and a 32% to 96% specificity for perinephric invasion [33-35]. In a study involving 117 patients, CT abdomen was reported to have a sensitivity of 59% to 88% and a specificity of 71% to 93% in detecting stage T3a RCC [36]. In particular, CT had a 71% to 88% sensitivity and a 71% to 79% specificity for sinus fat invasion, a 68% to 83% sensitivity and a 72% to 76% specificity for perinephric invasion, and a 59% to 69% sensitivity and a 91% to 93% specificity for renal vein invasion [36]. In a more recent study of 96 patients with 100 pathologically proven RCCs, CT was reported to have an 86% sensitivity and an 88% specificity for renal sinus invasion and an approximately 86% sensitivity and a 97% specificity for renal vein invasion [37]. However, CT only had a modest 77% sensitivity and 72% specificity for detecting perinephric invasion in this study, emphasizing the difficulties in differentiating nontumoral causes for perinephric soft tissue stranding from true tumor perinephric infiltration [37]. It has been reported that presence of enhancing soft tissue nodule in the perinephric fat on CT may be a helpful sign for assessment of perinephric fat invasion. Landman et al [38] reported that the presence of enhancing perinephric soft tissue nodule had an 87% accuracy in predicting perinephric fat invasion compared with the CT finding of perinephric soft tissue stranding, which only had a 56% accuracy. However, the sensitivity of enhancing perinephric soft tissue nodule in detection of perinephric invasion is relatively low (31%) [38]. Staging of Renal Cell Carcinoma CT has excellent sensitivity for detecting ipsilateral adrenal involvement in RCC (T4 tumors), but the specificity varies from 76% to 95%.

Staging of Renal Cell Carcinoma. High-resolution CT using thin sections appears to improve detection of perinephric infiltration, although false positives are common [15,16,33]. Various authors have reported an 85% to 93% sensitivity and a 32% to 96% specificity for perinephric invasion [33-35]. In a study involving 117 patients, CT abdomen was reported to have a sensitivity of 59% to 88% and a specificity of 71% to 93% in detecting stage T3a RCC [36]. In particular, CT had a 71% to 88% sensitivity and a 71% to 79% specificity for sinus fat invasion, a 68% to 83% sensitivity and a 72% to 76% specificity for perinephric invasion, and a 59% to 69% sensitivity and a 91% to 93% specificity for renal vein invasion [36]. In a more recent study of 96 patients with 100 pathologically proven RCCs, CT was reported to have an 86% sensitivity and an 88% specificity for renal sinus invasion and an approximately 86% sensitivity and a 97% specificity for renal vein invasion [37]. However, CT only had a modest 77% sensitivity and 72% specificity for detecting perinephric invasion in this study, emphasizing the difficulties in differentiating nontumoral causes for perinephric soft tissue stranding from true tumor perinephric infiltration [37]. It has been reported that presence of enhancing soft tissue nodule in the perinephric fat on CT may be a helpful sign for assessment of perinephric fat invasion. Landman et al [38] reported that the presence of enhancing perinephric soft tissue nodule had an 87% accuracy in predicting perinephric fat invasion compared with the CT finding of perinephric soft tissue stranding, which only had a 56% accuracy. However, the sensitivity of enhancing perinephric soft tissue nodule in detection of perinephric invasion is relatively low (31%) [38]. Staging of Renal Cell Carcinoma CT has excellent sensitivity for detecting ipsilateral adrenal involvement in RCC (T4 tumors), but the specificity varies from 76% to 95%.

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Staging of Renal Cell Carcinoma

One study involving 229 patients with RCC reported that CT had a 100% sensitivity for ipsilateral adrenal involvement in RCC but only a 76% specificity [39]. However, Blakely et al [40] reported a 100% sensitivity and a 94% specificity for CT in identifying adrenal involvement. Similar findings have been reported by other authors. In another study involving 579 patients, CT was reported to have a 100% negative predictive value, a 100% sensitivity, and a 95% specificity for identifying adrenal involvement [41]. Assessment of RCC nodal metastases on CT is limited [42]. This is due to the fact that CT uses size criteria for nodal metastasis (size >1 cm in short-axis), but this leads to underestimation of disease, resulting in false negatives in the presence of micrometastases in nodes <1 cm in size. Furthermore, false positives are also often seen because of the presence of reactive adenopathy, with nodes >1 cm in size. CT is fairly accurate in detecting distant metastases in the abdomen and pelvis. RCC visceral metastases may occur at various organs including liver, pancreas, adrenals, and contralateral kidney. RCC metastases tend to be hypervascular, and some authors have suggested that arterial phase imaging can be useful to accurately detect the extent of distant metastases [43-46]. Although CT of the abdomen with IV contrast is considered in all major guidelines as an adequate method for the staging of RCC, imaging of the pelvis for RCC staging is considered optional in the guidelines [5,13]. There is no relevant literature with high-quality evidence regarding the use of CT of the pelvis in the staging of RCC. Although it is likely that CT pelvis may not offer additional information in most patients with early stage RCC, pelvic imaging can be helpful in patients with more advanced RCC, in whom metastatic spread is suspected [47,48]. CT Chest Chest imaging is indicated in the staging of RCC, given that lungs are one of the most common sites of metastases in RCC [5,13].

Staging of Renal Cell Carcinoma. One study involving 229 patients with RCC reported that CT had a 100% sensitivity for ipsilateral adrenal involvement in RCC but only a 76% specificity [39]. However, Blakely et al [40] reported a 100% sensitivity and a 94% specificity for CT in identifying adrenal involvement. Similar findings have been reported by other authors. In another study involving 579 patients, CT was reported to have a 100% negative predictive value, a 100% sensitivity, and a 95% specificity for identifying adrenal involvement [41]. Assessment of RCC nodal metastases on CT is limited [42]. This is due to the fact that CT uses size criteria for nodal metastasis (size >1 cm in short-axis), but this leads to underestimation of disease, resulting in false negatives in the presence of micrometastases in nodes <1 cm in size. Furthermore, false positives are also often seen because of the presence of reactive adenopathy, with nodes >1 cm in size. CT is fairly accurate in detecting distant metastases in the abdomen and pelvis. RCC visceral metastases may occur at various organs including liver, pancreas, adrenals, and contralateral kidney. RCC metastases tend to be hypervascular, and some authors have suggested that arterial phase imaging can be useful to accurately detect the extent of distant metastases [43-46]. Although CT of the abdomen with IV contrast is considered in all major guidelines as an adequate method for the staging of RCC, imaging of the pelvis for RCC staging is considered optional in the guidelines [5,13]. There is no relevant literature with high-quality evidence regarding the use of CT of the pelvis in the staging of RCC. Although it is likely that CT pelvis may not offer additional information in most patients with early stage RCC, pelvic imaging can be helpful in patients with more advanced RCC, in whom metastatic spread is suspected [47,48]. CT Chest Chest imaging is indicated in the staging of RCC, given that lungs are one of the most common sites of metastases in RCC [5,13].

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Staging of Renal Cell Carcinoma

There is a lack of literature that have directly compared the accuracy of chest CT with chest radiography for detecting pulmonary metastases in the initial staging of RCC. However, limited data have demonstrated that CT is more sensitive than radiography for the detection of pulmonary metastases from RCC [49]. Hence, CT chest with IV contrast is recommended by the current NCCN guidelines [13]. Apart from identifying pulmonary metastases, chest CT has a high sensitivity for the detection of hilar and mediastinal nodal metastases from RCC [50]. Although it is generally accepted that CT has a high sensitivity for detecting pulmonary nodules, it should be noted that presence of small subcentimeter pulmonary nodules does not equate to pulmonary metastases. Most patients with small T1a RCCs are unlikely to have pulmonary metastases. Prior studies have reported that the risk of metastases is highly correlated with size of the tumor and is virtually nonexistent in tumors <2 cm in size, occurs <1% in tumors of 2 to 3 cm, and occurs approximately 1% to 2% for lesions 3 to 4 cm [51-53]. Hence, the presence of small subcentimeter pulmonary nodules in T1a RCCs is often likely to be a false-positive finding (ie, intrapulmonary lymph nodes and granulomas) but can lead to further unnecessary and potentially invasive investigations. CT Head Most patients with metastases to the central nervous system are symptomatic. Thus, current guidelines from the EAU and NCCN do not support routine imaging of the brain to search for metastases in asymptomatic patients in the initial staging of RCC. Brain imaging should be performed only in cases with suggestive signs or symptoms [5,13]. Recent studies indicate that up to 4% of patients with advanced, metastatic RCC may harbor asymptomatic brain metastasis [56,57]. Hence, routine brain imaging with IV contrast may be considered in patients with advanced, metastatic RCC, even if they are asymptomatic [56,57].

Staging of Renal Cell Carcinoma. There is a lack of literature that have directly compared the accuracy of chest CT with chest radiography for detecting pulmonary metastases in the initial staging of RCC. However, limited data have demonstrated that CT is more sensitive than radiography for the detection of pulmonary metastases from RCC [49]. Hence, CT chest with IV contrast is recommended by the current NCCN guidelines [13]. Apart from identifying pulmonary metastases, chest CT has a high sensitivity for the detection of hilar and mediastinal nodal metastases from RCC [50]. Although it is generally accepted that CT has a high sensitivity for detecting pulmonary nodules, it should be noted that presence of small subcentimeter pulmonary nodules does not equate to pulmonary metastases. Most patients with small T1a RCCs are unlikely to have pulmonary metastases. Prior studies have reported that the risk of metastases is highly correlated with size of the tumor and is virtually nonexistent in tumors <2 cm in size, occurs <1% in tumors of 2 to 3 cm, and occurs approximately 1% to 2% for lesions 3 to 4 cm [51-53]. Hence, the presence of small subcentimeter pulmonary nodules in T1a RCCs is often likely to be a false-positive finding (ie, intrapulmonary lymph nodes and granulomas) but can lead to further unnecessary and potentially invasive investigations. CT Head Most patients with metastases to the central nervous system are symptomatic. Thus, current guidelines from the EAU and NCCN do not support routine imaging of the brain to search for metastases in asymptomatic patients in the initial staging of RCC. Brain imaging should be performed only in cases with suggestive signs or symptoms [5,13]. Recent studies indicate that up to 4% of patients with advanced, metastatic RCC may harbor asymptomatic brain metastasis [56,57]. Hence, routine brain imaging with IV contrast may be considered in patients with advanced, metastatic RCC, even if they are asymptomatic [56,57].

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Staging of Renal Cell Carcinoma

Staging of Renal Cell Carcinoma CTU There is no relevant literature suggesting that CTU offers any additional benefit over conventional CT of the abdomen in the initial staging of RCC, and thus, this method is not included in the guidelines from the EAU and NCCN [5,13]. FDG-PET/CT Skull Base to Mid-Thigh Fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT has a limited role in the diagnosis and local staging of RCC [58]. Differentiating renal tumor from background normal renal tissue can be difficult because of the renal excretion of FDG. Furthermore, RCC is reported to have variable FDG avidity, limiting its utility. Nakanishi et al [59] reported a 56% sensitivity, a 67% specificity, a 15% positive predictive value, a 57% negative predictive value, and a 65% accuracy for FDG-PET in the staging of RCC. A recent clinical trial from Turkey involving 62 patients with RCC reported an 84% accuracy for contrast-enhanced FDG-PET/CT in staging RCC [60]. However, further studies are warranted before PET/CT can be used in the routine initial staging of RCC. At present, given the paucity of literature to support the use of FDG-PET/CT, the guidelines from the EAU and NCCN do not recommend routine FDG-PET/CT in the initial staging of RCC [5,13]. Fluoride PET/CT Skull Base to Mid-Thigh Preliminary results for other PET tracers are also becoming available. In a small prospective study of 10 patients with metastatic RCC, 18F-sodium fluoride (NaF) PET/CT was found to be significantly more sensitive for the detection of RCC skeletal metastases than Tc-99m bone scintigraphy or CT, with sensitivities of 100%, 29%, and 46%, respectively. CT and Tc-99m bone scintigraphy in this study identified only 65% of the metastases detected by fluoride PET/CT [61].

Staging of Renal Cell Carcinoma. Staging of Renal Cell Carcinoma CTU There is no relevant literature suggesting that CTU offers any additional benefit over conventional CT of the abdomen in the initial staging of RCC, and thus, this method is not included in the guidelines from the EAU and NCCN [5,13]. FDG-PET/CT Skull Base to Mid-Thigh Fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT has a limited role in the diagnosis and local staging of RCC [58]. Differentiating renal tumor from background normal renal tissue can be difficult because of the renal excretion of FDG. Furthermore, RCC is reported to have variable FDG avidity, limiting its utility. Nakanishi et al [59] reported a 56% sensitivity, a 67% specificity, a 15% positive predictive value, a 57% negative predictive value, and a 65% accuracy for FDG-PET in the staging of RCC. A recent clinical trial from Turkey involving 62 patients with RCC reported an 84% accuracy for contrast-enhanced FDG-PET/CT in staging RCC [60]. However, further studies are warranted before PET/CT can be used in the routine initial staging of RCC. At present, given the paucity of literature to support the use of FDG-PET/CT, the guidelines from the EAU and NCCN do not recommend routine FDG-PET/CT in the initial staging of RCC [5,13]. Fluoride PET/CT Skull Base to Mid-Thigh Preliminary results for other PET tracers are also becoming available. In a small prospective study of 10 patients with metastatic RCC, 18F-sodium fluoride (NaF) PET/CT was found to be significantly more sensitive for the detection of RCC skeletal metastases than Tc-99m bone scintigraphy or CT, with sensitivities of 100%, 29%, and 46%, respectively. CT and Tc-99m bone scintigraphy in this study identified only 65% of the metastases detected by fluoride PET/CT [61].

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