File size: 9,090 Bytes
12d2e9e
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
"""
Copyright 2021, Dana-Farber Cancer Institute and Weill Cornell Medicine
License: GNU GPL 2.0
"""

import math

import numpy as np
import torch
from skimage.measure import label, regionprops
from torch_geometric.data import Data
from torch_geometric.utils import remove_self_loops, to_edge_index, to_torch_csr_tensor

MIN_NR_PIXELS = 50000
MAX_NR_PIXELS = 50000000


class Graph(Data):
    """Constructs pytorch-geometric data object for saving and loading

    Args:
        node_centroids (torch.tensor): Coordinates of the centers of each entity (cell or tissue) in the graph
        node_features (torch.tensor): Computed features of each entity (cell or tissue) in the graph
        edge_index (torch.tensor): Edge index in sparse format between nodes in the graph
        node_labels  (torch.tensor): Node labels of each entity (cell or tissue) in the graph. Defaults to None.
        target (torch.tensor): Target label if used in a supervised setting. Defaults to None.
    """

    def __init__(
        self,
        node_centroids,
        edge_index,
        node_features=None,
        node_labels=None,
        edge_features=None,
        target=None,
    ):
        super().__init__()
        self.node_centroids = node_centroids
        self.node_features = node_features
        self.edge_index = edge_index
        self.node_labels = node_labels
        self.target = target
        self.edge_features = edge_features

    def __inc__(self, key, value, *args, **kwargs):
        if key == "edge_index":
            return self.node_centroids.size(0)
        elif key == "target":
            return 0
        else:
            return super().__inc__(key, value, *args, **kwargs)


class HACTPairData(Data):
    """Constructs pytorch-geometric data object for handling both cell and tissue data.

    Args:
        x_cell (torch.tensor): Computed features of each cell in the graph
        edge_index_cell (torch.tensor): Edge index in sparse format between nodes in the cell graph
        x_tissue (torch.tensor): Computed features of each tissue in the graph
        edge_index_tissue (torch.tensor): Edge index in sparse format between nodes in the tissue graph
        assignment (torch.tensor): Assigment matrix that contains mapping between cells and tissues.
        target (torch.tensor): Target label if used in a supervised setting.

    References:
        Jaume, G., Pati, P., Anklin, V., Foncubierta, A. and Gabrani, M., 2021, September.
        Histocartography: A toolkit for graph analytics in digital pathology.
        In MICCAI Workshop on Computational Pathology (pp. 117-128). PMLR.
    """

    def __init__(
        self, x_cell, edge_index_cell, x_tissue, edge_index_tissue, assignment, target
    ):
        super().__init__()
        self.x_cell = x_cell
        self.edge_index_cell = edge_index_cell

        self.x_tissue = x_tissue
        self.edge_index_tissue = edge_index_tissue

        self.assignment = assignment
        self.target = target

    def __inc__(self, key, value, *args, **kwargs):
        if key == "edge_index_cell":
            return self.x_cell.size(0)
        if key == "edge_index_tissue":
            return self.x_tissue.size(0)
        elif key == "assignment":
            return self.x_tissue.size(0)
        elif key == "target":
            return 0
        else:
            return super().__inc__(key, value, *args, **kwargs)


def get_full_instance_map(wsi, patch_size, mask_name="cell"):
    """
    Generates and returns the normalized image, cell instance map and cell centroids from pathml SlideData object

    Args:
        wsi (pathml.core.SlideData): Normalized WSI object with detected cells in the 'masks' slot
        patch_size (int): Patch size used for cell detection
        mask_name (str): Name of the mask slot storing the detected cells. Defaults to 'cell'.

    Returns:
        The image in np.unint8 format, the instance map for the entity and the instance centroids for each entity in
        the instance map as numpy arrays.
    """

    x = math.ceil(wsi.shape[0] / patch_size) * patch_size
    y = math.ceil(wsi.shape[1] / patch_size) * patch_size
    image_norm = np.zeros((x, y, 3))
    instance_map = np.zeros((x, y))
    for tile in wsi.tiles:
        tx, ty = tile.coords
        image_norm[tx : tx + patch_size, ty : ty + patch_size] = tile.image
        instance_map[tx : tx + patch_size, ty : ty + patch_size] = np.squeeze(
            tile.masks[mask_name]
        )[:, :]
    image_norm = image_norm[: wsi.shape[0], : wsi.shape[1], :]
    instance_map = instance_map[: wsi.shape[0], : wsi.shape[1]]
    label_instance_map = label(instance_map)
    regions = regionprops(label_instance_map)
    instance_centroids = np.empty((len(regions), 2))
    for i, region in enumerate(regions):
        center_y, center_x = region.centroid  # row, col
        center_x = int(round(center_x))
        center_y = int(round(center_y))
        instance_centroids[i, 0] = center_x
        instance_centroids[i, 1] = center_y
    return image_norm.astype("uint8"), label_instance_map, instance_centroids


def build_assignment_matrix(low_level_centroids, high_level_map, matrix=False):
    """
    Builds an assignment matrix/mapping between low-level centroid locations and a high-level segmentation map

    Args:
        low_level_centroids (numpy.array): The low-level centroid coordinates in x-y plane
        high-level map (numpy.array): The high-level map returned from regionprops
        matrix (bool): Whether to return in a matrix format. If True, returns a N*L matrix where N is the number of low-level
            instances and L is the number of high-level instances. If False, returns this mapping in sparse format.
            Defaults to False.

    Returns:
        The assignment matrix as a numpy array.

    References:
        [1] https://github.com/BiomedSciAI/histocartography/tree/main
        [2] Jaume, G., Pati, P., Anklin, V., Foncubierta, A. and Gabrani, M., 2021, September.
        Histocartography: A toolkit for graph analytics in digital pathology.
        In MICCAI Workshop on Computational Pathology (pp. 117-128). PMLR.
    """

    low_level_centroids = low_level_centroids.astype(int)
    low_to_high = high_level_map[
        low_level_centroids[:, 1], low_level_centroids[:, 0]
    ].astype(int)
    high_instance_ids = np.sort(np.unique(np.ravel(high_level_map))).astype(int)
    if 0 in high_instance_ids:
        high_instance_ids = np.delete(high_instance_ids, 0)
    assignment_matrix = np.zeros((low_level_centroids.shape[0], len(high_instance_ids)))
    assignment_matrix[np.arange(low_to_high.size), low_to_high - 1] = 1
    if not matrix:
        sparse_matrix = np.nonzero(assignment_matrix)
        return np.array(sparse_matrix)
    return assignment_matrix


def two_hop(edge_index, num_nodes):
    """Calculates the two-hop graph.
    Args:
        edge_index (torch.tensor): The edge index in sparse form of the graph.
        num_nodes (int): maximum number of nodes.

    Returns:
        torch.tensor: Output edge index tensor.

    References:
        [1] https://github.com/BiomedSciAI/histocartography/tree/main
        [2] Jaume, G., Pati, P., Anklin, V., Foncubierta, A. and Gabrani, M., 2021, September.
        Histocartography: A toolkit for graph analytics in digital pathology.
        In MICCAI Workshop on Computational Pathology (pp. 117-128). PMLR.
    """
    adj = to_torch_csr_tensor(edge_index, size=(num_nodes, num_nodes))
    try:
        edge_index2, _ = to_edge_index(adj @ adj)
        edge_index2, _ = remove_self_loops(edge_index2)
        edge_index = torch.cat([edge_index, edge_index2], dim=1)
    except RuntimeError as e:  # pragma: no cover
        print(e, "Computing two-hop graph manually")
        edge_index = two_hop_no_sparse(edge_index, num_nodes)
    return edge_index


def two_hop_no_sparse(edge_index, num_nodes):  # pragma: no cover
    """Calculates the two-hop graph without using sparse tensors, in case of M1/M2 chips.
    Args:
        edge_index (torch.tensor): The edge index in sparse form of the graph (2, E)
        num_nodes (int): maximum number of nodes.
    Returns:
        torch.tensor: Output edge index tensor.
    """
    # Initialize an empty list to store the two-hop edges
    two_hop_edges = []

    # Convert edge_index tensor to a list of tuples (edges)
    edges = edge_index.t().tolist()

    # Iterate over all pairs of nodes
    for src, dest in edges:
        # First hop: Add direct edges
        two_hop_edges.append([src, dest])

        # Second hop: Find all neighbors of the destination node
        for neighbor in range(num_nodes):
            # Check if the neighbor is connected to the destination node
            if [dest, neighbor] in edges:
                # Avoid self-loops
                if neighbor != src:
                    two_hop_edges.append([src, neighbor])

    # Convert the list of two-hop edges to a PyTorch tensor
    edge_index_two_hop = torch.tensor(two_hop_edges).t().contiguous()

    return edge_index_two_hop