File size: 6,747 Bytes
287a683
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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
import os
import random

import torch
from PIL import Image
from torchstain.base.normalizers.he_normalizer import HENormalizer
from torchstain.torch.utils import cov, percentile
from torchvision import transforms
from torchvision.transforms.functional import to_pil_image


def preprocessor(pretrained=False, normalizer=None):
    if pretrained:
        mean = (0.485, 0.456, 0.406)
        std = (0.229, 0.224, 0.225)
    else:
        mean = (0.5, 0.5, 0.5)
        std = (0.5, 0.5, 0.5)

    preprocess = transforms.Compose(
        [
            transforms.Resize(256),
            transforms.CenterCrop(224),
            transforms.Lambda(lambda x: x) if normalizer == None else normalizer,
            transforms.ToTensor(),
            transforms.Normalize(mean=mean, std=std),
        ]
    )

    return preprocess


"""
Source code ported from: https://github.com/schaugf/HEnorm_python
Original implementation: https://github.com/mitkovetta/staining-normalization
"""


class TorchMacenkoNormalizer(HENormalizer):
    def __init__(self):
        super().__init__()

        self.HERef = torch.tensor(
            [[0.5626, 0.2159], [0.7201, 0.8012], [0.4062, 0.5581]]
        )
        self.maxCRef = torch.tensor([1.9705, 1.0308])

        # Avoid using deprecated torch.lstsq (since 1.9.0)
        self.updated_lstsq = hasattr(torch.linalg, "lstsq")

    def __convert_rgb2od(self, I, Io, beta):
        I = I.permute(1, 2, 0)

        # calculate optical density
        OD = -torch.log((I.reshape((-1, I.shape[-1])).float() + 1) / Io)

        # remove transparent pixels
        ODhat = OD[~torch.any(OD < beta, dim=1)]

        return OD, ODhat

    def __find_HE(self, ODhat, eigvecs, alpha):
        # project on the plane spanned by the eigenvectors corresponding to the two
        # largest eigenvalues
        That = torch.matmul(ODhat, eigvecs)
        phi = torch.atan2(That[:, 1], That[:, 0])
        # print(phi.size())

        minPhi = percentile(phi, alpha)
        maxPhi = percentile(phi, 100 - alpha)

        vMin = torch.matmul(
            eigvecs, torch.stack((torch.cos(minPhi), torch.sin(minPhi)))
        ).unsqueeze(1)
        vMax = torch.matmul(
            eigvecs, torch.stack((torch.cos(maxPhi), torch.sin(maxPhi)))
        ).unsqueeze(1)

        # a heuristic to make the vector corresponding to hematoxylin first and the
        # one corresponding to eosin second
        HE = torch.where(
            vMin[0] > vMax[0],
            torch.cat((vMin, vMax), dim=1),
            torch.cat((vMax, vMin), dim=1),
        )

        return HE

    def __find_concentration(self, OD, HE):
        # rows correspond to channels (RGB), columns to OD values
        Y = OD.T

        # determine concentrations of the individual stains
        if not self.updated_lstsq:
            return torch.lstsq(Y, HE)[0][:2]

        return torch.linalg.lstsq(HE, Y)[0]

    def __compute_matrices(self, I, Io, alpha, beta):
        OD, ODhat = self.__convert_rgb2od(I, Io=Io, beta=beta)

        # compute eigenvectors
        _, eigvecs = torch.linalg.eigh(cov(ODhat.T))
        eigvecs = eigvecs[:, [1, 2]]

        HE = self.__find_HE(ODhat, eigvecs, alpha)

        C = self.__find_concentration(OD, HE)
        maxC = torch.stack([percentile(C[0, :], 99), percentile(C[1, :], 99)])

        return HE, C, maxC

    def fit(self, I, Io=240, alpha=1, beta=0.15):
        HE, _, maxC = self.__compute_matrices(I, Io, alpha, beta)

        self.HERef = HE
        self.maxCRef = maxC

    def normalize(
        self, I, Io=240, alpha=1, beta=0.15, stains=True, form="chw", dtype="int"
    ):
        """Normalize staining appearence of H&E stained images

        Example use:
            see test.py

        Input:
            I: RGB input image: tensor of shape [C, H, W] and type uint8
            Io: (optional) transmitted light intensity
            alpha: percentile
            beta: transparency threshold
            stains: if true, return also H & E components

        Output:
            Inorm: normalized image
            H: hematoxylin image
            E: eosin image

        Reference:
            A method for normalizing histology slides for quantitative analysis. M.
            Macenko et al., ISBI 2009
        """

        c, h, w = I.shape

        HE, C, maxC = self.__compute_matrices(I, Io, alpha, beta)

        # normalize stain concentrations
        C *= (self.maxCRef / maxC).unsqueeze(-1)

        # recreate the image using reference mixing matrix
        Inorm = Io * torch.exp(-torch.matmul(self.HERef, C))
        Inorm = torch.clip(Inorm, 0, 255)

        Inorm = Inorm.reshape(c, h, w).float() / 255.0
        Inorm = torch.clip(Inorm, 0.0, 1.0)

        H, E = None, None

        if stains:
            H = torch.mul(
                Io,
                torch.exp(
                    torch.matmul(-self.HERef[:, 0].unsqueeze(-1), C[0, :].unsqueeze(0))
                ),
            )
            H[H > 255] = 255
            H = H.T.reshape(h, w, c).int()

            E = torch.mul(
                Io,
                torch.exp(
                    torch.matmul(-self.HERef[:, 1].unsqueeze(-1), C[1, :].unsqueeze(0))
                ),
            )
            E[E > 255] = 255
            E = E.T.reshape(h, w, c).int()

        return Inorm, H, E


class MacenkoNormalizer:
    def __init__(self, target_path=None, prob=1):
        self.transform_before_macenko = transforms.Compose(
            [transforms.ToTensor(), transforms.Lambda(lambda x: x * 255)]
        )
        self.normalizer = TorchMacenkoNormalizer()

        ext = os.path.splitext(target_path)[1].lower()
        if ext in [".jpg", ".jpeg", ".png"]:
            target = Image.open(target_path)
            self.normalizer.fit(self.transform_before_macenko(target))
        elif ext in [".pt"]:
            target = torch.load(target_path)
            self.normalizer.HERef = target["HERef"]
            self.normalizer.maxCRef = target["maxCRef"]

        else:
            raise ValueError(f"Invalid extension: {ext}")
        self.prob = prob

    def __call__(self, image):
        t_to_transform = self.transform_before_macenko(image)
        try:
            image_macenko, _, _ = self.normalizer.normalize(
                I=t_to_transform, stains=False, form="chw", dtype="float"
            )
            if torch.any(torch.isnan(image_macenko)):
                return image
            else:
                image_macenko = to_pil_image(image_macenko)
                return image_macenko
        except Exception as e:
            if "kthvalue()" in str(e) or "linalg.eigh" in str(e):
                pass
            else:
                print(str(e))
            return image