IP Library Granted Patent US 11,954,596
Granted Patent B2
US 11,954,596 · App. 17/605,224 · Granted Apr 9, 2024

Weakly supervised learning with whole slide images

Inventors: Bing Song (La Canada, CA); Mustafa Jaber (Los Angeles, CA); Liudmila Beziaeva (Culver City, CA); Shahrooz Rabizadeh (Los Angeles, CA)
Assignees: NantOmics, LLC; NantHealth, Inc.
G06N3/08G06T7/0014G06T7/194G06V10/764G06V10/766G06V10/7715G06V10/774G06V10/7747G06V10/82G06V20/695G06V20/698G16H10/40G16H30/40G06T2207/10024G06T2207/20021G06T2207/20081G06T2207/20084G06T2207/30096
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Quick Facts
Patent No.
US 11,954,596
App. No.
17/605,224
Granted
Apr 9, 2024
Kind
B2
Abstract

Techniques are provided for determining classifications based on WSIs. A varied-size feature map is generated for each training WSI by generating a grid of patches for the training WSI, segmenting the training WSI into tissue and non-tissue areas, and converting patches comprising the tissue areas into tensors. Bounding boxes are generated based on the patches comprising tissue areas and segmented into feature map patches. A fixed-size feature map is generated based on a subset of the feature map patches. A classifier model is trained to process fixed-size feature maps corresponding to the training WSIs such that, for each fixed-size feature map, the classifier model is operable to assign a WSI-level tissue or cell morphology classification or regression based on the tensors. A classification engine is configured to use the trained classifier model to determine a WSI-level tissue or cell morphology classification or regression for a test WSI.

Claims (72)

1. A computerized method of determining classifications based on whole slide images (WSIs), comprising:

obtaining a plurality of training WSIs;

generating a varied-size feature map for each of the plurality of training WSIs by generating a grid of patches for the training WSI, segmenting the training WSI into tissue and non-tissue areas, and converting patches comprising the tissue areas into tensors;

generating at least one bounding box based on the patches comprising the tissue areas;

segmenting the at least one bounding box into feature map patches;

generating a fixed-size feature map based on at least a subset of the feature map patches;

configuring a classifier model to process fixed-size feature maps corresponding to the training WSIs such that, for each fixed-size feature map, the classifier model is operable to assign a WSI-level tissue or cell morphology classification or regression based on the tensors;

training the classifier model using the fixed-size feature map corresponding to the plurality of training WSIs; and

configuring a classification engine to use the trained classifier model to determine a WSI-level tissue or cell morphology classification or regression for a test WSI.

2. The method of claim 1 , wherein the plurality of training WSIs comprises less than 1000 pathology slide images.

3. The method of claim 1 , wherein the plurality of training WSIs comprises hematoxylin and eosin (H&E)-stained whole slide images.

4. The method of claim 1 , wherein each of the plurality of training WSIs corresponds to an WSI-level label indicating a classification comprising at least one of a type of cancer and a cancer grade.

5. The method of claim 1 , wherein each of the plurality of training WSIs corresponds to an WSI-level label indicating a regression comprising at least one of a percentage of tumor-infiltrating lymphocytes, RNA expression, mutation burden, and allele frequency.

6. The method of claim 1 , further comprising converting patches of the grid of patches determined to comprise non-tissue areas into tensors comprising white feature components.

7. The method of claim 1 , further comprising:

filtering the grid of patches for a minimum color variance; and

eliminating each patch determined to be empty space or background from further processing based on the filtering.

8. The method of claim 1 , wherein each of the tensors comprises a multidimensional descriptive vector.

9. The method of claim 8 , wherein the multidimensional descriptive vector comprises an RGB component.

10. The method of claim 1 , further comprising converting the RGB component into a feature vector.

11. The method of claim 10 , wherein the feature vector is a 512-feature vector for a resnet34 deep-learning neural network.

12. The method of claim 1 , wherein each of the feature map patches comprises a fixed-size patch.

13. The method of claim 1 , wherein the feature map patches comprise one of (16, 16, N) or (32, 32, N) tensors, and wherein N is a feature vector size.

14. The method of claim 1 , further comprising generating the fixed-size feature map based on a randomly selected subset of the feature map patches.

15. The method of claim 1 , wherein the subset of the feature map patches is arranged randomly within the fixed-size feature map.

16. The method of claim 1 , further comprising selecting the subset of the feature map patches for further processing.

17. The method of claim 16 , wherein the subset of the feature map patches is randomly selected to define cancer-enriched areas.

18. The method of claim 16 , wherein the subset of the feature map patches is selected to summarize tumor content within a training WSI.

19. The method of claim 1 , wherein the fixed-size feature map comprises one of a (256, 256, N) or (224, 224, N) feature map.

20. The method of claim 1 , wherein the classifier model comprises a modified resnet34 deep-learning neural network.

21. The method of claim 1 , wherein the classifier model comprises a two-layer convolutional deep-learning neural network.

22. The method of claim 1 , wherein the classifier model comprises at least one of an Inception-v3, resnet34, resnet152, densenet169, densenet201 or other deep-learning neural network.

23. The method of claim 1 , wherein each of the plurality of training WSIs corresponds to a different patient.

24. The method of claim 1 , further comprising:

obtaining the test WSI;

generating a varied-size feature map for the test WSIs by generating a grid of patches for the test WSI, segmenting the test WSI into tissue and non-tissue areas, and converting patches comprising the tissue areas into tensors;

generating at least one bounding box based on the patches comprising the tissue areas;

segmenting the at least one bounding box into feature map patches;

generating a fixed-size feature map based on at least a subset of the feature map patches; and

processing the fixed-size feature map using the trained classifier model, wherein the trained classifier model is operable to determine a WSI-level tissue or cell morphology classification or regression for the test WSI based on the fixed-size feature map.

25. An apparatus for determining classifications based on whole slide images (WSIs), the apparatus comprising:

a processor;

a memory device storing software instructions for determining molecular subtype classifications; and

a training engine executable on the processor according to software instructions stored in the memory device and configured to:

obtain a plurality of training WSIs;

generate a varied-size feature map for each of the plurality of training WSIs by generating a grid of patches for the training WSI, segmenting the training WSI into tissue and non-tissue areas, and converting patches comprising the tissue areas into tensors;

generate at least one bounding box based on the patches comprising the tissue areas;

segment the at least one bounding box into feature map patches;

generate a fixed-size feature map based on at least a subset of the feature map patches;

configure a classifier model to process fixed-size feature maps corresponding to the training WSIs such that, for each fixed-size feature map, the classifier model is operable to assign a WSI-level tissue or cell morphology classification or regression based on the tensors;

train the classifier model using the fixed-size feature map corresponding to the plurality of training WSIs; and

configure a classification engine to use the trained classifier model to determine a WSI-level tissue or cell morphology classification or regression for a test WSI.

26. A non-transitory computer-readable medium having computer instructions stored thereon for determining classifications based on whole slide images (WSIs), which, when executed by a processor, cause the processor to perform one or more steps comprising:

obtaining a plurality of training WSIs;

generating a varied-size feature map for each of the plurality of training WSIs by generating a grid of patches for the training WSI, segmenting the training WSI into tissue and non-tissue areas, and converting patches comprising the tissue areas into tensors;

generating at least one bounding box based on the patches comprising the tissue areas;

segmenting the at least one bounding box into feature map patches;

generating a fixed-size feature map based on at least a subset of the feature map patches;

configuring a classifier model to process fixed-size feature maps corresponding to the training WSIs such that, for each fixed-size feature map, the classifier model is operable to assign a WSI-level tissue or cell morphology classification or regression based on the tensors;

training the classifier model using the fixed-size feature map corresponding to the plurality of training WSIs; and

configuring a classification engine to use the trained classifier model to determine a WSI-level tissue or cell morphology classification or regression for a test WSI.

27. An apparatus for determining classifications based on whole slide images (WSIs), the apparatus comprising:

a processor;

a memory device storing software instructions for determining tissue or cell morphology classifications or regressions; and

a classification engine executable on the processor according to software instructions stored in the memory device and configured to:

obtain a test WSI;

generate a varied-size feature map for the test WSI by generating a grid of patches for the test WSI, segmenting the test WSI into tissue and non-tissue areas, and converting patches comprising the tissue areas into tensors;

generate at least one bounding box based on the patches comprising the tissue areas;

segment the at least one bounding box into feature map patches;

generate a fixed-size feature map based on at least a subset of the feature map patches; and

determine a WSI-level tissue or cell morphology classification or regression for the test WSI using a classifier model trained to process the fixed-size feature map such that a WSI-level tissue or cell morphology classification or regression is determined based on the fixed-size feature map.

28. The apparatus of claim 27 , wherein the classification engine comprises at least one of a cellular smartphone, kiosk, personal data assistant, tablet, robot, vehicle, web camera, or computing device.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 28, 2021
From: SONG, BING
To: NANTOMICS, LLC
Reel/Frame 057955/0594 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 28, 2021
From: BEZIAEVA, LIUDMILA A.
To: NANTHEALTH, INC.
Reel/Frame 057955/0602 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 28, 2021
From: JABER, MUSTAFA
To: NANTOMICS, LLC
Reel/Frame 057955/0622 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 28, 2021
From: RABIZADEH, SHAHROOZ
To: NANTOMICS, LLC
Reel/Frame 057955/0651 →
Continuity (2)
Provisional Application 62838839 · Apr 25, 2019
Related Publication 20220180626A1 · Jun 9, 2022
Cited By (3)
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