IP Library › Granted Patent US 12,469,128
Granted Patent B2
US 12,469,128 · App. 17/862,973 · Granted Nov 11, 2025

Non-tumor segmentation to support tumor detection and analysis

Inventors: Auranuch Lorsakul (Tucson, AZ); Kien Nguyen (Tucson, AZ); Zuo Zhao (Tucson, AZ)
Assignee: VENTANA MEDICAL SYSTEMS, INC.
G06T7/0012G06T7/11G06T2207/20084G06T2207/30024
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,469,128
App. No.
17/862,973
Granted
Nov 11, 2025
Kind
B2
Abstract

The present disclosure relates machine learning techniques for segmenting non-tumor regions in specimen images to support tumor detection and analysis. Particularly, aspects of the present disclosure are directed to accessing one or more images that comprise a non-target region (e.g., a non-tumor region) and a target region (e.g., a tumor region), predicting, by a two-dimensional segmentation model, segmentation maps for the non-target region based on discriminative features encoded from the one or more images, a segmentation mask for the one or more images based on the segmentation maps, applying the segmentation mask to the one or more images to generate non-target region masked images that exclude the non-target region from the one or more images, and classifying, by an image analysis model, a biological material or structure within the target region based on a set of features extracted from the non-target region masked images.

Claims (47)

1 . A computer-implemented method comprising:

accessing a plurality of images for a specimen, wherein one or more images of the plurality of images comprise a non-target region and a target region;

splitting the one or more images into image patches having a predetermined size;

encoding, by a two-dimensional segmentation model, the image patches into discriminative features;

projecting, by the two-dimensional segmentation model, the discriminative features onto a pixel space;

determining, by the two-dimensional segmentation model, a classification of a first biological material or structure for each pixel space based on a predetermined threshold;

predicting, by the two-dimensional segmentation model, segmentation maps for the non-target region based on the discriminative features, wherein the discriminative features are associated with the first biological material or structure;

generating a segmentation mask for the one or more images based on the segmentation maps;

applying the segmentation mask to the one or more images to generate non-target region masked images that exclude the non-target region from the one or more images;

classifying, by an image analysis model, a second biological material or structure within the target region as a type of cell or cell nuclei based on a set of features extracted from the non-target region masked images; and

providing, for the target region, the type of cell or cell nuclei classified for the second biological material or structure.

2 . The computer-implemented method of claim 1 , wherein the specimen is stained for one or more biomarkers, the first biological material or structure is a lymphoid aggregate, and the second biological material or structure is a tumor cell or cluster of tumor cells.

3 . The computer-implemented method of claim 1 , further comprising:

extracting, by the image analysis model, the set of features from the non-target region masked images; and

computing one or more metrics for the second biological material or structure based on the set of features,

wherein the providing the type of cell or cell nuclei classified for the second biological material or structure further comprises providing the one or more metrics for the second biological material or structure.

4 . The computer-implemented method of claim 1 , wherein the two-dimensional segmentation model is a modified U-Net model comprising a contracting path and an expansive path, each of the contracting path and the expansive path having a maximum of 256 channels, and one or more layers of the contracting path implement spatial drop out.

5 . The computer-implemented method of claim 4 , wherein the contracting path is configured to encode the image patches into discriminative features.

6 . The computer-implemented method of claim 5 , wherein the contracting path is configured to encode the image patches into discriminative features at multiple different levels.

7 . The computer-implemented method of claim 4 , wherein the expansive path is configured to project the discriminative features onto the pixel space.

8 . The computer-implemented method of claim 7 , wherein the expansive path is configured to project the discriminative features onto the pixel space at multiple different levels.

9 . The computer-implemented method of claim 1 , wherein the first biological material or structure is associated with the non-target region.

10 . The computer-implemented method of claim 1 , wherein the predetermined threshold is a hyperparameter that is optimized during training of the two-dimensional segmentation model.

11 . A computer-implemented method comprising:

accessing a plurality of images for a specimen, wherein one or more images of the plurality of images comprise a non-target region and a target region;

splitting the one or more images into image patches having a predetermined size;

encoding, by a two-dimensional segmentation model, the image patches into discriminative features;

projecting, by the two-dimensional segmentation model, the discriminative features onto a pixel space;

determining, by the two-dimensional segmentation model, a classification of a first biological material or structure for each pixel space based on a predetermined threshold;

predicting, by the two-dimensional segmentation model, segmentation maps for the non-target region based on the discriminative features, wherein the discriminative features are associated with the first biological material or structure;

generating a first segmentation mask for the one or more images based on the segmentation maps for the non-target region;

classifying, by an image analysis model, a second biological material or structure within the target region as a type of cell or cell nuclei based on a second set of features extracted from the one or more images;

generating a second segmentation mask for the one or more images based on the classification of the second biological material or structure within the target region;

applying the first segmentation mask and the second segmentation mask to the one or more images to generate target region and non-target region masked images that exclude the non-target region from the one or more images; and

providing the target region and non-target region masked images and the type of cell or cell nuclei classified for the second biological material or structure.

12 . The computer-implemented method of claim 11 , wherein the specimen is stained for one or more biomarkers, the first biological material or structure is a lymphoid aggregate, and the second biological material or structure is a tumor cell or cluster of tumor cells.

13 . The computer-implemented method of claim 11 , further comprising:

extracting, by the image analysis model, the second set of features from the one or more images; and

computing one or more metrics for the second biological material or structure based on the second set of features,

wherein the providing the target region and non-target region masked images and the type of cell or cell nuclei classified for the second biological material or structure further comprises providing the one or more metrics for the second biological material or structure.

14 . The computer-implemented method of claim 11 , wherein the two-dimensional segmentation model is a modified U-Net model comprising a contracting path and an expansive path, each of the contracting path and the expansive path having a maximum of 256 channels, and one or more layers of the contracting path implement spatial drop out.

15 . The computer-implemented method of claim 14 , wherein the contracting path is configured to encode the image patches into discriminative features.

16 . The computer-implemented method of claim 15 , wherein the contracting path is configured to encode the image patches into discriminative features at multiple different levels.

17 . The computer-implemented method of claim 14 , wherein the expansive path is configured to project the discriminative features onto the pixel space.

18 . The computer-implemented method of claim 17 , wherein the expansive path is configured to project the discriminative features onto the pixel space at multiple different levels.

19 . The computer-implemented method of claim 11 , wherein the first biological material or structure is associated with the non-target region.

20 . The computer-implemented method of claim 11 , wherein the predetermined threshold is a hyperparameter that is optimized during training of the two-dimensional segmentation model.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2024
From: LORSAKUL, AURANUCH; NGUYEN, KIEN; ZHAO, ZUO
To: VENTANA MEDICAL SYSTEMS, INC.
Reel/Frame 066096/0866 →
Continuity (3)
Continuation PCTUS2021013947 · Jan 19, 2021
Provisional Application 62963145 · Jan 19, 2020
Related Publication 20220351379A1 · Nov 3, 2022
References Cited (31)
US 7760927B2 · Gholap et al. · 2010 [cited by applicant]
US 20060083418A1 · Watson · 2006 [cited by examiner]
US 20170103521A1 · Chukka et al. · 2017 [cited by applicant]
US 20170140246A1 · Barnes et al. · 2017 [cited by applicant]
US 20190392578A1 · Chukka · 2019 [cited by examiner]
CN 110088804A · 2019 [cited by applicant]
CN 110675411A · 2020 [cited by examiner]
JP 2006517663A · 2006 [cited by applicant]
JP 2020502534A · 2020 [cited by applicant]
WO 2014102130A1 · 2014 [cited by applicant]
WO 2014140085A1 · 2014 [cited by applicant]
WO 2015049233A1 · 2015 [cited by applicant]
WO 2015181371A1 · 2015 [cited by applicant]
WO 2016120442A1 · 2016 [cited by applicant]
WO 2018115055A1 · 2018 [cited by applicant]
WO 2019110567A1 · 2019 [cited by applicant]
JP Application No. 2022-543485, “Office Action”, Mailed on Aug. 15, 2023, 12 pages. [cited by applicant]
International Application No. PCT/US2021/013947 , “International Preliminary Report on Patentability”, Mailed on Jul. 28, 2022, 15 pages. [cited by applicant]
International Application No. PCT/US2021/013947 , “International Search Report and Written Opinion”, Mailed on Apr. 30, 2021, 19 pages. [cited by applicant]
JP Application No. 2022-543485 , “Notice of Decision to Grant”, Dec. 19, 2023, 6 pages. [cited by applicant]
Caicedo et al., “Evaluation of Deep Learning Strategies for Nucleus Segmentation in Fluorescence Images”, NIH Public Access Author Manuscript. vol. 95, No. 9, Jul. 16, 2019, pp. 942-962. [cited by applicant]
Li et al., “A Multi-Scale U-Net for Semantic Segmentation of Histological Images from Radical Prostatectomies”, AMIA Annual Symposium Proceedings, 2017, pp. 1140-1148. [cited by applicant]
Long et al., “Microscopy Cell Nuclei Segmentation with Enhanced U-Net”, BMC Bioinformatics. vol. 21, No. 1, Jan. 8, 2020, 12 pages. [cited by applicant]
Oskal et al., “A U-Net Based Approach to Epidermal Tissue Segmentation in Whole Slide Histopathological Images”, SN Applied Sciences, vol. 1, No. 672, Jun. 7, 2019, 12 pages. [cited by applicant]
Su et al., “Automatic Detection of Cervical Cancer Cells by a Two-Level Cascade Classification System”, Analytical Cellular Pathology. vol. 2016, 2016, pp. 1-11. [cited by applicant]
Parvin, Bahram, et al. “Iterative voting for inference of structural saliency and characterization of subcellular events.” Image Processing, IEEE Transactions on 16.3 (2007): 615-623. [cited by applicant]
Cuzick, et al., “Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison with the Genomic Health Recurrence S… [cited by applicant]
Barton, et al., “Assessment of the Contribution of the IHC4 + C Score to Decision Making in Clinical Practice in Early Breast Cancer”, British Journal of Cancer, 2012 106, 1760-1765. [cited by applicant]
CN Application No. 202180008998.8 “Office Action”, Nov. 23, 2024, 19 pages. [cited by applicant]
CN Application No. 202180008998.8, “Office Action”, Jul. 11, 2025, 5 pages. [cited by applicant]
Ronneberger et al., “U-Net: Convolutional Networks for Biomedical Image Segmentation”, Computer Science Department and BIOSS Centre for Biological Signalling Studies, University of Freiburg, Germany Available online at:… [cited by applicant]