IP Library Granted Patent US 9,031,306
Granted Patent B2
US 9,031,306 · App. 13/886,213 · Granted May 12, 2015

Diagnostic and prognostic histopathology system using morphometric indices

Inventors: Bahram Parvin (Mill Valley, CA); Hang Chang (Moraga, CA); Ju Han (Albany, CA); Gerald V. Fontenay (San Francisco, CA)
Assignee: The Regents of the University of California
A61B5/0033A61B5/7275G06T7/0014G06T2207/20076G06T2207/30024G06T2207/30096
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Quick Facts
Patent No.
US 9,031,306
App. No.
13/886,213
Granted
May 12, 2015
Kind
B2
Abstract

Determining at least one of a prognosis or a therapy for a patient based on a stained tissue section of the patient. An image of a stained tissue section of a patient is processed by a processing device. A set of features values for a set of cell-based features is extracted from the processed image, and the processed image is associated with a particular cluster of a plurality of clusters based on the set of feature values, where the plurality of clusters is defined with respect to a feature space corresponding to the set of features.

Claims (38)

1. A method comprising:

processing, by a processing device, an image of a stained tissue section of a patient;

extracting from the processed image a set of feature values for a set of cell-based features;

associating, based on the set of feature values, the processed image with a particular cluster of a plurality of clusters, wherein the plurality of clusters is defined with respect to a feature space corresponding to the set of features, wherein the particular cluster identifies a morphometric subtype; and

determining whether the morphometric subtype is prognostic-predictive and, in response:

characterizing heterogeneity of a tumor of the patient and evaluating whether heterogeneity is more virulent in terms of prognosis or prediction, and

inferring molecular correlates of a compute morphometric subtype through association with genome-wide molecular data for the tumor.

2. The method of claim 1 wherein the processing of the image comprises normalizing the image in a color map space with respect to a plurality of reference images, and wherein the method further comprises determining at least one of a prognosis or a therapy for the patient based on the particular cluster and historical data associated with the particular cluster.

3. The method of claim 2 wherein the reference images are represented in the feature space as a Gaussian Mixture Model.

4. The method of claim 1 wherein the processing of the image comprises using an image-based model to remove technical variation and biological hetereogeneity.

5. The method of claim 1 wherein the processing of the image comprises applying a graph cut to the subimage to identify nuclei.

6. The method of claim 1 further comprising administering the therapy.

7. The method of claim 1 wherein the processing of the image comprises applying one or more geometric constraints to infer edges between nuclei.

8. A non-transitory computer readable storage medium including instructions that, when executed by a processing device, cause the processing device to perform operations comprising:

determining, by the processing device and based on historical data, whether a morphometric subtype of a set of histology sections is prognostic-predictive; and

in response to determining that the morphometric subtype is prognostic-predictive:

determining, by the processing device and based on the historical data, at least one of a prognosis or a therapy for the morphometric subtype, and

populating, by the processing device, a database with a record that associates the morphometric subtype with the at least one of the prognosis or the therapy.

9. The non-transitory computer readable storage medium of claim 8 wherein the morphometric subtype is determined via clustering of a plurality of feature sets in a feature space, and wherein each of the plurality of feature sets is obtained by processing an image of a respective set of histology sections.

10. The non-transitory computer readable storage medium of claim 9 wherein the processing of the image comprises normalizing the image in a color map space with respect to a plurality of reference images.

11. The non-transitory computer readable storage medium of claim 9 wherein the processing of the image comprises representing the image in the feature space as a Gaussian Mixture Model.

12. The non-transitory computer readable storage medium of claim 9 , further comprising in response to determining that the morphometric subtype is prognostic-predictive:

characterizing tumor heterogeneity and evaluating whether heterogeneity is more virulent in terms of prognosis or prediction, and

inferring molecular correlates of a compute morphometric subtype through association with genome-wide molecular data for a tumor.

13. The non-transitory computer readable storage medium of claim 9 wherein the processing of the image comprises applying a graph cut to the subimage to identify nuclei.

14. The non-transitory computer readable storage medium of claim 9 wherein the processing of the image comprises detecting points of maximum curvature along a contour of a nuclear mask and triangulating the points of maximum curvature.

15. The non-transitory computer readable storage medium of claim 9 wherein the processing of the image comprises applying one or more geometric constraints to infer edges between nuclei.

16. A system comprising:

a memory to store an image of a stained tissue section of a patient; and

a processing device operatively coupled with the memory, the processing device to:

process the image,

extract from the processed image a set of feature values for a set of cell-based features,

associate, based on the set of feature values, the processed image with a particular cluster of a plurality of clusters, wherein the plurality of clusters is defined with respect to a feature space corresponding to the set of features, and

determine a quantification of a tumor property that identifies an intrinsic subtype.

17. The system of claim 16 wherein to process the subimage, the processing device is to normalize the subimage in a color map space with respect to a plurality of reference images.

18. The system of claim 16 wherein the set of cell-based features comprises average nucleus size.

19. The system of claim 16 wherein to process the subimage, the processing device is to apply at least one of a local fitness term or a global fitness term.

20. The system of claim 16 wherein to process the subimage, the processing device is to apply a graph cut to the subimage to identify nuclei.

Assignments (2)
CONFIRMATORY LICENSE Recorded Nov 1, 2013
From: REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE
To: ENERGY,UNITED STATES DEPARTMENT OF
Reel/Frame 031610/0953 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 21, 2013
From: PARVIN, BAHRAM; CHANG, HANG; HAN, JU; FONTENAY, GERALD V.
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 030664/0815 →
Continuity (2)
Provisional Application 61641798 · May 2, 2012
Related Publication 20130294676A1 · Nov 7, 2013