Automated scanning method for pathology samples

• US 20030012420A1
• Filed: 06/06/2002
• Published: 01/16/2003
• Est. Priority Date: 06/12/2001
• Status: Active Grant

• Current Assignee: Leica Biosystems Imaging Inc. (Danaher Corporation)
• Original Assignee: Applied Imaging Corporation (Danaher Corporation)
• Inventors: Shields, Kevin, Sloos, Willem C.R., OʼKelly, Padraig S., Gregson, Mark, Mesker, Wilhelmina E., Vrolijk, Johannes, Tanke, Hendrikus J., Verwoerd, Nico Peter, Bonnet, Jan
• Granted Patent: US 7,133,543 B2
• Time in Patent Office: Days
• US Class Current: 382/133
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G06T 2207/30024 Cell structures in vitro; Tissue sections in vitro
• CPC Class Codes: G06T 7/0012 Biomedical image inspection
• CPC Class Codes: G06T 7/73 using feature-based methods

Abstract

Scanning and analysis of cytology and histology samples uses a flatbed scanner to capture images of the structures of interest such as tumor cells in a manner that results in sufficient image resolution to allow for the analysis of such common pathology staining techniques as ICC (immunocytochemistry), IHC (immunohistochemistry) or in situ hybridization. Very large volumes of such material are scanned in order to identify cells or clusters of cells which are positive or warrant more detailed examination, and if analysis at higher resolution is necessary, information regarding these positive events is transferred to a secondary microscope, such as a conventional scanning microscope, to allow further analysis and review of the selected regions of the slide containing the sample.

Claims

1. A method of analyzing histology or cytology samples positioned on slides, the method comprising:

scanning a plurality of slides with a flatbed scanner using a first set of scanner parameters to capture first image data;

analyzing the first image data to determine the locations on the slides that potentially contain the samples;

scanning at least those portions of the slides that potentially contain the samples with the flatbed scanner using a second set of scanner parameters to capture second image data that contains additional information regarding the samples;

analyzing the second image data to produce information including coordinate information about candidate structures of interest in the sample, the information being referred to as candidate information; and

storing the candidate information for later presentation.

2. The method of claim 1 wherein:

the first set of scanner parameters allows rapid determination of the location of the samples; and

the second set of scanner parameters allows the determination of the candidate information.

3. The method of claim 1 wherein:

the first set of scanner parameters is characterized by a first resolution; and

the second set of scanner parameters is characterized by a second resolution that is higher than the first resolution.

4. The method of claim 1, and further comprising:

for each of at least some candidate structures of interest, storing at least a portion of the second image data that includes that candidate structure of interest; and

displaying at least one stored portion of the second image data that contains a candidate structure of interest.

5. The method of claim 1, and further comprising:

positioning one of the slides that has been determined to contain a candidate structure of interest on a stage; and

using the coordinate information for that candidate structure of interest to position the slide so that the portion of the slide that corresponds to the portion of the second image data containing the given candidate structure of interest is aligned with a field of view of a microscope.

6. The method of claim 5 wherein the coordinate information is electronically transferred to a computer that controls the stage.

7. The method of claim 5 wherein the coordinate information is used in conjunction with a reference/finder grid.

8. The method of claim 1, and further comprising:

retrieving the candidate information generated by analyzing the second image data; and

transferring the coordinate information for candidate structures of interest to a secondary higher magnification system for further analysis of slides containing the candidate structures of interest.

9. The method of claim 1 wherein the samples are one of the group consisting of tissue sections, tissue microarrays, cells containing metaphase chromosomes or metaphase (chromosome) spreads, and prokaryotic cells.

10. The method of claim 1 wherein the structures of interest in the samples are cancer cells.

11. The method of claim 1 wherein the samples are not of human origin but are animal or plant cells or tissues.

13. The method of claim 12, and further comprising:

retrieving the candidate information generated by analyzing the second image data; and

transferring the coordinate information for candidate structures of interest to a secondary higher magnification system for further analysis of slides containing the candidate structures of interest.

14. The method of claim 13 wherein:

the secondary system includes a computer-controlled microscope; and

the coordinate information is used by a computer in the secondary system to control a stage for positioning the slides containing the candidate structures of interest.

15. The method of claim 13 wherein:

the secondary system includes a non-scanning microscope; and

the coordinate information is transferred for manual relocation using a reference/finder grid.

16. The method of claim 12 wherein the samples are one of the group consisting of tissue sections, tissue microarrays, cells containing metaphase chromosomes or metaphase (chromosome) spreads, and prokaryotic cells.

17. The method of claim 12 wherein the structures of interest in the sample are cancer cells.

18. The method of claim 12 wherein the samples are not of human origin but are animal or plant cells or tissues.

20. The method of claim 19 wherein:

the secondary system includes a computer-controlled microscope; and

the coordinate information is used by a computer in the secondary system to control a stage for positioning the slides containing the candidate structures of interest.

21. The method of claim 19 wherein:

the secondary system includes a non-scanning microscope; and

the coordinate information is transferred for manual relocation using a reference/finder grid.

22. The method of claim 19 wherein the samples are one of the group consisting of tissue sections, tissue microarrays, cells containing metaphase chromosomes or metaphase (chromosome) spreads, and prokaryotic cells.

23. The method of claim 19 wherein the structures of interest in the sample are cancer cells.

24. The method of claim 19 wherein the samples are not of human origin but are animal or plant cells or tissues.

29. The method of claim 28, and further presenting this information to the operator.

12. A method of analyzing histology or cytology samples positioned on slides, the method comprising:

scanning a plurality of slides at a first resolution with a flatbed scanner to capture first image data;

analyzing the first image data to determine the locations on the slides that potentially contain the samples;

scanning at least those portions of the slides that potentially contain the samples at a second resolution that is higher than the first resolution on the flatbed scanner to capture second image data;

analyzing the second image data to produce information, referred to as candidate information, that includes, for each candidate structure of interest, coordinate information for that candidate structure of interest and additional attribute information for that candidate structure of interest; and

storing the candidate information for later presentation.

19. A method of analyzing histology or cytology samples positioned on slides to determine candidate structures of interest, the method comprising:

imparting optical properties to objects in the samples so that structures of interest can be recognized by a unique combination of features under specific illumination;

scanning a plurality of slides at a first resolution with a flatbed scanner that provides the specific illumination to capture first image data;

analyzing the first image data to determine the locations on the slides that potentially contain the samples;

scanning at least those portions of the slides that potentially contain the samples at a second resolution that is higher than the first resolution on the flatbed scanner to capture second image data;

analyzing the second image data to find instances of the unique combination of features satisfying a proximity constraint, such instances being designated candidate structures of interest;

for each of at least some candidate structures of interest,

further analyzing the candidate structure of interest to determine at least one characteristic thereof, and

storing candidate information that includes (a) coordinate information of the candidate structure of interest, (b) the at least one characteristic of the candidate structure of interest, and (c) a portion of the second image data containing the candidate structure of interest; and

for each of at least some slides,

retrieving candidate information for a candidate structure of interest on the slide, and

using the coordinate information of the candidate structure of interest to position the slide relative to a secondary system for further analysis.

25. A method of analyzing histology or cytology samples positioned on slides stained to produce enough brightfield contrast to allow recognition of one or more structures of interest in the samples, the method comprising:

scanning the slides with a flatbed scanner to capture digital image data;

storing the position coordinates and images of the cells of interest for further review;

finding the cells of interest by coordinates and further analyzing the cells and capturing additional images at the same or higher magnification or resolution;

analyzing the captured images to produce relevant information on the morphology and reactivity of the analyzed markers on the sample; and

transferring coordinates of areas of interest, derived from analyzing captured images, to a secondary higher magnification system for further analysis and operator review; and

presenting this information to the operator.

26. A method of analyzing histology or cytology samples positioned on one or more slides, the method comprising:

staining the slide with one or more relevant markers to produce enough brightfield contrast to allow recognition of one or more structures of interest in the one or more samples;

scanning the one or more slides and capturing images with a flatbed scanner;

storing the captured images for each of the slides;

analyzing the captured images to produce relevant information on the morphology and/or color of the structures of interest on the sample; and

presenting this information to the operator.

27. A method of analyzing histology and cytology samples positioned on one or more slides, the method comprising:

staining the one or more slides with one or more relevant markers to produce a enough brightfield contrast to recognize one or more structures of interest in the one or more samples;

scanning the one or more slides and capturing images with a flatbed scanner;

storing the position coordinates and images of the cells of interest for further review;

finding the cells of interest by coordinates and further analyzing the cells and capturing additional images at the same or higher magnification or resolution;

analyzing the captured images to produce relevant information on the morphology and reactivity of the analyzed markers on the sample; and

transferring coordinates of areas of interest, derived from analyzing captured images, to a secondary higher magnification system for further analysis and operator review; and

presenting this information to the operator.

28. A method of analyzing histology or cytology samples positioned on one or more slides, the samples having been stained with one or more relevant markers to produce enough brightfield contrast to recognize one or more structures of interest in the one or more samples, the method comprising:

using a flatbed scanner to generate one or more images of at least portions of the one or more slides;

storing the images;

analyzing the images to identify sufficiently large connected components (regions of connected pixels above a threshold) as possible structures of interest;

analyzing connected components so identified using at least one of morphology and color of such connected components to identify possible structures of interest; and

storing information on the location and the morphology and/or color of the possible structures of interest on the sample.

30. A method of analyzing a histology or cytology sample positioned on a slide, the sample having been stained with one or more relevant markers to produce enough brightfield contrast to recognize one or more structures of interest in the one or more samples, the method comprising:

using a flatbed scanner to acquire a first image of the slide at a first resolution;

using a computer to analyze the first image to determine a region of interest of the slide;

using the scanner to acquire a second image of the region of interest at a second resolution that is higher than the first resolution;

using the computer to analyze the second image to determine one or more features in the second image that are candidates for being structures of interest;

using the computer to generate position information for each feature;

using the computer to generate additional information that characterizes an attribute of each feature; and

storing the position information and attribute information for each feature.