Systems for analyzing microtissue arrays

• US 7,171,030 B2
• Filed: 02/05/2003
• Issued: 01/30/2007
• Est. Priority Date: 11/30/2000
• Status: Expired due to Fees

• Current Assignee: Rutgers University
• Original Assignee: University of Medicine and Dentistry of New Jersey (State of New Jersey)
• Inventors: Foran, David J., Chen, Wenjin
• Primary Examiner(s): Wu; Jingge
• Assistant Examiner(s): Tabatabai; Abolfazl
• Application Number:
  US10/358,935
• Publication Number:
  US 20030118222A1
• Time in Patent Office: 1,455 Days
• Field of Search: 382128-134, 382/151, 382/172, 382/284, 382/294, 435/6, 435/13, 435/64, 435/91.1, 345/169, 345/172, 235/476, 235/470, 702/19, 702/20, 702/21, 702/27, 709/213, 128/920
• US Class Current: 382/128
• CPC Class Codes: G06F 18/00 Pattern recognition
• CPC Class Codes: G06T 2207/30072 Microarray; Biochip, DNA array; Well plate
• CPC Class Codes: G06T 7/00 Image analysis
• CPC Class Codes: G16H 10/40 for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: G16H 30/20 for handling medical images, e.g. DICOM, HL7 or PACS
• CPC Class Codes: G16H 30/40 for processing medical images, e.g. editing

Abstract

A tissue microarray imaging system autonomously images, analyzes, and stores data for samples in a tissue microarray. The system may include a tissue microarray, a robotic microscope, and an imaging workstation that executes software to automatically control operation of the microscope to capture images from the microarray and analyze image results. A low magnification may be used to register samples within the microarray and obtain coordinates for each tissue specimen. Progressively higher magnifications may be used to analyze images of each registered specimen. Where multiple dyes are used to stain specimens, color separation techniques may be applied to independently measure and analyze each staining intensity. Images and quantitative data from the images may then be stored in a relational database for subsequent review. The system may be local, or may be Web-based for distributed control and sharing of results.

Claims

1. A method comprising:

staining a tissue microarray with a first stain and a second stain to obtain a stained tissue microarray, each of the first stain and the second stain selectively staining portions of the tissue microarray;

capturing an image of the stained tissue microarray, the image including a plurality of specimen images;

analyzing the image to identify a first color vector corresponding to the first stain and a second color vector corresponding to the second stain; and

measuring a presence of each one of the first color vector and the second color vector in one or more of the plurality of specimen images.

2. The method of claim 1 wherein the image comprises a plurality of digital images captured by an imaging device and combined into a composite image of the stained tissue microarray.

3. The method of claim 1 wherein capturing an image further comprises capturing an image with a robotic microscope.

4. The method of claim 1 wherein one of the first stain or the second stain is a histochemical stain.

5. The method of claim 1 wherein one of the first stain or the second stain is an immunologic stain.

6. The method of claim 1 wherein one of the first stain or the second stain selectively stains one or more features of diagnostic interest.

7. The method of claim 1 wherein analyzing the digital image further comprises transforming image data into a polar coordinate space and identifying peak color vectors within the polar coordinate space.

8. The method of claim 1 further comprising displaying one of the plurality of specimen images and a selected one of the first stain or the second stain.

9. The method of claim 1 wherein measuring a presence of each one of the first color vector and the second color vector in one of the plurality of specimen images comprises comparing the first color vector and the second color vector to the one of the plurality of specimen images on a pixel-by-pixel basis, thereby providing a staining vector for each pixel of the specimen image.

10. A computer program embodied in a computer readable medium comprising:

computer executable code for capturing an image of a stained tissue microarray stained with a first stain and a second stain, the image including a plurality of specimen images;

computer executable code for analyzing the image to identify a first color vector corresponding to the first stain and a second color vector corresponding to the second stain; and

computer executable code for measuring a presence of each one of the first color vector and the second color vector in one or more of the plurality of specimen images.

11. A system comprising:

staining means for staining a tissue microarray with a first stain and a second stain to obtain a stained tissue microarray, each of the first stain and the second stain selectively staining portions of the tissue microarray;

imaging means for capturing an image of the stained tissue microarray, the image including a plurality of specimen images;

first computing means for analyzing the image to identify a first color vector corresponding to the first stain and a second color vector corresponding to the second stain; and

second computing means for measuring a presence of each one of the first color vector and the second color vector in one or more of the plurality of specimen images.

12. A system comprising an imaging device and a computer, the imaging device responsive to a control signal to provide images at a specified magnification and a specified location within a tissue microarray, and the computer providing the control signal to the imaging device and receiving the images provided by the imaging device, the computer configured to analyze images of the tissue microarray to identify one or more color vectors associated with one or more dyes used to stain the tissue microarray, the computer further configured to capture a specimen image of each one of one or more specimens within the tissue microarray and to measure a presence of each one of the one or more color vectors within each specimen image.

13. The system of claim 12 wherein the imaging device includes a robotic microscope.

14. The system of claim 12 wherein the imaging device includes a virtual microscope.

15. The system of claim 12 wherein the imaging device is further responsive to a control signal received through a connection to a network, the imaging device being controlled from a remote location through a web-based interface.

16. The system of claim 12 wherein the system identifies the color vector associated with each of the one or more dyes by transforming digital image data from the images of the tissue microarray into a polar coordinate space and analyzing the transformed digital image data to identify a peak.

17. The system of claim 12 further comprising a database for storing in a structured form digital image data from the tissue microarray, data concerning physical properties and preparation of the tissue microarray, and data derived from the digital image data.

18. The system of claim 12 wherein the computer is further configured to generate a processed image that includes on of the specimen images and, superimposed on the specimen image, a selected one of the dyes used to stain the tissue microarray.

19. The system of claim 18 further comprising a display connected to the computer and displaying the processed image.

20. The system of claim 12 wherein the one or more dyes used to stain the tissue microarray selectively stain one or more features of diagnostic interest.

21. A method comprising:

staining a tissue microarray with a first stain and a second stain to obtain a stained tissue microarray, each of the first stain and the second stain selectively staining portions of the tissue microarray;

capturing an image of the stained tissue microarray, the stained tissue microarray including a plurality of discs, each disc including a sample of a biological specimen;

locating a first group of discs from the plurality of discs using one or more visual features of the first group of discs;

identifying a grid defined by the first group of discs;

locating a second group of discs from the plurality of discs using the grid to locate discs which do not include the one or more visual features of the first group of discs;

capturing a specimen image of each one of the first group of discs and the second group of discs to provide a plurality of specimen images;

analyzing the image of the stained tissue microarray to identify a first color vector corresponding to the first stain and a second color vector corresponding to the second stain; and

measuring a presence of each one of the first color vector and the second color vector in one or more of the plurality of specimen images.