Methods for feature analysis on consecutive tissue sections

• US 8,787,651 B2
• Filed: 09/28/2011
• Issued: 07/22/2014
• Est. Priority Date: 09/28/2010
• Status: Active Grant

• Current Assignee: Flagship Biosciences, Inc.
• Original Assignee: Flagship Biosciences, LLC
• Inventors: Potts, Steven, Johnson, Trevor, Voelker, Frank, Young, George David
• Primary Examiner(s): Bella, Matthew
• Assistant Examiner(s): HEIDEMANN, JASON E
• Application Number:
  US13/247,991
• Publication Number:
  US 20120076390A1
• Time in Patent Office: 1,028 Days
• Field of Search: None
• US Class Current: 382/133
• CPC Class Codes: G06T 2207/10056 Microscopic image
• CPC Class Codes: G06T 2207/20104 Interactive definition of region of interest [ROI]
• CPC Class Codes: G06T 2207/30096 Tumor; Lesion
• CPC Class Codes: G06T 7/0014 using an image reference approach
• CPC Class Codes: G06T 7/38 Registration of image sequences

Abstract

Feature analysis on consecutive tissue sections (FACTS) includes obtaining a plurality of consecutive tissue sections from a tissue sample, staining the sections with at least one biomarker, obtaining a digital image thereof, and identifying one or more regions of interest within a middle of the consecutive tissue sections. The digital images of the consecutive tissue sections are registered for alignment and the one or more regions of interest are transferred from the image of the middle section to the images of the adjacent sections. Each image of the consecutive tissue sections is then analyzed and scored as appropriate. Using FACTS methods, pathologist time for annotation is reduced to a single slide. Optionally, multiple middle sections may be annotated for regions of interest and transferred accordingly.

Claims

1. A method for feature analysis on consecutive tissue sections, comprising:

obtaining a tissue specimen for analysis;

sectioning said tissue specimen into at least three consecutive tissue sections comprising a first tissue section, a second tissue section, and a third tissue section, said second tissue section originating from a volume of said tissue specimen between said first and third tissue sections;

applying at least a first biomarker to the first tissue section of said consecutive tissue sections, applying at least a second biomarker to the second tissue section, and applying at least a third biomarker to the third tissue section;

using a digital image analysis system comprising a camera and a display screen to capture at least a first digital image of the first tissue section, a second digital image of the second tissue section and a third digital image of the third tissue section; and

registering the digital images of the first and third tissue sections with the digital image of said second tissue section to digitally align each of the images;

characterized in that the method further comprises;

annotating one or more regions of interest within the second digital image of the second tissue section;

transferring said one or more annotated regions of interest from the second digital image to at least one of the first and third digital images that are digitally aligned therewith; and

deriving a tissue analysis score for each of said consecutive tissue sections.

2. The method of claim 1, wherein said obtaining a tissue specimen comprises preparing a tissue sample in a paraffin block and thinly slicing each of said consecutive tissue sections therefrom.

3. The method of claim 1, wherein said at least three consecutive tissue sections comprises five consecutive tissue sections.

4. The method of claim 1, wherein said first through third biomarkers are each distinct from one another.

5. The method of claim 1, wherein said deriving a tissue analysis score comprises executing an algorithm programmed within said digital analysis system to quantify one or more pixilated areas within the annotated region of interest from at least one of said digital images.

6. The method of claim 1, wherein said annotating one or more regions of interest comprises at least one of:

selecting one or more cells or groups of cells having a specific cell type.

7. The method of claim 1, wherein said annotating one or more regions of interest comprises at least one of:

selecting one or more cells or groups of cells having a specific antibody marker or stain.

8. The method of claim 1, wherein said deriving a tissue analysis score comprises:

with the regions of interest being transferred from the second digital image to each of the first and third digital images,

scoring said first digital image at said regions of interest to determine a first score associated with a first protein; and

scoring said third digital image at said regions of interest to determine a second score associated with a second protein;

said first and second proteins being distinct from one another.

9. The method of claim 8, wherein each of said first and second scores comprise an immunohistochemistry (IHC) score.

10. The method of claim 8, further comprising combining at least said first score and said second score to report a combined score.

11. The method of claim 1, wherein said second tissue section is stained with an antibody for endothelial tissue such that said regions of interest of the second digital image correspond to vascularity of the second tissue section;

wherein said regions of interest of the second digital image are transferred to said first and third aligned digital images, respectively;

said first tissue section being stained to identify one or more first cells, and said third tissue section being stained to identify one or more second cells, said first and second cells being distinct from one another, and deriving a score representative of the percentage of first and second cells that are within a given range of the vasculature.

12. The method of claim 1, wherein the second tissue section comprises a section of tissue about an implanted medical device;

the second tissue section is stained with hematoxylin and eosin;

at least one of the first and second tissue sections is stained with an antibody or marker associated with one of;

inflammation, plasma cells, macrophages, necrosis, or fibrosis;

the second digital image corresponding to the second tissue section is annotated to identify the regions of interest about portions of the implanted medical device within the second tissue section;

said regions of interest are transferred to the first and third digital images corresponding to the first and third tissue sections;

wherein said deriving a tissue analysis score for each of said consecutive tissue sections comprises quantifying inflammation within the regions of interest of the first and third digital images.

13. The method of claim 1, wherein said regions of interest of the second digital image are transferred to said first and third aligned digital images, respectively;

said first tissue section being stained to identify one or more first cells, and said third tissue section being stained to identify one or more second cells, said first and second cells being distinct from one another, and deriving a score representative of the percentage of first and second cells.