Data management in a linear-array-based microscope slide scanner

• US 8,094,902 B2
• Filed: 05/24/2011
• Issued: 01/10/2012
• Est. Priority Date: 05/03/2000
• Status: Expired due to Term

• Current Assignee: Leica Biosystems Imaging Inc. (Danaher Corporation)
• Original Assignee: Aperio Technologies Incorporated (Danaher Corporation)
• Inventors: Crandall, Greg J., Eichhorn, Ole, Olson, Allen H., Soenksen, Dirk G.
• Primary Examiner(s): Lu, Tom Y
• Application Number:
  US13/114,998
• Publication Number:
  US 20110221882A1
• Time in Patent Office: 231 Days
• Field of Search: 382/128
• US Class Current: 382/128
• CPC Class Codes: G02B 21/002 Scanning microscopes scanning near field optical microscopes G01Q60/18
• CPC Class Codes: G02B 21/0036 Scanning details, e.g. scanning stages
• CPC Class Codes: G02B 21/008 Details of detection or image processing, including general computer control
• CPC Class Codes: G02B 21/14 affording illumination for phase-contrast observation
• CPC Class Codes: G02B 21/245 using auxiliary sources, detectors
• CPC Class Codes: G02B 21/26 Stages; Adjusting means therefor
• CPC Class Codes: G02B 21/32 Micromanipulators structurally combined with microscopes
• CPC Class Codes: G02B 21/34 Microscope slides, e.g. mounting specimens on microscope slides
• CPC Class Codes: G02B 21/365 Control or image processing arrangements for digital or video microscopes G02B21/361, G02B21/362 take precedence
• CPC Class Codes: G02B 21/367 providing an output produced by processing a plurality of individual source images, e.g. image tiling, montage, composite images, depth sectioning, image comparison
• CPC Class Codes: H04N 1/053 in main scanning direction, e.g. synchronisation of line start or picture elements in a line
• CPC Class Codes: H04N 1/1903 Arrangements for enabling electronic abutment of lines or areas independently scanned by different elements of an array or by different arrays
• CPC Class Codes: H04N 1/193 using electrically scanned linear arrays , e.g. linear CCD arrays
• CPC Class Codes: H04N 1/19573 Displacing the scanned image
• CPC Class Codes: H04N 2201/04727 on a linear encoder
• CPC Class Codes: H04N 2201/04755 by controlling the position or movement of a scanning element or carriage, e.g. of a polygonal mirror, of a drive motor
• CPC Class Codes: H04N 23/56 provided with illuminating means
• CPC Class Codes: H04N 23/631 Graphical user interfaces [GUI] specially adapted for controlling image capture or setting capture parameters
• CPC Class Codes: H04N 23/635 Region indicators; Field of view indicators
• CPC Class Codes: H04N 23/661 Transmitting camera control signals through networks, e.g. control via the Internet
• CPC Class Codes: H04N 7/18 : Closed-circuit television [CCTV] systems, i.e. systems in which the video signal is not broadcast
• CPC Class Codes: H04N 7/183 : for receiving images from a single remote source

Abstract

Systems and methods for processing, storing, and viewing extremely large imagery data rapidly produced by a linear-array-based microscope slide scanner are provided. The system receives, processes, and stores imagery data produced by the linear scanner as a series of overlapping image stripes and combines the data into a seamless and contiguous baseline image. The baseline image is logically mapped into a plurality of regions that are individually addressed to facilitate viewing and manipulation of the baseline image. The system enables dynamic imagery data compression while scanning and capturing new image stripes that eliminates the overhead associated with storing uncompressed image stripes. The system also creates intermediate level images, thereby organizing the baseline image into a variable level pyramid structure referred to as a virtual slide. The system facilitates the use of virtual slides in applications such as telemedicine, telepathology, microscopy education, and analysis of high value specimens like tissue arrays.

Claims

1. A system for capturing imagery data using a line scan camera, comprising:

at least one memory for imagery data;

a motorized stage configured to support a microscope sample and move the microscope sample in an X axis direction and a Y axis direction;

an objective lens positioned for viewing a portion of the microscope sample;

a line scan camera optically coupled to the objective lens and configured to capture imagery data of the microscope sample as a plurality of image stripes where each image stripe comprises a plurality of scan lines;

a positioning element configured to adjust a position of the objective lens in a Z axis direction; and

a processor configured to instruct the positioning element to adjust the position of the objective lens in the Z axis during capture of a first stripe of imagery data and a second stripe of imagery data, the processor further configured to store a first plurality of image portions from the first stripe and a second plurality of image portions from the second stripe as a contiguous digital image in said at least one memory.

2. The system of claim 1, wherein the processor is configured to instruct the positioning element to adjust the position of the objective lens between adjacent scan lines in an image stripe.

3. The system of claim 1, wherein the positioning element is a piezo positioner.

4. The system of claim 1 wherein the processor is further configured to:

acquire the plurality of image stripes from the line scan camera, wherein adjacent stripes overlap defining corresponding overlap areas;

combine the plurality of stripes into a contiguous image, wherein combining comprises for each adjacent pair of stripes;

identify a first subset of pixels in a first stripe in an overlap area,

identify a second subset set of in a second stripe in the overlap area,

determine an offset between the first and second stripes based on one or more comparisons of the first and second subsets of pixels,

align the first and second stripes based on the offset, and

store the contiguous image in the at least one memory.

5. The system of claim 4, wherein the processor is further configured to combine the plurality of stripes while acquiring the plurality of stripes from the line scan camera.

6. The system of claim 4, wherein the processor is further configured to compress one or more of the plurality of stripes while acquiring the plurality of stripes.

7. The system of claim 4, wherein each stripe comprises a height and a width, and wherein the height of the first stripe is not equal to the height of the second stripe.

8. The system of claim 4, wherein the processor is configured to identify the first subset of pixels by identifying pixels in the first stripe in the overlap area having a high local intensity gradient value.

9. The system of claim 4, wherein the processor is configured to determine the offset by:

computing an error sum between the first and second set of pixels using a plurality of potential offsets; and

selecting the offset corresponding to the lowest computed error sum.

10. A non-transitory computer readable medium having stored thereon one or more sequences of instructions for causing one or more processors to perform the steps for capturing imagery data using a line scan camera, the steps comprising:

determining a ramp-up period required to accelerate a microscope stage to a substantially constant velocity;

accelerating the microscope stage through the ramp-up period, wherein said ramp-up period is less than 1 mm of travel;

capturing imagery data using a line scan camera and an objective lens while the stage is traveling at substantially constant velocity; and

adjusting the objective lens in a Z axis direction during the capture of the imagery data.

11. The medium of claim 10, further comprising adjusting the position of the objective lens between adjacent scan lines in an image stripe.

12. The medium of claim 10, further comprising acquiring the plurality of image stripes from the line scan camera, wherein adjacent stripes overlap to define corresponding overlap areas;

and combining the plurality of stripes into a contiguous image.

13. The medium of claim 12, wherein combining the plurality of stripes into a contiguous image further comprises:

identifying a first subset of pixels in a first stripe in an overlap area;

identifying a second subset set of in a second stripe in the overlap area;

determining an offset between the first and second stripes based on one or more comparisons of the first and second subsets of pixels; and

aligning the first and second stripes based on the offset.

14. The medium of claim 13, further comprising combining the plurality of stripes while acquiring the plurality of stripes from the line scan camera.

15. The medium of claim 13, further comprising compressing at least a portion of the aligned stripes and storing the aligned stripes as a contiguous digital image.

16. The medium of claim 13, wherein each stripe comprises a height and a width, and wherein the height of the first stripe is not equal to the height of the second stripe.

17. The medium of claim 13, wherein identifying the first subset of pixels comprises identifying pixels in the first stripe in the overlap area having a high local intensity gradient value.

18. The medium of claim 13, wherein determining the offset comprises:

computing an error sum between the first and second set of pixels using a plurality of potential offsets; and

selecting the offset corresponding to the lowest computed error sum.

19. A system for capturing imagery data, comprising:

means for storing imagery data;

means for moving a microscope sample in an X axis direction and a Y axis direction;

objective lens means for viewing a portion of the microscope sample;

line scan camera means optically coupled to the objective lens means for capturing imagery data of the microscope sample as a plurality of image stripes where each image stripe comprises a plurality of scan lines;

means for adjusting a position of the objective lens in a Z axis direction; and

means for instructing the positioning element to adjust the position of the objective lens in the Z axis during capture of a first stripe of imagery data and a second stripe of imagery data; and

means for storing a first plurality of image portions from the first stripe and a second plurality of image portions from the second stripe as a contiguous digital image in said means for storing imagery data.

20. The system of claim 19, wherein the means for instructing the positioning element is configured to instruct the positioning element to adjust the position of the objective lens between adjacent scan lines in an image stripe.

21. The system of claim 19, wherein the means for adjusting a position of the objective lens is a piezo positioner.

22. The system of claim 19, wherein the means for storing a first plurality of image portions is further configured to:

acquire the plurality of image stripes from the line scan camera, wherein adjacent stripes overlap defining corresponding overlap areas;

combine the plurality of stripes into a contiguous image, wherein combining comprises for each adjacent pair of stripes;

identify a first subset of pixels in a first stripe in an overlap area,

identify a second subset set of in a second stripe in the overlap area,

determine an offset between the first and second stripes based on one or more comparisons of the first and second subsets of pixels,

align the first and second stripes based on the offset, and

store the contiguous image in the means for storing.

23. The system of claim 22, wherein the means for storing a first plurality of image portions is further configured to combine the plurality of stripes while acquiring the plurality of stripes from the line scan camera means.

24. The system of claim 22, wherein the means for storing a first plurality of image portions is further configured to compress one or more of the plurality of stripes while acquiring the plurality of stripes.

25. The system of claim 22, wherein each stripe comprises a height and a width, and wherein the height of the first stripe is not equal to the height of the second stripe.

26. The system of claim 22, wherein the means for storing a first plurality of image portions is further configured to identify the first subset of pixels by identifying pixels in the first stripe in the overlap area having a high local intensity gradient value.

27. The system of claim 22, wherein the wherein the means for storing a first plurality of image portions is further configured to determine the offset by:

computing an error sum between the first and second set of pixels using a plurality of potential offsets; and

selecting the offset corresponding to the lowest computed error sum.