Systems and methods for calibrating, configuring and validating an imaging device or system for multiplex tissue assays

Patent metadata

Field	Value
Publication number	US-11566941-B2
Application number	US-202016799608-A
Country	US
Kind code	B2
Filing date	Feb 24, 2020
Priority date	Jan 31, 2013
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

Abstract

A system and method for characterization and/or calibration of performance of a multispectral imaging (MSI) system equipping the MSI system for use with a multitude of different fluorescent specimens while being independent on optical characteristics of a specified specimen and providing an integrated system level test for the MSI system. A system and method are adapted to additionally evaluate and express operational parameters performance of the MSI system in terms of standardized units and/or to determine the acceptable detection range of the MSI system.

First claim

What is claimed:

1. A method comprising:
generating, using an imaging system, a first set of image data corresponding to a tissue sample, wherein the first set of image data is generated based on one or more images captured by the imaging system at a maximum light level of a dynamic range indicated by a sensor of the imaging system at a predetermined exposure time;
generating, using the imaging system, a second set of image data corresponding to the tissue sample, wherein the second set of image data is generated based on one or more images captured by the imaging system at a minimum light level of the dynamic range indicated by the sensor of the imaging system at the predetermined exposure time;
generating, using the imaging system, a third set of image data corresponding to the tissue sample, wherein the third set of image data is generated based on one or more images captured by the imaging system at a medium light level within the dynamic range indicated by the sensor at the predetermined exposure time, and wherein the medium light level is between the maximum light level and the minimum light level;
determining a linear regression value for each of the first, second, and third sets of image data;
identifying, based on the determined linear regression values, an estimated degree of linearity corresponding to the imaging system, wherein the estimated degree of linearity indicates a ratio between signal output of the imaging system and an amount of light received by the imaging system; and
calibrating one or more components of the imaging system based at least in part on the estimated degree of linearity.

2. The method of claim 1 , wherein:
a first image of the one or more images captured by the imaging system at the maximum light level is captured at a first predetermined wavelength; and
a second image of the one or more images captured by the imaging system at the maximum light level is captured at a second predetermined wavelength, wherein the first predetermined wavelength is different from the second predetermined wavelength.

3. The method of claim 1 , further comprising:
identifying a first set of pixel intensity values from the first set of image data;
determining a first set of statistical data of the first set of pixel intensity values; and
determining, based on the first set of statistical data, the linear regression value for the first set of image data.

4. The method of claim 3 , wherein determining the linear regression value for the first set of image data further comprises:
generating a graph corresponding to the first set of image data, wherein:
a first axis of the graph indicates a variance value of the first set of statistical data; and
a second axis of the graph indicates a mode value of the first set of statistical data.

5. The method of claim 1 , wherein determining the linear regression value for each of the first, second, and third sets of image data further comprises generating a conversion value for each of the first, second, and third sets of image data, wherein the conversion value indicates an estimated number of electrons recorded by the sensor of the imaging system at each pixel of a respective image.

6. The method of claim 1 , wherein the sensor is a charge-coupled device sensor that converts photons characterized as an analog signal to an digital signal.

7. The method of claim 1 , wherein the dynamic range indicates a ratio of maximum and minimum light intensity values that the imaging system is capable of converting from an analog signal to a digital signal.

8. A system comprising:
a processing unit comprising one or more processors; and
memory coupled with and readable by the processing unit and storing therein a set of instructions which, when executed by the processing unit, causes the one or more processors to perform operations comprising:
generating, using an imaging system, a first set of image data corresponding to a tissue sample, wherein the first set of image data is generated based on one or more images captured by the imaging system at a maximum light level of a dynamic range indicated by a sensor of the imaging system at a predetermined exposure time;
generating, using the imaging system, a second set of image data corresponding to the tissue sample, wherein the second set of image data is generated based on one or more images captured by the imaging system at a minimum light level of the dynamic range indicated by the sensor of the imaging system at the predetermined exposure time;
generating, using the imaging system, a third set of image data corresponding to the tissue sample, wherein the third set of image data is generated based on one or more images captured by the imaging system at a medium light level within the dynamic range indicated by the sensor at the predetermined exposure time, and wherein the medium light level is between the maximum light level and the minimum light level;
determining a linear regression value for each of the first, second, and third sets of image data;
identifying, based on the determined linear regression values, an estimated degree of linearity corresponding to the imaging system, wherein the estimated degree of linearity indicates a ratio between signal output of the imaging system and an amount of light received by the imaging system; and
calibrating one or more components of the imaging system based at least in part on the estimated degree of linearity.

9. The system of claim 8 , wherein:
a first image of the one or more images captured by the imaging system at the maximum light level is captured at a first predetermined wavelength; and
a second image of the one or more images captured by the imaging system at the maximum light level is captured at a second predetermined wavelength, wherein the first predetermined wavelength is different from the second predetermined wavelength.

10. The system of claim 8 , wherein the memory stores additional instructions which, when executed by the processing unit, causes the one or more processors to perform operations comprising:
identifying a first set of pixel intensity values from the first set of image data;
determining a first set of statistical data of the first set of pixel intensity values; and
determining, based on the first set of statistical data, the linear regression value for the first set of image data.

11. The system of claim 10 , wherein determining the linear regression value for the first set of image data further comprises:
generating a graph corresponding to the first set of image data, wherein:
a first axis of the graph indicates a variance value of the first set of statistical data; and
a second axis of the graph indicates a mode value of the first set of statistical data.

12. The system of claim 8 , wherein determining the linear regression value for each of the first, second, and third sets of image data further comprises generating a conversion value for each of the first, second, and third sets of image data, wherein the conversion value indicates an estimated number of electrons recorded by the sensor of the imaging system at each pixel of a respective image.

13. The system of claim 8 , wherein the sensor is a charge-coupled device sensor that converts photons characterized as an analog signal to an digital signal.

14. The system of claim 8 , wherein the dynamic range indicates a ratio of maximum and minimum light intensity values that the imaging system is capable of converting from an analog signal to a digital signal.

15. A computer-program product tangibly embodied in a non-transitory machine-readable storage medium, inclu

Assignees

• Ventana Med Syst Inc

Inventors

• Garsha Karl
• Otter Michael

Classifications

• G01N21/274

  Calibration, base line adjustment, drift correction · CPC title

• G01J3/2823

  Imaging spectrometer · CPC title

• G01J3/0297 Primary

  Constructional arrangements for removing other types of optical noise or for performing calibration · CPC title

• G01J2003/2826

  Multispectral imaging, e.g. filter imaging · CPC title

• G01J3/44

  Raman spectrometry; Scattering spectrometry {; Fluorescence spectrometry} · CPC title