System and method for gross anatomic pathology using hyperspectral imaging

• US 9,274,046 B2
• Filed: 12/03/2013
• Issued: 03/01/2016
• Est. Priority Date: 04/30/2010
• Status: Active Grant

• Current Assignee: Chemimage Corporation
• Original Assignee: Chemimage Corporation
• Inventors: Stewart, Shona, Treado, Patrick, Kirschner, Heather, Wilson, Alan, Priore, Ryan, Cohen, Jeffrey, Augustine, Serena
• Primary Examiner(s): Nur, Abdullahi
• Application Number:
  US13/998,776
• Publication Number:
  US 20140093147A1
• Time in Patent Office: 819 Days
• Field of Search: 356300-445, 356 72- 73
• US Class Current: 1/1
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01J 3/0224 using polarising or depolarising elements
• CPC Class Codes: G01J 3/32 Investigating bands of a spectrum in sequence by a single detector
• CPC Class Codes: G01J 3/44 Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
• CPC Class Codes: G01N 21/21 Polarisation-affecting properties G01N21/19 takes precedence
• CPC Class Codes: G01N 21/255 Details, e.g. use of specially adapted sources, lighting or optical systems
• CPC Class Codes: G01N 21/314 with comparison of measurements at specific and non-specific wavelengths dual wavelength spectrometry G01J3/427
• CPC Class Codes: G01N 21/33 using ultraviolet light G01N21/39 takes precedence
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence
• CPC Class Codes: G01N 21/3581 using far infrared light; using Terahertz radiation
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G02B 21/0092 Polarisation microscopes
• CPC Class Codes: G02B 21/16 adapted for ultraviolet illumination ; Fluorescence microscopes G02B21/0076 takes precedence
• CPC Class Codes: G02B 21/361 Optical details, e.g. image relay to the camera or image sensor G02B21/364 takes precedence; illumination details G02B21/06 and subgroups

Abstract

A method for analyzing organ samples using hyperspectral imaging comprising illuminating an organ sample to generate interacted photons, collecting the interacted photons and passing the interacted photons through a tunable filter. The filtered interacted photons are detected to generate a hyperspectral image. A brightfield image is generated and associated with the hyperspectral image. Spectra from locations of interest are extracted and analyzed to assess a characteristic of the organ sample. A system may comprise an illumination source to illuminate an organ sample and generate interacted photons, a collection optics for collecting the interacted photons and a tunable filter to filter the interacted photons. A detector is configured to detect the filtered photons and generate at least one hyperspectral image. The detector may also be configured to generate at least one brightfield image representative of the organ sample.

Claims

1. A method of analyzing a biological organ, the method comprising:

illuminating the biological organ to generate a first plurality of interacted photons;

collecting the first plurality of interacted photons to generate a first optical signal;

separating the first optical signal into a plurality of orthogonally polarized optical components;

filtering the plurality of optical components into a plurality of passband wavelengths to generate a plurality of filtered photons;

detecting the plurality of filtered photons to generate at least one hyperspectral image; and

analyzing the at least one hyperspectral image by extracting a spectrum from a location in the at least one hyperspectral image, wherein the location corresponds to an area of interest of the biological organ, and analyzing the extracted spectrum to identify a characteristic of the biological organ.

2. The method of claim 1, wherein the biological organ comprises one or more of a kidney, a ureter, a prostate, a penis, a testicle, a bladder, a heart, a brain, a liver, a lung, a colon, an intestine, a pancreas, a thyroid, an adrenal gland, a spleen, a stomach, a uterus, and an ovary.

3. The method of claim 1, further comprising generating a bright-field image representative of the biological organ.

4. The method of claim 3, further comprising analyzing the bright-field image to identify one or more of a morphological feature of the biological-organ and an anatomical feature of the biological organ.

5. The method of claim 1, wherein analyzing the extracted spectrum further comprises comparing the extracted spectrum to a reference spectrum associated with a known characteristic.

6. The method of claim 5, wherein the comparing comprises applying an algorithmic technique.

7. The method of claim 6, wherein the algorithmic technique comprises support vector machines.

8. The method of claim 6, wherein the algorithmic technique comprises a chemometric technique.

9. The method of claim 8, wherein the chemometric technique comprises one or more of a multivariate curve resolution analysis, a principle component analysis (PCA), a partial least squares discriminant analysis (PLSDA), a k means clustering analysis, a band t. entropy method analysis, an adaptive subspace detector analysis, a cosine correlation analysis, an Euclidian distance analysis, a partial least squares regression analysis, a spectral mixture resolution analysis, a spectral angle mapper metric analysis, a spectral information divergence metric analysis, a Mahalanobis distance metric analysis, and a spectral unmixing analysis.

10. The method of claim 8, wherein the chemometric technique is applied to spectra corresponding to each pixel of the at least one hyperspectral image to generate at least one score image.

11. The method of claim 10, wherein the score image comprises one or more of a target image and a non-target image.

12. The method of claim 11, further comprising applying a threshold to the target image to generate a class image of the biological organ.

13. The method of claim 11, further comprising generating an RGB image of the biological organ, wherein at least one channel of the RGB image corresponds to the target image.

14. The method of claim 11, further comprising generating an RGB image of the biological organ, wherein at least one channel of the RGB image corresponds to a non-target image.

15. The method of claim 1, wherein at least two hyperspectral images are generated and the analyzing comprises applying at least one ratiometric technique.

16. The method of claim 1, wherein the characteristic comprises an anatomical feature of the biological organ.

17. The method of claim 1, wherein the characteristic comprises one or more of a tumor and a non-tumor.

18. The method of claim 17, wherein the tumor comprises one or more of a cancerous tumor and a non-cancerous tumor.

19. The method of claim 1, wherein the characteristic comprises a tumor margin.

20. The method of claim 1, wherein the hyperspectral image comprises a VIS-NIR hyperspectral image.

21. The method of claim 1, wherein the plurality of orthogonally polarized optical components comprises a first optical component and a second optical component, and the filtering comprises transmitting the first optical component to a first optical filter to generate a first portion of the plurality of filtered photons and transmitting the second optical component to a second optical filter to generate a second portion of the plurality of filtered photons.

22. The method of claim 21, wherein detecting the plurality of filtered photons comprises detecting the first portion of the plurality of filtered photons with a first detector and detecting the second portion of the plurality of filtered photons with a second detector.

23. The method of claim 21, wherein the first portion of the plurality of filtered photons and the second portion of the plurality of filtered photons are detected substantially simultaneously.

24. The method of claim 21, wherein the first portion of the plurality of filtered photons and the second portion of the plurality of filtered photons are detected sequentially.

25. The method of claim 21, wherein the hyperspectral image generated from the first portion of the plurality of filtered photons and the hyperspectral image generated from the second portion of the plurality of filtered photons are overlaid.

26. The method of claim 21, wherein the hyperspectral image generated from the first portion of the plurality of filtered photons and the hyperspectral image generated from the second portion of the plurality of filtered photons are not overlaid.

27. The method of claim 1, wherein filtering comprises passing the plurality of optical components through a tunable filter further comprising one or more of a fixed filter and a tunable filter.

28. A system for analyzing a biological organ, the system comprising:

an illumination source configured to illuminate the biological organ and generate a first plurality of interacted photons;

a collection optic configured to collect the first plurality of interacted photons and generate a first optical signal;

a beam splitter configured to separate the first optical signal into a plurality of optical components;

a plurality of filters, wherein each filter is configured to filter one of the plurality of optical components into a passband wavelength to generate a plurality of filtered components;

one or more detectors configured to detect the plurality of filtered components and generate at least one hyperspectral image; and

a processor configured to analyze the at least one hyperspectral image by extracting a spectrum from a location in the at least one hyperspectral image, wherein the location corresponds to an area of interest of the biological organ, and analyzing the extracted spectrum to identify a characteristic of the biological organ.

29. The system of claim 28, wherein the plurality of optical components comprises a first optical component having a first polarization alignment and a second optical component having a second polarization alignment.

30. The system of claim 29, wherein the plurality of filters comprises a first filter configured to receive the first optical component and transmit at least a portion of the first optical component having a first wavelength and a second filter configured to receive the second optical component and transmit at least a portion of the second optical component having a second wavelength.

31. The system of claim 30, wherein the one or more detectors comprises a detector configured to detect the first optical component and the second optical component.

32. The system of claim 30, wherein the one or more detectors comprises a first detector configured to detect the first optical component and a second detector configured to detect the second optical component.

33. The system of claim 28, wherein the illumination source comprises one or more of a metal halide arc lamp and a quartz tungsten halogen lamp.

34. The system of claim 28, further comprising a tissue bin configured to hold the biological organ.

35. The system of claim 28, wherein the collection optic comprises a zoom lens.

36. The system of claim 28, further comprising a controller configured to tune one or more of the plurality of filters to at least one wavelength band.

37. The system of claim 36, wherein the controller is further configured to tune one or more of the plurality of filters to a wavelength band in the range of about 400 nm to about 1100 nm.

38. The system of claim 28, wherein one or more of the plurality of filters comprises one or more of a fixed filter and a tunable filter.

39. The system of claim 38, wherein the tunable filter further comprises one or more of a Fabry Perot angle tunable filter, an acousto-optic tunable filter, a liquid crystal tunable filter, a Lyot filter, an Evans split element liquid crystal tunable filter, a Solc liquid crystal tunable filter, a fixed wavelength Fabry Perot tunable filter, an air-tuned Fabry Perot tunable filter, a mechanically-tuned Fabry Perot tunable filter, and a liquid crystal Fabry Perot tunable filter.

40. The system of claim 28, wherein the one or more detectors comprise an InGaAs detector, a photodiode array detector, a CMOS detector, an InSb detector, a CCD detector, an ICCD detector, and an MCT detector.

41. The system of claim 28, wherein the processor further comprises at least one reference data set wherein each reference data set is associated with a known characteristic.

42. The system of claim 28, wherein the processor is further configured to compare the extracted spectrum to the at least one reference data set.

43. The system of claim 28, wherein the one or more detectors are further configured to generate a bright field image of the biological organ.

44. A system comprising:

a processor; and

a non-transitory data storage medium containing program code, which, when executed by a processor, causes the processor to;

illuminate a biological organ to generate a plurality of interacted photons;

collect the plurality of interacted photons to generate a first optical signal;

transmit the first optical signal through a beam splitter to separate the first optical signal into a plurality of optical components;

pass the plurality of optical components through a plurality of tunable filters, wherein each filter is configured to filter one of the plurality of optical components into a passband wavelength to generate a plurality of filtered components;

detect the plurality of filtered components with one or more detectors to generate at least one hyperspectral image;

generate a bright field image representative of the biological organ;

align the bright field image with the at least one hyperspectral image;

extract a spectrum from a location of the at least one hyperspectral image, wherein each location corresponds to an area of interest of the biological organ;

analyze the extracted spectrum to identify a characteristic of the biological organ.

45. The system of claim 44, wherein the storage medium further contains one or more programming instructions that, when executed, cause the processor to:

transmit a first optical component of the plurality of optical components to a first tunable filter and a second optical component of the plurality of optical components to a second optical filter.