Method for Raman chemical imaging of endogenous chemicals to reveal tissue lesion boundaries in tissue

• US 20030004419A1
• Filed: 06/28/2002
• Published: 01/02/2003
• Est. Priority Date: 06/28/2001
• Status: Active Grant

• Current Assignee: Chemimage Corporation
• Original Assignee: Chemimage Corporation
• Inventors: Nelson, Matthew P., Treado, Patrick J.
• Granted Patent: US 6,965,793 B2
• Time in Patent Office: Days
• US Class Current: 600/476
• CPC Class Codes: A61B 5/0091 for mammography
• CPC Class Codes: A61B 5/4312 Breast evaluation or disorder diagnosis A61B5/0091 takes precedence
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

Apparatus and methods for spatially resolved Raman detection of molecules indicative of the borders of lesions with normal tissue are disclosed. A region of biological tissue was illuminated with monochromatic light. A Raman shifted light signal is detected from endogenous molecules in the region, the molecules being spatially organized in a localized first area of the region. These molecules are indicative of a border between normal tissue and a lesion. The Raman shifted light signal is then spatially resolved in at least one direction.

Claims

1. A method, comprising:

a) illuminating a region of biological tissue with monochromatic light;

then

b) detecting a Raman shifted light signal from endogenous molecules in the region, the molecules spatially organized in a localized first area of the region, the molecules indicative of a border between normal tissue and a lesion; and

c) spatially resolving the Raman shifted light signal in at least one direction.

2. The method of claim 1, where the region is imaged.

3. The method of claim 2, where the Raman shifted light from the region passes through a FAST fiber array spectral translator.

4. The method of claim 2, where the Raman shifted light from the region passes through a Fabry Perot tunable filter.

5. The method of claim 2, where the Raman shifted light from the region passes through an acousto-optic tunable filter.

6. The method of claim 2, where the Raman shifted light from the region passes through a liquid crystal tunable filter.

7. The method of claim 6, where the Raman shifted light from the region passes through a Lyot filter.

8. The method of claim 7, where the Raman shifted light from the region passes through an Evan'"'"'s split element liquid crystal tunable filter.

9. The method of claim 7, where the Raman shifted light from the region passes through a Solc filter.

10. The method of claim 2, where the Raman shifted light from the region passes through a polarization-independent imaging interferometer.

11. The method of claim 10, where the Raman shifted light from the region passes through a Michelson interferometer.

12. The method of claim 10, where the Raman shifted light from the region passes through a Sagnac interferometer.

13. The method of claim 10, where the Raman shifted light from the region passes through a Twynam-Green interferometer.

14. The method of claim 10, where the Raman shifted light from the region passes through a Mach-Zehnder interferometer.

15. The method of claim 2, where the molecules are chosen from the group consisting of indoles, sulforaphanes, carotenoids, proteoglycans, and flavonoids.

16. The method of claim 15, where the molecules are carotenoid molecules.

17. The method of claim 15, where the molecules are indole molecules.

18. The method of claim 15, where the molecules are sulforphane molecules.

19. The method of claim 15, where the molecules are flavanoid molecules.

20. The method of claim 15, where the molecules are proteoglycan molecules.

21. The method of claim 2, where the region is prepared for illumination, in a step previous to step a), by excision of the tissue and by placing a specimen prepared from the tissue in position for illumination and imaging, wherein the tissue is not treated with staining agents.

22. The method of claim 2, where the region is prepared for illumination, in a step previous to step a), by excision of the tissue and by placing a specimen prepared from the tissue in position for illumination and imaging, wherein the tissue is treated with staining agents.

23. The method of claim 1, where an endoscope is introduced into the region, and the Raman shifted light signal from the molecules is detected and spatially resolved.

24. The method of claim 23, where the region is imaged using the Raman shifted light.

25. The method of claim 24, where the Raman shifted light from the region passes through a FAST fiber array spectral translator.

26. The method of claim 24, where the Raman shifted light from the region passes through a Fabry Perot tunable filter.

27. The method of claim 24, where the Raman shifted light from the region passes through an acousto-optic tunable filter.

28. The method of claim 24, where the Raman shifted light from the region passes through a liquid crystal tunable filter.

29. The method of claim 28, where the Raman shifted light from the region passes through a Lyot filter.

30. The method of claim 29, where the Raman shifted light from the region passes through an Evan'"'"'s split element liquid crystal tunable filter.

31. The method of claim 24, where the Raman shifted light from the region passes through a polarization-independent imaging interferometer.

32. The method of claim 31, where the Raman shifted light from the region passes through a Michelson interferometer.

33. The method of claim 31, where the Raman shifted light from the region passes through a Sagnac interferometer.

34. The method of claim 31, where the Raman shifted light from the region passes through a Twynam-Green Interferometer.

35. The method of claim 31, where the Raman shifted light from the region passes through a Mach-Zehnder Interferometer.

36. The method of claim 23, where the molecules are chosen from the group consisting of indoles, sulforaphanes, carotenoids, proteoglycans and flavonoids.

37. The method of claim 36, where the molecules are carotenoid molecules.

38. The method of claim 23, where a non-imaging endoscope is moved through the tissue in vivo, and the Raman shifted light signal is spatially resolved as the endoscope is moved through the tissue.

39. The method of claim 23, where the Raman shifted light from the region passes through an Evan'"'"'s split element liquid crystal tunable filter.

40. The method of claim 1, further comprising;

d) removing biopsy tissue material from a second area indicated by the first area.

41. The method of claim 40, further comprising;

e) examining the biopsy tissue material for signs of cancer.

42. The method of claim 41, further comprising;

f) excising tissue material from a third area indicated by the first area.