Optical spectroscopy for the detection of ischemic tissue injury

• US 7,587,236 B2
• Filed: 01/08/2005
• Issued: 09/08/2009
• Est. Priority Date: 01/08/2004
• Status: Expired due to Fees

• Current Assignee: Lawrence Livermore National Security LLC (Government of the United States of America)
• Original Assignee: Lawrence Livermore National Security LLC (Government of the United States of America)
• Inventors: Troppmann, Christoph, Michalopoulou, Andromachi, Fitzgerald, Jason, Demos, Stavros
• Primary Examiner(s): Winakur; Eric F
• Assistant Examiner(s): Rozanski; Michael T
• Application Number:
  US11/031,936
• Publication Number:
  US 20050171414A1
• Time in Patent Office: 1,704 Days
• Field of Search: 600/309, 600/310, 600/322, 600/323, 600/341, 600/472, 600/476
• US Class Current: 600/477
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

An optical method and apparatus is utilized to quantify ischemic tissue and/or organ injury. Such a method and apparatus is non-invasive, non-traumatic, portable, and can make measurements in a matter of seconds. Moreover, such a method and apparatus can be realized through optical fiber probes, making it possible to take measurements of target organs deep within a patient'"'"'s body. Such a technology provides a means of detecting and quantifying tissue injury in its early stages, before it is clinically apparent and before irreversible damage has occurred.

Claims

1. A method, comprising:

illuminating a surface area of tissue with a first beam of light from a first substantially narrow spectral band source to produce an illuminated surface area, wherein said first beam of light is delivered from the distal end of an illumination transporting optic, including said distal end, wherein said distal end does not make contact with said tissue, wherein said illuminated surface area is larger than about 1.5 mm², wherein said first beam of light induces a first autofluorescence emission from said surface area;

illuminating at least part of said surface area with a second beam of light from a second substantially narrow spectral band source, wherein said second beam of light is delivered from said distal end, wherein said second beam of light induces a second autofluorescence emission from said surface area;

detecting said first autofluorescence emission and said second autofluorescense emission; and

comparing said first autofluorescence emission to said second autofluorescense emission to assess in real-time a property of said tissue.

2. The method of claim 1, wherein said first autofluorescence emission and said second autofluorescence from said tissue are within a spectral region between about 400 nm and about 1000 nm.

3. The method of claim 1, wherein said first autofluorescence emission and said second autofluorescence from said tissue are within a spectral region between about 290 nm and about 800 nm.

4. The method of claim 1, wherein said first autofluorescence emission and said second autofluorescence emission comprise an emission from a biological fluorophore.

5. The method of claim 1, wherein said first substantially narrow spectral band source and said second substantially narrow spectral band source comprise a monochromatic light source.

6. The method of claim 5, wherein said monochromatic light source can emit a wavelength of at least 250 nm.

7. The method of claim 5, wherein at least one of said first substantially narrow spectral band source and said second substantially narrow band source provides a wavelength within the absorption spectrum of NADH.

8. The method of claim 5, wherein at least one of said first substantially narrow band source and said second substantially narrow spectral band source provides a wavelength within the absorption spectrum of tryptophan.

9. The method of claim 1, wherein at least one of said first substantially narrow spectral band source and said second substantially narrow spectral band source is produced from a broad band lamp designed to transmit predetermined filtered wavelengths.

10. The method of claim 1, wherein said illumination transporting optic comprises an optical fiber bundle configured to substantially illuminate an area having a long dimension of up to about 10 cm.

11. The method of claim 10, wherein said optical fiber bundle is adapted for receiving a scattered radiation and said autofluorescence.

12. The method of claim 1, wherein the step of detecting comprises hyperspectral microscopy imaging of tissue microstructure and assessing microscopic alterations associated with tissue injury.

13. The method of claim 1, wherein said tissue is in a state of ischemia.

14. The method of claim 1, wherein said tissue is in a state of hypoxia.

15. The method of claim 1, wherein said first substantially narrow spectral band source and second substantially narrow spectral band source are polarized.

16. The method of claim 1, wherein said first substantially narrow spectral band source and second substantially narrow spectral band source are linearly polarized and a parallel-polarized component of at least one of said first autofluorescence emission or said second autofluorescence emission is analyzed.

17. The method of claim 16, wherein a perpendicularly polarized component of at least one of said first autofluorescence emission or said second autofluorescence emission is analyzed.

18. The method of claim 1., wherein one of said first autofluorescence emission or said second autofluorescence emission comprises an opposite circular polarization orientation with respect to said first substantially narrow spectral band source and said second substantially narrow spectral band source, said method further comprising analyzing said opposite circular polarization orientation.

19. The method of claim 1, wherein said first substantially narrow spectral band source and said second substantially narrow spectral band source are elliptically polarized and a same elliptical polarization orientation of said first autofluorescence emission and said second au tofluorescence emission is analyzed.

20. The method of claim 19, wherein an orthogonal elliptical polarization of at least one of said first autofluorescence emission or said second autofluorescence is analyzed.

21. The method of claim 1, wherein said first substantially narrow spectral band source and said second substantially narrow spectral band source are polarized and a scattered electromagnetic radiation is analyzed.

22. The method of claim 21, wherein an orthogonal polarization component of said scattered electromagnetic radiation is analyzed.

23. The method of claim 1, wherein the detecting step is carried out with a charge coupled device.

24. The method of claim 1, wherein the detecting step is carried out with a device selected from the group consisting of a photomultiplier and a photodiode.

25. The method of claim 1, wherein said tissue is selected from the group consisting of brain, kidney, liver, heart, bowel, skin, stomach, pancreas, and muscle.

26. The method of claim 1, further comprising infusing a fluorescing contrast agent into said tissue to determine a quantifiable measurement of tissue injury.

27. An apparatus for assessing tissue parameters, comprising:

a first source of electromagnetic radiation configured to produce a first beam of light having a substantially narrow spectral band;

a second source of electromagnetic radiation configured to produce a second beam of light having a substantially narrow spectral band;

an illumination transporting optic, comprising a distal end, wherein said conduit is adapted for directing said first beam of light and said second beam of light to illuminate from said distal end, a surface area of a tissue to produce an illuminated surface area, wherein said illuminated surface area is larger than about 1.5 mm², wherein said first beam of light induces a first autofluorescence emission from said surface area and wherein said second beam of light induces a second autofluorescence emission, wherein said conduit further comprises means for receiving and directing said first autofluorescence emission and said second autofluorescence emission;

a spacer fixedly attached to said distal end to place said distal end in a position that is not touching said tissue;

a device adapted to record said first autofluorescence emission and said second au tofluorescence emission; and

means for comparing said first autofluorescence emission and said second autofluorescence emission to assess in real-time a property of said tissue.

28. The apparatus of claim 27, wherein said first substantially narrow band and said second substantially narrow spectral band source comprise a laser that can emit a wavelength of at least 250 nm.

29. The apparatus of claim 27, wherein said laser is a commercially available compact laser.

30. The apparatus of claim 29, wherein said compact laser comprises a laser diode.

31. The apparatus of claim 27, wherein at least one of said first substantially narrow spectral band source and said second substantially narrow spectral band source are produced from a broad band optical lamp designed to transmit predetermined filtered wavelengths.

32. The apparatus of claim 27, wherein said first autofluorescence emission and said second autofluorescence from said tissue are within a spectral band between about 400 nm and about 1000 nm.

33. The apparatus of claim 27, wherein said first autofluorescence emission and said second autofluorescence from said tissue are within a spectral band between about 290 nm and about 800 nm.

34. The apparatus of claim 27, wherein said first autofluorescence emission and said second autofluorescence comprise an emission from a biological fluorophore.

35. The apparatus of claim 27, wherein at least one of said first substantially narrow spectral band source and said second substantially narrow band source provides a wavelength within the absorption spectrum of NADH.

36. The apparatus of claim 27, wherein at least one of said first substantially narrow spectral source and said second substantially narrow band source provides a wavelength within the absorption spectrum of tryptophan.

37. The apparatus of claim 27, further comprising means for hyperspectral microscopy to image tissue microstructure and assess microscopic alterations associated with injury of said tissue.

38. The apparatus of claim 27, wherein said tissue is in a state of ischernia.

39. The apparatus of claim 27, wherein said tissue is in a state of hypoxia.

40. The apparatus of claim. 27, wherein said first beam and said second beam comprise polarized light.

41. The apparatus of claim 27, wherein said first beam and said second beam are linearly polarized and a parallel-polarized component of at least one of said first autofluorescence emission -and said second autofluorescence emission is analyzed.

42. The apparatus of claim 41, wherein a perpendicularly polarized component of said first autofluorescence emission and said second autofluorescence emission is analyzed.

43. The apparatus of claim 27, wherein one of said first autofluorescence emission or said second autofluorescence emission comprises an opposite circular polarization orientation with respect to at least one of said first beam or said second beam, wherein said apparatus further comprises means for analyzing said opposite circular polarization orientation.

44. The apparatus of claim 27, wherein at least one of said first beam and said second beam comprises an elliptically polarized orientation, wherein said apparatus further comprises means for analyzing said elliptically polarized orientation.

45. The apparatus of claim 44, wherein at least one of said first beam or said second beam comprise an orthogonal elliptical polarization orientation, wherein said apparatus further comprises means for analyzing said orthogonal elliptical polarization orientation.

46. The apparatus of claim 27, wherein at least one of said first beam and said second beam is polarized and produces scattered electromagnetic radiation, wherein said apparatus further comprises means for analyzing said scattered electromagnetic radiation.

47. The apparatus of claim 46, wherein said scattered electromagnetic radiation comprises an orthogonal polarization component, wherein said apparatus further comprises means for analyzing said orthogonal polarization component.

48. The apparatus of claim 27, wherein said device comprises a charge coupled device.

49. The apparatus of claim 27, wherein said device comprises at least one detector selected from the group consisting of a photomultiplier and a photodiode.

50. The apparatus of claim 27, wherein said tissue is selected from the group consisting of brain, kidney, liver, heart, bowel, stomach, skin, pancreas, and muscle.

51. The apparatus of claim 27, wherein said conduit comprises an optical fiber bundle.

52. The apparatus of claim 51, wherein said fiber bundle comprises at least one illumination fiber having a diameter between about 500 microns and about 1 mm.

53. The apparatus of claim 52, wherein said illumination transporting optic is arranged to illuminate said tissue in a long dimension of up to about 10 cm.

54. The apparatus of claim 51, wherein said means for receiving and directing comprises one or more optical fibers having distal ends fixedly positioned adjacent to said distal end of said illumination transporting optic.