SYSTEMS AND METHODS FOR SPECTRAL ANALYSIS OF A TISSUE MASS USING AN INSTRUMENT, AN OPTICAL PROBE, AND A MONTE CARLO OR A DIFFUSION ALGORITHM

• US 20110112435A1
• Filed: 09/29/2008
• Published: 05/12/2011
• Est. Priority Date: 09/28/2007
• Status: Active Grant

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Yu, Bing, Brown, Jonathon Quincy, Ramanujam, Nirmala
• Granted Patent: US 9,820,655 B2
• Time in Patent Office: Days
• US Class Current: 600/567
• 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 5/0086 using infrared radiation
• CPC Class Codes: A61B 5/0091 for mammography
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant
• CPC Class Codes: A61B 5/4312 Breast evaluation or disorder diagnosis A61B5/0091 takes precedence

Abstract

Systems and methods for spectral analysis of a tissue mass using an instrument, an optical probe, and a Monte Carlo algorithm or a diffusion algorithm are provided. According to one method, an instrument is inserted into a tissue mass. A fiber optic probe is applied via the instrument into the tissue mass. Turbid spectral data of the tissue mass is measured using the fiber probe. The turbid spectral data is converted to absorption, scattering, and/or intrinsic fluorescence spectral data via a Monte Carlo algorithm or diffusion algorithm. Biomarker concentrations in the tissue mass are quantified using the absorption, scattering, and/or intrinsic fluorescence spectral data.

Claims

1. A system for determining biomarker concentrations in a tissue mass, the system comprising:

an instrument for inserting into the tissue mass;

a fiber optic probe for interfacing the tissue mass via the instrument and measuring turbid spectral data of the tissue mass; and

a processing unit for converting the turbid spectral data to at least one of absorption, scattering, and intrinsic fluorescence spectral data via a Monte Carlo algorithm or a diffusion algorithm and quantifying biomarker concentrations in the tissue mass using the absorption, scattering, and intrinsic fluorescence spectral data.

2. The system of claim 1 wherein the fiber optic probe comprises at least one of a forward firing fiber optic probe and a side firing fiber optic probe.

3. The system of claim 2 wherein the fiber optic probe is adapted to fit within a biopsy needle or a biopsy cannula.

4. The system of claim 3 wherein the biopsy needle includes at least one of a Suros 9 G biopsy needle, a Mammotome biopsy needle, a Bard Vacora 10 G biopsy needle, a Bard Vacora 14 G biopsy needle, and a Cardinal Achieve 14 G biopsy needle.

6. The system of claim 1 wherein the instrument comprises a cannula, a biopsy needle, an endoscopic instrument, and a laparoscopic instrument.

8. The system of claim 1 wherein the turbid spectral data comprises diffuse reflectance spectral data and fluorescence spectral data of the tissue mass.

9. The system of claim 1 wherein the biomarker concentrations are used to determine if the tissue mass is malignant, benign, or normal, or are used to quantify drug uptake by the tissue mass.

10. The system of claim 9 wherein a biopsy is conducted on the tissue mass through a cannula or a biopsy needle if the tissue is malignant.

12. The system of claim 1 wherein the fiber optic probe is adapted to acquire the turbid spectral data using a spectrometer having a spectral bandpass of between about 2.5 nm and 5 nm.

13. The system of claim 1 wherein the Monte Carlo algorithm includes either an inverse Monte Carlo reflectance algorithm or an inverse Monte Carlo fluorescence algorithm.

14. The system of claim 1 wherein the fiber optic probe includes a side firing fiber optic probe adapted for interfacing the tissue mass and measuring turbid spectral data of the tissue mass, and wherein the side firing fiber optic probe comprises a one-end-sealed stainless steel tube with a side facing aperture, two side firing illumination fibers, and a side firing collection fiber, forming two source-detector separations.

18. The system of claim 14 wherein each of the side firing fibers includes an angled fiber tip that includes a reflective coating, an absorptive coating on its outer surface for blocking light leaks directly from illumination fibers or scattered lights inside the stainless steel tube, or both.

20. The system of claim 18 wherein biocompatible epoxy is used for sealing the side facing aperture and for index-matching material between the fiber tips and the tissue mass.

25. The system of claim 1 wherein the processing unit is further configured to determine the concentrations at least one of total hemoglobin, oxyhemoglobin concentration, deoxyhemoglobin concentration, beta carotene concentration, hemoglobin saturation, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), collagen, porphyrins, retinol, tryptophan, tissue blood loss, dilutional effects of fluids, in vivo.

26. The system of claim 1 wherein the fiber optic probe includes a forward firing fiber optic probe adapted for interfacing the tissue mass and measuring turbid spectral data of the tissue mass, and wherein the forward firing fiber optic probe includes a probe tip comprised of a plurality of fibers.

27. The system of claim 26 wherein the plurality of fibers in the forward firing fiber optic probe are configured with a central core of illumination fibers surrounded by a single concentric ring of collection fibers or a plurality of concentric rings of collection fibers, wherein each concentric ring includes a plurality of ring-specific collection fibers.

5. (canceled)

7. (canceled)

11. (canceled)

15-17. -17. (canceled)

19. (canceled)

21-24. -24. (canceled)

28-31. -31. (canceled)

32. A method for determining biomarker concentrations in a tissue mass, the method comprising:

inserting an instrument into the tissue mass; and

applying a fiber optic probe via the instrument into the tissue mass;

measuring turbid spectral data of the tissue mass using the fiber optic probe;

converting the turbid spectral data to at least one of absorption, scattering, and intrinsic fluorescence spectral data via a Monte Carlo algorithm or a diffusion algorithm; and

quantifying biomarker concentrations in the tissue mass using the at least one of absorption, scattering, and intrinsic fluorescence spectral data.

33. The method of claim 32 wherein the fiber optic probe comprises at least one of a forward firing fiber optic probe and a side firing fiber optic probe.

34. The method of claim 33 wherein the fiber optic probe is adapted to fit within a biopsy needle or a biopsy cannula.

36. The method of claim 34 wherein the biopsy needle includes at least one of a Suros 9 G biopsy needle, a Mammotome biopsy needle, a Bard Vacora 10 G biopsy needle, a Bard Vacora 14 G biopsy needle, and a Cardinal Achieve 14 G biopsy needle.

37. The method of claim 32 wherein the instrument comprises a cannula, a biopsy needle, an endoscopic instrument, and a laparoscopic instrument.

39. The method of claim 32 wherein the turbid spectral data comprises diffuse reflectance spectral data and fluorescence spectral data of the tissue mass.

40. The method of claim 32 wherein the biomarker concentrations are used to determine if the tissue mass is malignant, benign, or normal, or are used to quantify drug uptake by the tissue mass.

41. The method of claim 40 wherein a biopsy is conducted on the tissue mass through a cannula or a biopsy needle if the tissue is malignant.

43. The method of claim 32 wherein the fiber optic probe is adapted to acquire the turbid spectral data using a spectrometer having a spectral bandpass of between about 2.5 nm and 5 nm.

44. The method of claim 32 wherein the Monte Carlo algorithm includes either an inverse Monte Carlo reflectance algorithm or an inverse Monte Carlo fluorescence algorithm.

45. The method of claim 32 wherein the fiber optic probe includes a side firing fiber optic probe adapted for interfacing the tissue mass and measuring turbid spectral data of the tissue mass, and wherein the side firing fiber optic probe comprises a one-end-sealed stainless steel tube with a side facing aperture, two side firing illumination fibers, and a side firing collection fiber, forming two source-detector separations.

49. The method of claim 45 wherein each of the side firing fibers includes an angled fiber tip that includes a reflective coating, an absorptive coating on its outer surface for blocking light leaks directly from illumination fibers or scattered lights inside the stainless steel tube, or both.

51. The method of claim 49 wherein biocompatible epoxy is used for sealing the side facing aperture and for index-matching material between the fiber tips and the tissue mass.

52. The method of claim 32 further comprising:

applying a contrast agent to the tissue mass to enhance light scattering, absorption, or fluorescence in the tissue mass.

53. The method of claim 52 wherein the enhanced light scattering, absorption, or fluorescence aids with margin assessment.

54. The method of claim 52 wherein the contrast agent includes at least one of acetic acid, Acriflavin, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (NBDG), fluorescin, aminolevulinic acid, and methlyene blue.

55. The method of claim 32 wherein the processing unit is further configured to determine the concentrations at least one of total hemoglobin, oxyhemoglobin concentration, deoxyhemoglobin concentration, beta carotene concentration, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), collagen, retinol, porphyrin, hemoglobin saturation, tissue blood loss, dilutional effects of fluids in vivo.

56. The method of claim 32 wherein the fiber optic probe includes a forward firing fiber optic probe adapted for interfacing the tissue mass and measuring turbid spectral data of the tissue mass, and wherein the forward firing fiber optic probe includes a probe tip comprised of a plurality of fibers.

57. The method of claim 56 wherein the plurality of fibers in the forward firing fiber optic probe are configured with a central core of illumination fibers surrounded by a single concentric ring of collection fibers or a plurality of concentric rings of collection fibers, wherein each concentric ring includes a plurality of ring-specific collection fibers.

35. (canceled)

38. (canceled)

42. (canceled)

46-48. -48. (canceled)

50. (canceled)

58-61. -61. (canceled)

62. A system for determining biomarker concentrations in a tissue mass, the system comprising:

a side firing fiber optic probe for inserting into a tissue mass and measuring turbid spectral data of the tissue mass, wherein the side firing fiber optic probe includes a one-end-sealed stainless steel tube with a side facing aperture, two side firing illumination fibers, and a side firing collection fiber, forming two-source detector separations, wherein the sealed end of the stainless steel tube includes a sharpened point adapted for insertion into the tissue mass; and

a processing unit for converting the turbid spectral data to at least one of absorption and scattering spectral data via a diffusion algorithm and quantifying biomarker concentrations in the tissue mass using the absorption and scattering spectral data.