Low coherence interferometry for detecting and characterizing plaques

• US 20050254061A1
• Filed: 01/21/2005
• Published: 11/17/2005
• Est. Priority Date: 05/14/2004
• Status: Active Grant

• Current Assignee: VZN Capital, LLC
• Original Assignee: Medeikon Corporation
• Inventors: Alphonse, Gerard A.
• Granted Patent: US 7,190,464 B2
• Time in Patent Office: Days
• US Class Current: 356/479
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• CPC Class Codes: A61B 5/0086 using infrared radiation
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: G01N 21/45 using interferometric methods; using Schlieren methods
• CPC Class Codes: G01N 21/474 Details of optical heads therefor, e.g. using optical fibres
• CPC Class Codes: G01N 21/4785 Standardising light scatter apparatus; Standards therefor
• CPC Class Codes: G01N 21/49 within a body or fluid

Abstract

A method and system for determining a characteristic of a biological sample including directing light at the biological sample and receiving that light; directing the light at a reference reflecting device and receiving that light; adjusting an effective light path length to facilitate an interference of the light reflected from the biological sample corresponding to a first depth and the light reflected from the reference reflecting device; and detecting the broadband light resulting from the interference, to provide an interference signal. The method also includes: determining a first phase associated with the interference signal corresponding to the first depth; varying the effective light path length to define a second depth; determining a second phase associated with the interference signal corresponding to the second depth; and determining the characteristic of the biological sample from the phases.

Claims

1. A method for determining a characteristic of a biological sample, the method comprising:

directing broadband light by means of a sensing light path at the biological sample, said sensing light path having an effective light path length;

receiving said broadband light reflected from the biological sample by means of said sensing light path;

directing said broadband light by means of a reference light path at a reference reflecting device, said reference light path having an effective light path length;

receiving said broadband light reflected from said reference reflecting device by means of said reference light path;

adjusting said effective light path length of at least one of said reference light path and said sensing light path to facilitate an interference of said broadband light reflected from the biological sample corresponding to a first depth in said biological sample and said broadband light reflected from said reference reflecting device;

detecting said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said first depth in said biological sample and said broadband light reflected from said reference reflecting device, to provide an interference signal indicative of said broadband light resulting from said interference;

determining a first phase associated with said interference signal indicative of said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said first depth in said biological sample and said broadband light reflected from said reference reflecting device;

varying said effective light path lengths of at least one of said reference light path and said sensing light path to define a second depth;

determining a second phase associated with said interference signal indicative of said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said second depth in said biological sample and said broadband light reflected from said reference reflecting device; and

determining the characteristic of the biological sample from said first phase and said second phase.

2. The method of claim 1 wherein said adjusting said effective light path length of at least one of said reference light path and said sensing light path to facilitate said interference of said broadband light reflected from the biological sample corresponding to said depth in said biological sample and said broadband light reflected from said reference reflecting device comprises:

directing said broadband light reflected from the biological sample and reflected from said reference reflecting device at a first reflecting device by means of a first light path and at a second reflecting device by means of a second light path, said first and second light paths having corresponding effective light path lengths;

combining said broadband light reflected from said first reflecting device and reflected from said second reflecting device; and

modifying said effective light path lengths of said first and second light paths to minimize a difference to within about two coherence lengths of said broadband light, said difference corresponding to the effective light path lengths of said reference light path and said sensing light path.

3. The method of claim 2 wherein at least one of said first light path and said second light path includes at least one of an optical fiber and a waveguide.

4. The method of claim 3 wherein said modifying said effective light path lengths of said first and second light paths comprises modulating excitation to metallic electrodes disposed at an optical waveguide.

5. The method of claim 3 wherein said modifying said effective light path lengths of said first and second light paths comprises modulating excitation to a piezoelectric drum having said optical fiber wound thereon forming at least a portion of at least one of said first light path and said second light path.

6. The method of claim 3 wherein said modifying said effective light path lengths of said first and second light paths comprises moving at least one of said first reflecting device on said first light path and second reflecting device on said second light path.

7. The method of claim 2 wherein at least one of said first reflecting device and said second reflecting device is fixed.

8. The method of claim 2 wherein said first depth is based on a difference between said effective light path lengths of said first light path and said second light path.

9. The method of claim 2 wherein said second depth is defined by a difference between said effective light path lengths of said first light path and said second light path.

10. The method of claim 1 wherein at least one of said reference light path and said sensing light path includes at least one of an optical fiber and a waveguide.

11. The method of claim 10 wherein said varying said effective light path lengths comprises modulating excitation to metallic electrodes disposed at an optical waveguide.

12. The method of claim 10 wherein said varying said effective light path lengths comprises modulating excitation to a piezoelectric drum having said optical fiber wound thereon forming at least a portion of at least one of said reference light path and said sensing light path.

13. The method of claim 1 wherein said varying said effective light path lengths comprises moving said reflecting device on said reference light path.

14. The method of claim 1 wherein said first depth is defined by a difference between said effective light path lengths of said reference light path and said sensing light path.

15. The method of claim 1 wherein said second depth is defined by a difference between said effective light path lengths of said reference light path and said sensing light path.

16. The method of claim 1 wherein said reflecting device is fixed.

17. The method of claim 1 wherein at least one of said determining a first phase and said determining a second phase comprises:

modulating said effective light path lengths of at least one of said reference light path and said sensing light path in accordance with a modulator function having a phase component; and

determining a magnitude of change of said effective light path lengths introduced by said modulating when said phase component of said modulator function is generally null.

18. The method of claim 17 wherein said modulator function comprises a sinusoidal modulator function.

19. The method of claim 17 wherein said modulator function comprises ramp modulator function.

20. The method of claim 17 wherein said modulating comprises modulating excitation to metallic electrodes disposed at an optical waveguide.

21. The method of claim 17 wherein said modulating comprises modulating excitation to a piezoelectric drum having said optical fiber wound thereon forming at least a portion of at least one of said reference light path and said sensing light path.

22. The method of claim 17 wherein said determining said magnitude of change of said effective light path lengths introduced by said modulating comprises balancing said broadband light resulting from interference of said broadband light reflected from the biological sample with a feed back loop.

23. The method of claim 1 further comprising calibrating at least one of said reference light path and said sensing light path by adjusting said effective light path lengths of at least one of said reference light path and said sensing light path based on a sample exhibiting known properties.

24. The method of claim 1 wherein said determining the characteristic of the biological sample comprises determining a difference between said first phase and said second phase based on said first depth and said second depth.

25. The method of claim 24 wherein said determining a difference between said first phase and said second phase based on said first depth and said second depth comprises:

identifying the characteristic of the biological sample as within a medium if said difference between said first phase and said second phase is less than about a threshold; and

identifying the characteristic of the biological sample as a boundary between mediums if said difference between said first phase and said second phase exceeds about said threshold.

26. The method of claim 1 wherein said determining the characteristic of the biological sample comprises determining a difference between said first phase and said second phase based on a difference between said first depth and said second depth.

27. The method of claim 26 wherein said determining a difference between said first phase and said second phase based on a difference between said first depth and said second depth comprises:

identifying the characteristic of the biological sample as within a medium if a ratio of a rate of said difference between said first phase and said second phase and a said difference between said first depth and said second depth is less than about a threshold; and

identifying the characteristic of the biological sample as a boundary between mediums if said ratio of said rate of said difference between said first phase and said second phase and said difference between said first depth and said second depth exceeds about said threshold.

28. The method of claim 17 further comprising determining a first variation in an index of refraction of the biological sample from said magnitude of change of said effective light path lengths and said first depth, said first variation in said index of refraction from a ratio of said magnitude of change of said effective light path length and said first depth.

29. The method of claim 27 wherein said magnitude of change of said effective light path lengths comprises one of a numerator and a denominator of said ratio and said first depth comprises an other of said numerator and said denominator of said ratio.

30. The method of claim 27 further comprising determining a second variation in an index of refraction of the biological sample from said magnitude of change of said effective light path lengths and said second depth, said second variation in said index of refraction from a ratio of said magnitude of change of said effective light path length and said second depth.

31. The method of claim 30 wherein said magnitude of change of said effective light path lengths comprises one of a numerator and a denominator of said ratio and said second depth comprises an other of said numerator and said denominator of said ratio.

32. The method of claim 1 further comprising determining a first magnitude of said broadband light resulting from said interfering based on said first depth.

34. The method of claim 32 further comprising determining the characteristic of the biological sample from said first magnitude and said second magnitude.

35. The method of claim 34 wherein said determining the characteristic of the biological sample comprises determining a difference between said first magnitude and said second magnitude based on said first depth and said second depth.

36. The method of claim 35 wherein said determining a difference between said first magnitude and said second magnitude based on said first depth and said second depth comprises:

identifying the characteristic of the biological sample as within a medium if said difference between said first magnitude and said second magnitude is less than about a threshold; and

identifying the characteristic of the biological sample as a boundary between mediums if said difference between said first magnitude and said second magnitude exceeds about said threshold.

37. The method of claim 32 wherein said determining the characteristic of the biological sample comprises determining a difference between said first magnitude and said second magnitude based on a difference between said first depth and said second depth.

38. The method of claim 36 wherein said determining a difference between said first magnitude and said second magnitude based on a difference between said first depth and said second depth comprises:

identifying the characteristic of the biological sample as within a medium if a ratio of a rate of said difference between said first magnitude and said second magnitude and a said difference between said first depth and said second depth is less than about a threshold; and

identifying the characteristic of the biological sample as a boundary between mediums if said ratio of said rate of said difference between said first magnitude and said second magnitude and said difference between said first depth and said second depth exceeds about said threshold.

33. The method of claim 33 further comprising determining a second magnitude of said broadband light resulting from said interfering based on said second depth.

39. A system for determining a characteristic of tissue in a biological sample, the system comprising:

a broadband light source for providing a broadband light;

a sensing light path receptive to said broadband light from said broadband light source, said sensing light path configured to direct said broadband light at the biological sample and to receive said broadband light reflected from the biological sample;

a reference reflecting device;

a reference light path receptive to said broadband light from said broadband light source, said reference light path configured to direct said broadband light at said reference reflecting device and to receive said broadband light reflected from said reflecting device, said reference light path coupled with said sensing light path to facilitate interference of said broadband light reflected from the biological sample and said broadband light reflected from said reference reflecting device;

means for adjusting said effective light path length of at least one of said reference light path and said sensing light path to facilitate an interference of said broadband light reflected from the biological sample corresponding to a first depth in said biological sample and said broadband light reflected from said reference reflecting device;

a detector receptive to said broadband light resulting from said interference of said broadband light reflected from the biological sample and said broadband light reflected from said reference reflecting device;

means for varying effective light path lengths of at least one of said reference light path and said sensing light path to define a second depth; and

a processor configured to;

(1) determine a first phase associated with said broadband light resulting from said interfering of said broadband light reflected from the biological sample and said broadband light reflected from said reference reflecting device based on said first depth;

(2) determine a second phase associated with said broadband light resulting from said interference of said broadband light reflected from the biological sample and said broadband light reflected from said reference reflecting device based on a second depth; and

(3) determine the characteristic of the biological sample from said first phase and said second phase.

40. The method of claim 39 wherein said means for adjusting said effective light path length of at least one of said reference light path and said sensing light path to facilitate said interference of said broadband light reflected from the biological sample corresponding to said depth in said biological sample and said broadband light reflected from said reference reflecting device comprises:

a first light path receptive to said broadband light reflected from the biological sample and reflected from said reference reflecting device, said first light path configured to direct said broadband light reflected from the biological sample and reflected from said reference reflecting device at a first reflecting device;

a second light path receptive to said broadband light reflected from the biological sample and reflected from said reference reflecting device, said second light path configured to direct said broadband light reflected from the biological sample and reflected from said reference reflecting device at a second reflecting device, said first and second light paths having corresponding effective light path lengths; and

means for modifying said effective light path lengths of said first and second light paths to minimize a difference to within about two coherence lengths of said broadband light, said difference corresponding to the effective light path lengths of said reference light path and said sensing light path.

41. The system of claim 40 wherein at least one of said first light path and said second light path includes at least one of an optical fiber and a waveguide.

42. The method of claim 41 wherein said means for modifying said effective light path lengths of said first and second light paths comprises a modulator having metallic electrodes disposed at an optical waveguide.

43. The method of claim 41 wherein said means for modifying said effective light path lengths of said first and second light paths comprises a modulator formed with a piezoelectric drum having said optical fiber wound thereon forming at least a portion of at least one of said first light path and said second light path.

44. The method of claim 41 wherein said means for modifying said effective light path lengths of said first and second light paths comprises moving at least one of said first reflecting device on said first light path and second reflecting device on said second light path.

45. The method of claim 40 wherein at least one of said first reflecting device and said second reflecting device is fixed.

46. The method of claim 40 wherein said first depth is based on a difference between said effective light path lengths of said first light path and said second light path.

47. The method of claim 40 wherein said second depth is defined by a difference between said effective light path lengths of said first light path and said second light path.

48. The system of claim 39 wherein at least one of said reference light path and said sensing light path comprises at least one of an optical fiber and a waveguide.

49. The system of claim 48 wherein said means for varying comprises a modulator of metallic electrodes disposed at an optical waveguide.

50. The system of claim 48 wherein said means for varying comprises a modulator formed with a piezoelectric drum with an optical fiber wound thereon forming at least a portion of at least one of said reference light path and said sensing light path.

51. The system of claim 39 wherein said first depth is defined by a difference between said effective light path lengths of said reference light path and said sensing light path.

52. The system of claim 39 wherein said second depth is defined by a difference between said effective light path lengths of said reference light path and said sensing light path.

53. The system of claim 39 wherein said reflecting device is fixed.

54. The system of claim 39 further including a modulator associated with at least one of said reference light path and said sensing light path, said modulator for modulating said effective light path lengths of said at least one of said reference light path and said sensing light path in accordance with a modulator function having a phase component.

55. The system of claim 54 wherein said processor is further configured to determine a magnitude of change of said effective light path length introduced by said modulator when said phase component of said modulator function is generally null for at east one of said first phase and determine said second phase.

56. The system of claim 54 wherein said modulator comprises a sinusoidal modulator.

57. The system of claim 54 wherein said modulator comprises a ramp modulator.

58. The system of claim 54 wherein said modulator comprises metallic electrodes disposed at an optical waveguide.

59. The system of claim 54 wherein said modulator comprises a piezoelectric drum with an optical fiber wound thereon forming at least a portion of at least one of said reference light path and said sensing light path.

60. The system of claim 54 further comprising a feedback loop associated with said modulator operating on a limit of said modulating such that said broadband light resulting from said interference is balanced.

61. The system of claim 39 further comprising a calibrating strip for calibrating at least one of said reference light path and said sensing light path to adjust said effective light path length of at least one of said reference light path and said sensing light path based on a sample exhibiting known properties.

62. The system of claim 39 wherein the characteristic of the biological sample is determined based on a difference between said first phase and said second phase and said first depth and said second depth.

63. The system of claim 62 wherein:

the characteristic of the biological sample is identified as within a single medium if said difference between said first phase and said second phase is less than about a threshold; and

the characteristic of the biological sample is identified as a boundary between mediums if said difference between said first phase and said second phase exceeds about said threshold.

64. The system of claim 39 wherein the characteristic of the biological sample is determined based on a difference between said first phase and said second phase and a difference between said first depth and said second depth.

65. The system of claim 64 wherein:

the characteristic of the biological sample is identified as within a single medium if a ratio of a rate of said difference between said first phase and said second phase and a difference between said first depth and said second depth is less than about a threshold; and

the characteristic of the biological sample is identified as a boundary between mediums if said ratio of said rate of said difference between said first phase and said second phase and a difference between said first depth and said second depth exceeds about said threshold.

66. The system of claim 55 further comprising said processor determines a first variation in an index of refraction of the biological sample from said magnitude of change of said effective light path lengths and said first depth, said first variation in said index of refraction comprising ratio of said magnitude of change of said effective light path lengths and said first depth.

67. The system of claim 66 wherein said magnitude of change of said effective light path lengths comprises one of a numerator and a denominator of said ratio and said first depth comprises an other of said numerator and said denominator of said ratio.

68. The system of claim 66 further comprising said processor determines a second variation in an index of refraction of the biological sample from said magnitude of change of said effective light path lengths and said second depth, said second variation in said index of refraction comprising a ratio of said magnitude of change of said effective light path lengths and said second depth.

69. The system of claim 68 wherein said magnitude of change of said effective light path lengths comprises one of a numerator and a denominator of said ratio and said first depth comprises an other of said numerator and said denominator of said ratio.

70. The system of claim 39 further comprising said processor determines a first magnitude of said broadband light resulting from said interference based on said first depth.

71. The system of claim 70 further comprising said processor determines a second magnitude of said broadband light resulting from said interference based on said second depth.

72. The system of claim 71 further comprising said processor determines the characteristic of the biological sample from said first magnitude and said second magnitude.

73. The system of claim 72 wherein the characteristic of the biological sample is determined based on a difference between said first magnitude and said second magnitude based on said first depth and said second depth.

74. The method of claim 73 wherein:

the characteristic of the biological sample is identified as within a medium if said difference between said first magnitude and said second magnitude is less than about a threshold; and

the characteristic of the biological sample is identified as a boundary between mediums if said difference between said first magnitude and said second magnitude exceeds about said threshold.

75. The system of claim 72 wherein the characteristic of the biological sample is determined based on a difference between said first magnitude and said second magnitude based on a difference between said first depth and said second depth.

76. The system of claim 75 wherein:

the characteristic of the biological sample is identified as within a medium if a ratio of a rate of said difference between said first magnitude and said second magnitude and said difference between said first depth and said second depth is less than about a threshold; and

the characteristic of the biological sample is identified as a boundary between mediums if said ratio of said rate of said difference between said first magnitude and said second magnitude and a difference between said first depth and said second depth exceeds about said threshold.

77. A system for determining a characteristic of tissue in a biological sample, the system comprising:

means for directing broadband light by means of a sensing light path at the biological sample, said sensing light path having an effective light path length;

means for receiving said broadband light reflected from the biological sample by means of said sensing light path;

means for directing said broadband light by means of a reference light path at a reference reflecting device, said reference light path having an effective light path length;

means for receiving said broadband light reflected from said reference reflecting device by means of said reference light path;

means for adjusting said effective light path length of at least one of said reference light path and said sensing light path to facilitate an interference of said broadband light reflected from the biological sample corresponding to a first depth in said biological sample and said broadband light reflected from said reference reflecting device;

means for detecting said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said first depth in said biological sample and said broadband light reflected from said reference reflecting device, to provide an interference signal indicative of said broadband light resulting from said interference;

means for determining a first phase associated with said interference signal indicative of said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said first depth in said biological sample and said broadband light reflected from said reference reflecting device;

means for varying said effective light path lengths of at least one of said reference light path and said sensing light path to define a second depth;

means for determining a second phase associated with said interference signal indicative of said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said second depth in said biological sample and said broadband light reflected from said reference reflecting device; and

means for determining the characteristic of the biological sample from said first phase and said second phase.

78. A storage medium encoded with a machine-readable computer program code for determining a characteristic of tissue in a biological sample, including instructions for causing a computer to implement a method comprising:

directing broadband light by means of a sensing light path at the biological sample, said sensing light path having an effective light path length;

receiving said broadband light reflected from the biological sample by means of said sensing light path;

directing said broadband light by means of a reference light path at a reference reflecting device, said reference light path having an effective light path length;

receiving said broadband light reflected from said reference reflecting device by means of said reference light path;

adjusting said effective light path length of at least one of said reference light path and said sensing light path to facilitate an interference of said broadband light reflected from the biological sample corresponding to a first depth in said biological sample and said broadband light reflected from said reference reflecting device;

detecting said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said first depth in said biological sample and said broadband light reflected from said reference reflecting device, to provide an interference signal indicative of said broadband light resulting from said interference;

determining a first phase associated with said interference signal indicative of said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said first depth in said biological sample and said broadband light reflected from said reference reflecting device;

varying said effective light path lengths of at least one of said reference light path and said sensing light path to define a second depth;

determining a second phase associated with said interference signal indicative of said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said second depth in said biological sample and said broadband light reflected from said reference reflecting device; and

determining the characteristic of the biological sample from said first phase and said second phase.

79. A computer data signal embodied in a computer readable format for determining a characteristic of tissue in a biological sample, the computer data signal including instructions for causing a computer to implement a method comprising:

directing broadband light by means of a sensing light path at the biological sample, said sensing light path having an effective light path length;

receiving said broadband light reflected from the biological sample by means of said sensing light path;

directing said broadband light by means of a reference light path at a reference reflecting device, said reference light path having an effective light path length;

receiving said broadband light reflected from said reference reflecting device by means of said reference light path;

adjusting said effective light path length of at least one of said reference light path and said sensing light path to facilitate an interference of said broadband light reflected from the biological sample corresponding to a first depth in said biological sample and said broadband light reflected from said reference reflecting device;

detecting said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said first depth in said biological sample and said broadband light reflected from said reference reflecting device, to provide an interference signal indicative of said broadband light resulting from said interference;

determining a first phase associated with said interference signal indicative of said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said first depth in said biological sample and said broadband light reflected from said reference reflecting device;

varying said effective light path lengths of at least one of said reference light path and said sensing light path to define a second depth;

determining a second phase associated with said interference signal indicative of said broadband light resulting from said interference of said broadband light reflected from the biological sample corresponding to said second depth in said biological sample and said broadband light reflected from said reference reflecting device; and

determining the characteristic of the biological sample from said first phase and said second phase.