Low coherence interferometry for detecting and characterizing plaques

• US 20050254060A1
• Filed: 01/21/2005
• Published: 11/17/2005
• Est. Priority Date: 05/14/2004
• Status: Active Grant

• Current Assignee: Cardiolumen, Inc.
• Original Assignee: Medeikon Corporation
• Inventors: Alphonse, Gerard A.
• Granted Patent: US 7,242,480 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: A61B 5/6852 Catheters
• 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 for determining a characteristic of tissue in a biological sample comprising: directing light at the biological sample at a first depth and receiving that light reflected from the biological; directing the light at a reflecting device and receiving that light reflected from the reflecting device. The method also includes: interfering the light reflected from the biological sample and the light reflected from the reflecting device; detecting light resulting from the interfering; and determining a first phase associated with the light resulting from the interfering based on the first depth. The method further includes: varying an effective light path length to define a second depth; determining a second phase associated with the light resulting from the interfering based on the second depth; and determining the characteristic of the biological sample from the first phase and the second phase.

Claims

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

directing broadband light by means of a sensing light path at the biological sample at a first depth defined by effective light path lengths of said sensing light path and a reference light path;

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

directing said broadband light by means of said reference light path at a reflecting device;

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

interfering said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device;

detecting broadband light resulting from said interfering of said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device;

determining 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 reflecting device based on said first depth;

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 broadband light resulting from said interfering of said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device based on said second depth; and

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

2. 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.

3. The method of claim 2 wherein said varying said effective light path lengths comprises moving said reflecting device on said reference light path.

4. The method of claim 2 wherein said varying said effective light path lengths comprises modulating excitation to metallic electrodes disposed at an optical waveguide.

5. The method of claim 2 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.

6. 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.

7. 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.

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

9. 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.

10. The method of claim 9 wherein said modulator function comprises a sinusoidal modulator function.

11. The method of claim 9 wherein said modulator function comprises ramp modulator function.

12. The method of claim 9 wherein said modulating comprises modulating excitation to metallic electrodes disposed at an optical waveguide.

13. The method of claim 9 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.

14. The method of claim 9 wherein said determining a 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.

15. 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.

16. 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.

17. The method of claim 16 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.

18. 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.

19. The method of claim 18 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 a ratio 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.

20. The method of claim 9 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.

21. The method of claim 20 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.

22. The method of claim 20 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.

23. The method of claim 22 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.

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

25. The method of claim 24 further comprising determining a second magnitude of said broadband light resulting from said interfering based on said second depth.

26. The method of claim 24 further comprising determining the characteristic of the biological sample from said first magnitude and said second magnitude.

27. The method of claim 26 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.

28. The method of claim 27 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.

29. The method of claim 22 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.

30. The method of claim 29 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 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.

31. 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 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 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 fixed reflecting device;

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

means for varying effective light path lengths of at least one of said reference light path and said sensing light path; 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 reflecting device based on a first depth, said first depth defined by said effective light path lengths of said sensing light path and a reference light path, (2) determine a second 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 reflecting device based on a second depth, said second depth defined by effective light path lengths of said sensing light path and a reference light path, and (3) determine the characteristic of the biological sample from said first phase and said second phase.

32. The system of claim 31 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.

33. The system of claim 34 wherein said means for varying comprises a movable reflecting device disposed at said reference light path.

34. The system of claim 32 wherein said means for varying comprises a modulator of metallic electrodes disposed at an optical waveguide.

35. The system of claim 32 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.

36. The system of claim 31 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.

37. The system of claim 31 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.

38. The system of claim 31 wherein said reflecting device is fixed.

39. The system of claim 32 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.

40. The system of claim 39 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.

41. The system of claim 39 wherein said modulator comprises a sinusoidal modulator.

42. The system of claim 39 wherein said modulator comprises a ramp modulator.

43. The system of claim 39 wherein said modulator comprises metallic electrodes disposed at an optical waveguide

44. The system of claim 39 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.

45. The system of claim 39 further comprising a feedback loop associated with said modulator operating on a limit of said modulating such that said broadband light resulting from interference of said broadband light reflected from the biological sample is balanced.

46. The system of claim 31 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.

47. The system of claim 31 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.

48. The system of claim 47 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.

49. The system of claim 31 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.

50. The system of claim 49 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 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 phase and said second phase and said difference between said first depth and said second depth exceeds about said threshold.

51. The system of claim 40 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.

52. The system of claim 51 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.

53. The system of claim 51 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.

54. The system of claim 53 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.

55. The system of claim 31 further comprising said processor determines a first magnitude of said broadband light resulting from said interfering based on said first depth.

56. The system of claim 55 further comprising said processor determines a second magnitude of said broadband light resulting from said interfering based on said second depth.

57. The system of claim 56 further comprising said processor determines the characteristic of the biological sample from said first magnitude and said second magnitude.

58. The system of claim 57 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.

59. The system of claim 58 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.

60. The system of claim 56 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.

61. The system of claim 60 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 said difference between said first depth and said second depth exceeds about said threshold.

62. 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 at a first depth defined by effective light path lengths of said sensing light path and a reference light path;

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 said reference light path at a reflecting device;

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

means for interfering said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device;

means for detecting broadband light resulting from said interfering of said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device;

means for determining 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 reflecting device based on said first depth;

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 broadband light resulting from said interfering of said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device based on said second depth; and

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

63. 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 at a first depth defined by effective light path lengths of said sensing light path and a reference light path;

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

directing said broadband light by means of said reference light path at a reflecting device;

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

interfering said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device;

detecting broadband light resulting from said interfering of said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device;

determining 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 reflecting device based on said first depth;

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 broadband light resulting from said interfering of said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device based on said second depth; and

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

64. 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 at a first depth defined by effective light path lengths of said sensing light path and a reference light path;

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

directing said broadband light by means of said reference light path at a reflecting device;

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

interfering said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device;

detecting broadband light resulting from said interfering of said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device;

determining 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 reflecting device based on said first depth;

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 broadband light resulting from said interfering of said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device based on said second depth; and

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