Low coherence interferometry for detecting and characterizing plaques

• US 7,242,480 B2
• Filed: 01/21/2005
• Issued: 07/10/2007
• Est. Priority Date: 05/14/2004
• Status: Expired due to Fees

• Current Assignee: Cardiolumen, Inc.
• Original Assignee: Medeikon Corporation
• Inventors: Alphonse, Gerard A.
• Primary Examiner(s): Lauchman; Layla G.
• Assistant Examiner(s): Lyons; Michael A.
• Application Number:
  US11/039,987
• Publication Number:
  US 20050254060A1
• Time in Patent Office: 900 Days
• Field of Search: 356/477, 356/479, 356/481, 356/497, 250/227.19, 250/227.27, 385/12
• 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 diagnosing a human condition from 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;

modulating at about a distance of a center wavelength said broadband light an effective light path length of at least one of said reference light path and said sensing light path with respect to said first depth;

detecting said broadband light resulting from said broadband light reflected from said first depth in the biological sample and said broadband light reflected from said reflecting device, to generate a first signal indicative of an interference of said broadband light reflected from said first depth in the biological sample and said broadband light reflected from said reflecting device, wherein said first signal is a product of a cosine function;

determining a first phase component that is an argument of the cosine function of the first signal;

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

modulating at about a distance of said center wavelength of said broadband light an effective light path length of at least one of said reference light path and said sensing light path with respect to said second depth;

detecting said broadband light resulting from said broadband light reflected from said second depth in the biological sample and said broadband light reflected front said reflecting device, to generate a second signal indicative of an interference of said broadband light reflected from said second depth in the biological sample and said broadband light reflected from said reflecting device, wherein said second signal is a product cosine function;

determining a second phase component that is an argument of the cosine function of the second signal;

determining a characteristic of the biological sample from said first phase component and said second phase component; and

diagnosing a human condition from the characteristic.

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 changing said effective light path lengths comprises moving said reflecting device on said reference light path.

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

5. The method of claim 2 wherein said changing 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 reflecting device is fixed.

7. The method of claim 1 wherein said modulating comprises sinusoidal modulating.

8. The method or claim 1 wherein said modulating comprises ramp modulating.

9. The method of claim 1 wherein said modulating comprises modulating excitation to metallic electrodes disposed at an optical waveguide.

10. The method of claim 1 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.

11. The method of claim 1 wherein said modulating comprises balancing said broadband light with a feed back loop.

12. 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.

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

14. The method of claim 13 wherein said determining a difference between said first phase component and said second phase component 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 component and said second phase component 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 component and said second phase component exceeds about said threshold.

15. The method of claim 1 further comprising:

determining a change in said first phase component angle of said first signal resulting from a change of said effective light path length that is itself induced by a change of a property of the biological sample; and

determining a first variation in an index of refraction from said change in the first phase component of said first signal; and

wherein said determining the characteristic of the biological sample from said first phase component and said second phase component includes determining the characteristic of the biological sample from said first variation in said index of refraction depth.

16. The method of claim 15 further comprising;

determining a change in said second phase component angle of said second signal resulting from a change of said effective light path length that is itself induced by a change of a property of the biological sample; and

determining a second variation in an index of refraction from said change in the second phase component of said second signal; and

wherein said determining the characteristic of the biological sample from said first phase component and said second phase component includes determining the characteristic of the biological sample from said second variation in said index of refraction.

17. The method of claim 16 wherein said determining the characteristic of the biological sample comprises determining a difference between said first magnitude and said second magnitude.

18. The method of claim 17 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.

19. The method of claim 1 further comprising determining a first magnitude of said first signal indicative of the interference of said broadband light reflected from said first depth in the biological sample and said broadband light reflected from said reflecting device.

20. The method of claim 19 further comprising determining a second magnitude of said second signal indicative of the interference of said broadband light reflected from said second depth in the biological sample and said broadband light reflected from said reflecting device.

21. The method of claim 19 further comprising determining the characteristic of the biological sample from said first magnitude and said second magnitude.

22. The method of claim 21 wherein said determining the characteristic of the biological sample comprises determining a difference between said first magnitude and said second magnitude.

23. The method of claim 22 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.

24. 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;

a modulator associated with at least one of said reference light path and said sensing light path, said modulator for modulating at about a distance of a center wavelength of said broadband light an effective light path length of said at least one of said reference light path and said sensing light path;

a detector receptive to said broadband light resulting from said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device, said detector generating signals indicative of an interference of said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device, which said signals are product of cosine functions;

means for changing an effective light path length of at least one of said reference light path and said sensing light path; and

a processor configured to;

(1) determine a first phase component that is an argument of the corresponding cosine function of said signal indicative of said interference of said broadband light reflected from a first depth in the biological sample and said broadband light reflected from said reflecting device based, said first depth defined by said effective light path length of said sensing light path and said effective light path length of said reference light path, (2) determine a second phase component that is an argument of the corresponding cosine function of said signal indicative of said interference of said broadband light reflected from a second depth in the biological sample and said broadband light reflected from said reflecting device based, said second depth defined by said effective light path length of at least one of said sensing light path and said reference light path having been changed, and (3) determine a characteristic of the biological sample from said first phase component and said second phase component.

25. The system of claim 24 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.

26. The system of claim 25 wherein said means for changing comprises a modulator of metallic electrodes disposed at an optical waveguide.

27. The system of claim 25 wherein said means for changing 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.

28. The system of claim 25 wherein 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.

29. The system of claim 28 wherein said modulator comprises a sinusoidal modulator.

30. The system of claim 28 wherein said modulator comprises a ramp modulator.

31. The system of claim 28 wherein said modulator comprises metallic electrodes disposed at an optical waveguide.

32. The system of claim 28 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.

33. The system of claim 28 further comprising a feedback loop associated with said modulator operating on a limit such that said broadband light resulting from interference of said broadband light reflected from the biological sample is balanced.

34. The system of claim 24 wherein said means for changing comprises a movable reflecting device disposed at said reference light path.

35. The system of claim 24 wherein said reflecting device is fixed.

36. The system of claim 24 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.

37. The system of claim 24 wherein the characteristic of the biological sample is determined based on a difference between said first phase component and said second phase component based on said first depth and said second depth.

38. The system of claim 37 wherein:

the characteristic of the biological sample is identified as within a single medium if said difference between said first phase component and said second phase component 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 component and said second phase component exceeds about said threshold.

39. The system of claim 24 wherein the characteristic of the biological sample is determined based on a difference between said first phase component and said second phase component based on a difference between said first depth and said second depth.

40. The system of claim 39 wherein:

the characteristic of the biological sample is identified lied as within a single medium if a ratio of a rate of said difference between said first phase component and said second phase component based on 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 component and said second phase component based on said difference between said first depth and said second depth exceeds about said threshold.

41. The system of claim 24 wherein said processor is further configured to:

determine a change in said first phase component of said first signal resulting from a change of said effective light path length that is itself induced by a change of a property of the biological sample;

determine a first variation in an index of refraction from said change in the first phase component of said first signal; and

determine the characteristic of the biological sample from said first variation in said index of refraction.

42. The system of claim 41 wherein said processor is further configured to:

determine a change in said second phase component of said second signal resulting from a change of said effective light path length that is itself induced by a change of a property of the biological sample;

determine a second variation in an index of refraction from said change in the second phase component of said second signal; and

determine the characteristic of the biological sample from said second variation in said index of refraction.

43. The system of claim 24 wherein said processor is further configured to determine a first magnitude of said first signal indicative of the interference of said broadband light reflected from said first depth in the biological sample said broadband light reflected from said reflecting device.

44. The system of claim 43 wherein said processor is further configured to determine a second magnitude of said second signal indicative of the interference of said broadband light reflected from said second depth in the biological sample and said broadband light reflected from said reflecting device.

45. The system of claim 44 further comprising said processor determines the characteristic of the biological sample from said first magnitude and said second magnitude.

46. The system of claim 45 wherein the characteristic of the biological sample is determined based on a difference between said first magnitude and said second magnitude.

47. The system of claim 46 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.

48. The system of claim 44 wherein the characteristic of the biological sample is determined based on a difference between said first magnitude and said second magnitude.

49. The system of claim 48 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.