Catheter based mid-infrared reflectance and reflectance generated absorption spectroscopy

• US 8,571,640 B2
• Filed: 12/10/2004
• Issued: 10/29/2013
• Est. Priority Date: 12/11/2003
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Holman, Hoi-Ying N
• Primary Examiner(s): Chen, Tse
• Assistant Examiner(s): Brutus, Joel F
• Application Number:
  US10/582,422
• Publication Number:
  US 20070078348A1
• Time in Patent Office: 3,245 Days
• Field of Search: 600/476, 600/433, 600/473, 600/434, 600/462, 600/466, 600/467
• US Class Current: 600/476
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• 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 5/0086 using infrared radiation
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/7257 using Fourier transforms
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence

Abstract

A method of characterizing conditions in a tissue, by (a) providing a catheter that has a light source that emits light in selected wavenumbers within the range of mid-IR spectrum; (b) directing the light from the catheter to an area of tissue at a location inside a blood vessel of a subject; (c) collecting light reflected from the location and generating a reflectance spectra; and (d) comparing the reflectance spectra to a reference spectra of normal tissue, whereby a location having an increased number of absorbance peaks at said selected wavenumbers indicates a tissue inside the blood vessel containing a physiological marker for atherosclerosis.

Claims

1. A method of characterizing subsurface conditions in a tissue, comprising (a) providing a catheter that has a light source that emits light in selected wavenumbers within the range of mid-infrared (IR) spectrum;

(b) emitting light in said selected wavenumbers within the range of mid-IR spectrum and directing the light in said selected wavenumbers within the range of mid-IR spectrum from the catheter to an area of tissue at a subsurface location at or below the tunica intima of a blood vessel of a subject;

(c) collecting light reflected from the subsurface location and generating a reflectance spectra; and

(d) comparing said reflectance spectra to a reference spectra of normal tissue, whereby a subsurface location having an increased number of absorbance peaks at said selected wavenumbers indicates a subsurface tissue inside said blood vessel containing a physiological marker for atherosclerosis, wherein the comparing step comprises that increased numbers of absorbance peaks at said selected wavenumbers are within at least one range of mid-infrared wavenumbers selected from the group of;

about 3800-3000 cm<sup>−

1</sup>, about 3500-3000 cm<sup>−

1</sup>, and about 3020-3000 cm<sup>−

1</sup>.

2. The method of claim 1 wherein the comparing step comprises that increased numbers of absorbance peaks at said selected wavenumbers are in the range between about 3000-3100 cm⁻

1.

3. The method of claim 1, further comprising the step of generating a spatially resolved map of reflectance generated spectral signals from different locations within a single vessel.

4. A method of characterizing conditions in a subsurface tissue, comprising (a) providing a catheter that has a light source that emits light in selected wavenumbers within the range of mid-infrared (IR) spectrum;

(b) emitting light in in said selected wavenumbers within the range of mid-IR spectrum and directing the light in said selected wavenumbers within the range of mid-IR spectrum from the catheter to an area of tissue at a subsurface tissue location in or below the tunica intima of a blood vessel of a subject;

(c) collecting light reflected from the subsurface tissue location and generating a reflectance spectra; and

(d) comparing said reflectance spectra to a reference spectra of normal tissue, whereby a location having an increased number of absorbance peaks at said selected wavenumbers indicates a subsurface tissue in or below the tunica intima of said blood vessel containing a physiological marker for atherosclerosis, wherein the comparing step comprises that increased numbers of absorbance peaks at said selected wavenumbers is in the range of wavenumbers 4000 to 400 cm<sup>−

1</sup>, wherein at least one peak is at about 3300 cm<sup>−

1</sup>, or about 3005 cm<sup>−

1</sup>.

5. An apparatus for characterizing subsurface tissue conditions, comprising:

(a) a single or multiple source of mid-IR light covering a range of mid-infrared wavenumbers;

(b) a catheter coupled to said source and a detector to detect light reflected by subsurface tissue in or below the tunica intima of a blood vessel of a subject;

(c) a computer means for generating the reflectance generated spectra at selected wavenumbers detected by said detectors and containing the generated spectra to a reference reflectance spectra of normal tissue, to determine whether the subject has atherosclerosis, wherein the selected wavenumbers are about 3800-3000 cm<sup>−

1</sup>, about 3500-3000 cm<sup>−

1</sup>, and about 3020-3000 cm<sup>−

1</sup> and wherein said computer means has stored therein the reference wavenumber range of 4000-400 cm<sup>−

1</sup>.

6. The apparatus of claim 5, wherein said computer means has stored therein at least one of the following reference wavenumber ranges, expressed in cm⁻

1;

about 4000-2800, about 3500-3000, about 3020-3000, about 2950-2800, about 1760-1710, about 1690-1610, about 1520-1500, about 1480-1450, and about 1100-900 and about 900-400.

7. The apparatus of claim 6, wherein said computer means has stored therein at least one of the following reference wavenumber ranges, expressed in cm⁻

1;

about 3500-3000, about 3020-3000, and about 1520-1500.

8. The apparatus of claim 5, further comprising an interferometer.

9. The apparatus of claim 5, wherein said catheter comprises a source fiber and a detection fiber having a tip or a tip array, wherein the tip is configured for detecting reflectance generated spectra.

10. The apparatus of claim 5, further comprising a tuning system for said source.

11. The apparatus of claim 5, further comprising a cooling means for said detector.

12. The apparatus of claim 11, further comprising the additional use of customized bandwidth and special gain for DC- and/or AC-coupled preamps for the detectors to increase the signal-to-noise ratio of the detectors.

13. A method of characterizing atherosclerosis in the subsurface of a biological material that has enhanced reflectance and/or spectral features, comprising the steps of:

(a) providing light in selected mid-IR wavenumbers between about 4000 to about 400 cm<sup>−

1</sup>;

(b) directing the light through a probe to a subsurface area in or below the tunica intima of said biological material;

(c) measuring reflected light returning through the probe over a range of selected wavenumbers to generate a pattern of spectral signals representative of said area; and

(d) comparing spectral signals from a reference spectra to the spectral signals from said area for enhanced reflectance and/or spectral features, wherein said range of selected wavenumbers is selected from the group of;

about 3800-3000 cm<sup>−

1</sup>, about 3500-3000 cm<sup>−

1</sup>, about 3020-3000 cm<sup>−

1</sup> wherein enhanced reflectance and/or spectral features at the selected wavenumbers characterizes said area of said biological material as atherosclerotic.

14. A method of spectroscopic diagnosis of tissue comprising:

irradiating a subsurface portion of tissue at a target area at or below the tunica intima in the blood vessel of a subject with radiation having a frequency within the mid-infrared range, transmitted through a fiber optic cable;

detecting light reflected by the subsurface area of tissue in or below the tunica intima response to the radiation, the light having a range of 4000 cm<sup>−

1</sup> to 400 cm<sup>−

1</sup>; and

analyzing the detected reflectance light to diagnose whether the tissue is atherosclerotic including the step of comparing the detected light with reference data, wherein said detected reflectance light is analyzed in at least one of the following wavenumber ranges;

about 3800-3000 cm<sup>−

1</sup>, about 3500-3000 cm<sup>−

1</sup>, and about 3020-3000 cm<sup>−

1</sup>.

15. The method of claim 14, wherein the detecting step further comprises collecting the reflected light through the fiber optic cable.

16. The method of claim 14, wherein the irradiation step further comprises a catheter means for insertion of the fiber optic cable in body lumens.

17. The method of claim 14, wherein the fiber optic cable receives light reflected by the tissue and transmits the reflected light to a spectroscopic analysis system.

18. The method of claim 14, further comprising an alternate spectrophotometer to receive the reflected light.

19. The method of claim 14, further comprising the step of rotating the fiber optic cable radially within the blood vessel, whereby data is acquired at various target locations radially within the lumen.

20. The method of claim 19, wherein the steps are repeated thereby performing a 360-degree spectral analysis of the body lumens.

21. A method of detecting vulnerable plaques in a blood vessel tissue of a subject comprising the steps of:

delivering mid-infrared light to a subsurface tissue to be diagnosed, irradiating said blood vessel tissue with said light, detecting any delivered light reflected by any vulnerable plaque within the same range as the mid-infrared delivered light, and determining the chemical composition and cellular conditions in the subsurface tissue that indicate vulnerable plaque in a blood vessel in or below the tunica intima, wherein the reflected light is detected in at least one of the following wavenumber ranges;

about 3800-3000 cm<sup>−

1</sup>, about 3500-3000 cm<sup>−

1</sup> and about 3020-3000 cm<sup>−

1</sup>.