Methods and apparatus for in vivo identification and characterization of vulnerable atherosclerotic plaques

• US 6,816,743 B2
• Filed: 01/24/2001
• Issued: 11/09/2004
• Est. Priority Date: 10/08/1998
• Status: Expired due to Term

• Current Assignee: University Of Kentucky Research Foundation (University of Kentucky)
• Original Assignee: University Of Kentucky Research Foundation (University of Kentucky)
• Inventors: Lodder, Robert A., Muller, James E., Moreno, Pedro, OʼConnor, William
• Primary Examiner(s): Lateef, Marvin M.
• Assistant Examiner(s): Lin, Jeoyuh
• Application Number:
  US09/768,920
• Publication Number:
  US 20010047137A1
• Time in Patent Office: 1,385 Days
• Field of Search: 600/473, 600/476, 600/478, 600/479, 600/477, 600/306, 250/338.1, 250/339.01, 250/339.05, 250/339.11, 250/340, 250/341.1, 250/341.8, 382/128, 382/130
• US Class Current: 600/473
• CPC Class Codes: A61B 2017/22001 Angioplasty, e.g. PCTA
• 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

Abstract

Methods and apparatus for analyzing the chemical composition of vulnerable plaques with an intravascular catheter having a near-infrared light source, a fiber-optic probe, a mechanism for directing the light from the light source into a blood vessel, and detectors for detecting light reflected or scattered by the tissue. The light source may be a tunable laser, and may transmit an incident beam having a wavelength ranging from 1400 to 4100 nm. A computer may be included to receive and process the spectral data in the analysis of the vulnerable plaques. A catheter system may be configured to provide near-IR spectrometric imaging of arteries to non-destructively locate and determine lipid pool and fibrous cap size and composition. Additionally, mediators and cellular components may be also determined that are typically associated with vulnerable plaques which have an increased risk of rupture. The lipid pool, fibrous cap, and inflammatory response may serve as an in vivo marker for vulnerable atherosclerotic plaques. Methods are further provided for prospectively identifying and characterizing vulnerable plaques which may include the steps of focusing near-IR light onto a blood vessel wall; detecting the scattered light in the region; and analyzing the resulting spectra across the full preselected wavelength range, particularly in the ranges that include identifying peaks for vulnerable plaque constituents.

Claims

1. A method for detecting a fibrous cap in a blood vessel wall, the method comprising

(a) illuminating the blood vessel wall with near-infrared light at a range of wavelengths from about 1200 to 2400 nm;

(b) detecting light reflected from the blood vessel wall having a range of wavelengths from about 1200 to 2400 nm to obtain a sample reflectance spectrum; and

(c) comparing the sample reflectance spectrum to a known reflectance spectrum of a fibrous cap as set forth in FIG. 3, wherein a sample reflectance spectrum that substantially matches the known reflectance spectrum of a fibrous cap indicates the presence of a fibrous cap in the blood vessel wall.

2. The method of claim 1, wherein the comparing is done using analytical software.

3. The method of claim 1, wherein the comparing is done using pattern recognition software.

4. The method of claim 1, wherein the sample spectrum is normalized by subtraction of a mean absorbance at each wavelength at each pixel to obtain a subtraction spectrum, and dividing the subtraction spectrum by a standard deviation of absorbances of each wavelength.

5. The method of claim 1, wherein the blood vessel wall is in vivo.

6. The method of claim 1, wherein the blood vessel is an artery.

7. The method of claim 1, wherein the blood vessel is a coronary artery.

9. A method for detecting cholesterol in a blood vessel wall, the method comprising

(a) illuminating the blood vessel wall with near-infrared light at a range of wavelengths from about 1200 to 2400 nm;

(b) detecting light reflected from the blood vessel wall having a range of wavelengths from about 1200 to 2400 nm to obtain a sample reflectance spectrum; and

(c) comparing the sample reflectance spectrum to a known reflectance spectrum of cholesterol as set forth in FIG. 1, wherein a sample reflectance spectrum that substantially matches the known reflectance spectrum of cholesterol indicates the presence of cholesterol in the blood vessel wall.

10. The method of claim 9, wherein the blood vessel is a coronary artery.

11. A method for detecting lysophosphatidylcholine (LPC) in a blood vessel wall, the method comprising

(a) illuminating the blood vessel wall with near-infrared light at a range of wavelengths from about 1200 to 2400 nm;

(b) detecting light reflected from the blood vessel wall having a range of wavelengths from about 1200 to 2400 nm to obtain a sample reflectance spectrum; and

(c) comparing the sample reflectance spectrum to a known reflectance spectrum of LPC as set forth in FIG. 2, wherein a sample reflectance spectrum that substantially matches the known reflectance spectrum of LPC indicates the presence of LPC in the blood vessel wall.

8. A method of detecting a vulnerable plaque in a blood vessel wall, the method comprising

locating a fibrous cap in a blood vessel wall by the method of claim 11; and

determining the thickness of the fibrous cap based on the sample reflectance spectrum, wherein the presence of a fibrous cap that is less than 65 microns in thickness indicates that the blood vessel wall contains a vulnerable plaque.

12. The method of claim 11, wherein the blood vessel is a coronary artery.

13. A method for detecting a lipid pool in a blood vessel wall, the method comprising

(a) illuminating the blood vessel wall with near-infrared light at a range of wavelengths from about 1200 to 2400 nm;

(b) detecting light reflected from the blood vessel wall having a range of wavelengths from about 1200 to 2400 nm to obtain a sample reflectance spectrum; and

(c) comparing the sample reflectance spectrum to a known reflectance spectrum of a lipid pool as set forth in FIG. 12, wherein a sample reflectance spectrum that substantially matches the known reflectance spectrum of a lipid pool indicates the presence of a lipid pool in the blood vessel wall.

14. The method of claim 13, wherein the blood vessel is a coronary artery.

15. A method of determining whether a plaque containing a lipid pool in a blood vessel wall is vulnerable to rupture, the method comprising

locating a lipid pool in a blood vessel wall by the method of claim 13; and

determining the cross-sectional area of the lipid pool as a percentage of a total cross-sectional area of a plaque associated with the lipid pool;

wherein a lipid pool greater than 30 percent of the total plaque indicates that the plaque is vulnerable to rupture.