Method and apparatus for determination of atherosclerotic plaque type by measurement of tissue optical properties

• US 20030028100A1
• Filed: 05/01/2002
• Published: 02/06/2003
• Est. Priority Date: 05/01/2001
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Bouma, Brett Eugene, Tearney, Guillermo J.
• Granted Patent: US 7,865,231 B2
• Time in Patent Office: Days
• US Class Current: 600/431
• CPC Class Codes: A61B 1/00165 with light-conductive means, e.g. fibre optics A61B1/07 takes precedence
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: G01B 2290/70 Using polarization in the interferometer
• CPC Class Codes: G01B 9/02007 Two or more frequencies or sources used for interferometric measurement using only beat G01B9/02003
• CPC Class Codes: G01B 9/02014 by using pulsed light
• CPC Class Codes: G01B 9/02072 by calibration or testing of interferometer
• CPC Class Codes: G01B 9/02083 characterised by particular signal processing and presentation
• CPC Class Codes: G01B 9/02088 Matching signals with a database
• CPC Class Codes: G01B 9/02091 Tomographic interferometers, e.g. based on optical coherence

Abstract

Methods for diagnosing vulnerable atherosclerotic plaque using optical coherence tomography to measure tissue optical properties, including backreflectance of heterogeneous layers, such as plaque cap, lipid pool composition and macrophage presence. Methods also include measurement of spatially and temporally dependent reflectance, measurement of multiple wavelength reflectance, low coherence interferometry, polarization and quantification of macrophage content.

Claims

1. An apparatus for characterizing atherosclerotic plaque, comprising:

a. a housing

b. a probe comprising;

i) at least one optic fiber,

ii) means for creating rotation of said fiber,

iii) at least one lens,

iv) at least one prism,

v) at least one detector,

vi) a light source;

c. means for obtaining reflectance; and

,

d. means for comparing the optical properties to a stored database of typical optical properties for a given tissue type and associated abnormalities.

2. A method for determining the thickness of a cap overlying a solid or liquid pool, comprising:

a. performing Monte Carlo simulations varying cap and lipid pool optical properties and cap thicknesses;

b. developing a lookup table of Monte Carlo results;

c. performing spatial reflectance distribution measurements for N wavelengths;

d. fitting the measured spatial reflectance distribution to known Monte Carlo simulation results (e.g., by the Levenberg-Marquardt method); and

,

e. outputting the optical properties and cap thickness from the previously computed Monte Carlo simulation that closely approximates the experimental measurements.

3. The method of claim 2, wherein the Levenberg-Marquardt method is used to fit the measured spatial reflectance distribution.

4. A method of characterizing the thickness of a cap overlying a liquid or solid pool, comprising:

a. directing a beam of light onto the surface of a sample;

b. detecting the light reflected from said surface;

c. determining the decay and broadening of said pulse reflected from said surface, said decay comprising a first curve due to the optical properties of said cap and a second curve due to the optical properties of said liquid or solid pool;

d. measuring the effective attenuation coefficient μ

_eff=1/[3μ

_s(μ

_s+μ

_a)] or the total attenuation coefficient, μ

_t=μ

_s+μ

_a, where μ

_t is the total scattering coefficient, μ

_a is the absorption coefficient, and μ

_s is the scattering coefficient;

e. measuring the thickness of said cap by determining the cutoff region where the exponential decay changes.

5. The method of claim 4, wherein said beam of light is a short temporal pulse.

6. The method of claim 4, wherein said beam of light is an oscillating beam of light in at amplitude A₁and out at amplitude A₂, where a phase shift (φ

) occurs between the two peaks and there is an amplitude decrease where A₂<

A₁.

7. A method of characterizing the thickness of a cap overlying a liquid or solid pool, comprising:

a. directing a beam of light onto the surface of a sample;

b. detecting a first wavelength of light reflected from said sample;

c. detecting a second wavelength of light reflected from said sample;

d. calculating the ratio of said first wavelength to said second wavelength; and

,

e. determining the thickness of said cap by comparing said ratio to a database of known cap thicknesses.

8. A method of characterizing the thickness of a cap overlying a liquid or solid pool, comprising:

a. identifying of the surface of the tissue at given transverse position, Θ

₀;

b. selecting a small region of interest (ROI) within the radial scan, centered at r₀, θ

₀;

c. smoothing operation over the ROI;

d. fitting the slope of the axial reflectivity within the ROI; and

,

e. mapping the slope to total attenuation coefficient and the y-intercept of the slope to corrected reflectivity for r₀, θ

₀.

9. The method of claim 8, further comprising repeating steps b.-e. for the entire image.

10. The method of claim 8, wherein said smoothing operation uses a linear filter.

11. An apparatus for imaging a sample, comprising:

a. a housing;

b. a polarized source of light;

c. a first beam splitter;

d. a reference arm;

e. a sample arm;

f. at least one interferometer;

g. at least two circulators;

h. a second beam splitter;

i. a polarizing beam splitter; and

,

j. at least two detectors.

12. A method of characterizing the thickness of a cap overlying a liquid or solid pool, comprising:

a. directing a beam of polarized light onto a sample;

b. detecting the light reflected back from said sample using at least two circulators;

c. summing the squares of the magnitude of the interference detected at said at least two circulators;

d. determining the birefringence of said sample using a combination of the signals detected by said at least two detectors.

13. The method of claim 12, wherein the relative degree of birefringence is determined by the equation:

φ

(r,θ

)=artan(<sup>A(r,θ

)</sup>/<sub>B(r,θ

)</sub>),

where (φ

(r,θ

)) is the birefringence image.

14. A method of measuring macrophage presence or content in plaque, comprising:

a. directing a beam of light onto the surface of a sample;

b. detecting the light data reflected back from said surface;

c. determining the index of refraction of said sample in a region of interest (ROI);

d. subtracting the mean background noise level from said data;

e. median filtering using a kernel in order to remove speckle noise;

f. determining the standard deviation σ

within said ROI; and

,

g. normalizing the maximum and minimum signal present in said data using the equation

$\mathrm{NSD}=\frac{\mathrm{\sigma <br><br>}}{\left(S_{\max }-S_{\min }\right)}$

where NSD is the normalized standard deviation of the OCT signal, S_max is the maximum OCT image value, and S_min is the minimum OCT image value