Abstract#116122: American Heart Association Scientific Sessions

2001

PROGRESS WITH THE CALIBRATION OF A 3F NEAR INFRARED SPECTROSCOPY FIBER OPTIC CATHETER

FOR MONITORING THE pH OF ATHEROSCLEROTIC PLAQUE:

INTRODUCING A NOVEL APPROACH FOR THE DETECTION OF VULNERABLE PLAQUE

Tania Khan, Babs Soller, Mohammad Madjid, James T. Willerson, S. Ward Casscells, Morteza Naghavi

Texas Heart Institute

Everybody has atherosclerosis, the question is who has vulnerable plaque

Sudden Cardiac DeathAcute MI

VulnerablePlaque(s)

Morphology vs. Activity Imaging

Inactive and non-inflamed plaque

Active and inflamed

plaque Appear Similar in

IVUS OCT MRI w/o CM

Morphology

Show Different

Activity

Thermography, Spectroscopy, immunoscientigraphy, MRI with

targeted contrast media…

- Raman Spectroscopy

- Near-Infrared Diffuse Reflectance Spectroscopy

-Fibrousis and lipid measurement

-pH and lactate measurement

- Fluorescence Emission Spectroscopy

- Spectroscopy with contrast media

Intravascular Near Infrared Spectroscopy

Intra-coronary assessment of endothelial function

Intra-coronary measurement of MMPs and cytokines

Long-Term Objectives

• Determine a empirical calibration for plaque pH using a spectroscopic fiber optic catheter system

• Identify metabolic status of atherosclerotic plaques• Locate and identify vulnerable plaque with Near

Infrared Spectroscopy

Previous Work

• Near-infrared (NIR) spectroscopy has been proposed by both Lodder (UKY) and Feld (MIT) to characterize properties of vulnerable atherosclerotic plaques (VP) such as thin cap and large lipid core.

• Inflamed regions of plaque are lower in pH in the atherosclerotic Watanabe rabbit; plaque pH heterogeneity demonstrated (Grascu, 1999)

• Tissue pH can be measured by NIR spectroscopy in heart muscle (Soller, Zhang 1998)

NIR Spectroscopy• Visible to near infrared light

delivered and collected by optical catheter detect changes in broad, overlapping absorption bands in proteins, lipoproteins, water, etc.

• Different pathological plaques have different optical spectra

H&E staining of biopsies taken of same area spectra taken. From left to right: 1. Thrombus, 2. Fibrous, and 3. Calcified.

1.0

1.5

2.0

2.5

3.0

3.5

4.0

400 500 600 700 800 900 1000 1100wavelength

abso

rban

ce (a

.u.)

Calcified

Thrombus

Fibrous

Hypothesis

A feasible optical spectroscopic method for measuring tissue pH in ex-vivo human carotid plaques can be achieved with a localized fiber optic catheter.

Optical Catheter System Diagram

• Optical fibers carry light to tissue• Light is reflected and/or backscattered

toward fibers that return light to detector and tissue absorbance calculated

• Catheter geometry and optical coupling important

• Small source-detector separations: light penetrates tissue while restricting volume interrogated

~1.5 mm

Light inTo spectrometer

wavelengthAbso

rban

ce

plaqueinterfaceEstimated penetration @

760 nm ~ 0.65 millimeters

Methods• 5 human carotid endarterectomized

plaques were collected and placed immediately in a humidified, 37°C controlled temperature glove-box type incubator.

• A 3Fr fiber optic 360° side-viewing catheter prototype with a 50 micron spacing was used.

• Optical reflectance spectra (400 – 1100 nm) were collected by a spectrometer (Foss NIRSystems).

3 Fr catheter prototype

Methods• Seventeen tissue pH readings were measured using micro-

electrodes and correlated with matching optical reflectance spectra.

• Partial Least Squares multivariate calibration techniques were used to calibrate the absorbance spectra collected by optical catheter system to electrode pH

• Several wavelengths contribute to the NIR pH calibration equation using empirical algorithm and statistical analysis

Results• The range of the electrode pH was

6.83 to 7.54• The R2 of the determination of

tissue pH from the optical NIR calibration was 0.63.

• Root Mean Squared Deviation (RMSD) was 0.14 pH units.

6.60

6.80

7.00

7.20

7.40

7.60

6.60 6.80 7.00 7.20 7.40 7.60

electrode pH

NIR

pH

R2 = 0.63RMSD = 0.14 pH units

Ongoing and Future Work

• Plaque pH heterogeneity evident in physiological media• Increase study size (n100 pts) using physiological media to

mimic in-vivo conditions• Develop other NIR-based metabolic and structural correlates

to plaque vulnerability• Develop the clinically relevant coronary device• What plaque pH is considered vulnerable?

Conclusions

This study demonstrates that plaque tissue pH can be feasibly determined with NIR spectroscopy ex vivo in a localized area. It also suggests that with further improvements, a spectroscopic fiber optic catheter meet the long-term goal of detection of vulnerable plaques based on pH.

Acknowledgements

St. Luke’s Episcopal Hospital, Houston TXDepartment of Cardiology, University of Texas Houston Health Science CenterDivision of Vascular Biology, Texas Heart InstituteDepartment of Surgery, University of Massachusetts Medical School

This work was supported through the University of Texas Houston (DREAMSTM

Project) from the U.S. Army Medical Command.