SHAPE Society

1. 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

2. Everybody has atherosclerosis, the question is who has
vulnerable plaque
Sudden Cardiac Death
Acute MI
Vulnerable
Plaque(s)

3. 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…

4. - 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

5. 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

6. 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)

7. 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 1100
wavelength
absorbance(a.u.)
Calcified
Thrombus
Fibrous

8. 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.

9. 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 in
To spectrometer
wavelength
Absorbance
plaque
interfaceEstimated penetration @
760 nm ~ 0.65 millimeters

10. 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

11. 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

12. 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
NIRpH
R2
= 0.63
RMSD = 0.14 pH units

13. Ongoing and Future Work
• Plaque pH heterogeneity evident in physiological media
• Increase study size (n≈100 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?

14. 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.

15. Acknowledgements
St. Luke’s Episcopal Hospital, Houston TX
Department of Cardiology, University of Texas Houston Health Science Center
Division of Vascular Biology, Texas Heart Institute
Department 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.