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 PhD, S. Ward Casscells MD, Morteza Naghavi MD
Texas Heart Institute
Product Line Review/TATRC/DREAMS
Tuesday Jan 7th
, 2003

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.