From Leiden University Medical Center (T.J.R.), Leiden, The Netherlands;
Massachusetts Institute of Technology (J.F.B. III, G.D., M.S.F.), Cambridge,
Mass; Medical Device Consultants, Inc (M.L.F.), North Attleboro, Mass;
University Hospitals of Cleveland and Case Western Reserve University (M.F.),
Cleveland, Ohio; The Cleveland Clinic Foundation (J.L.M., J.R.K.), Cleveland,
Ohio; and Boston Heart Foundation & Division of Health Sciences and
Technology, Harvard University and Massachusetts Institute of Technology
(R.S.L.), Cambridge.
Correspondence to T.J. Römer, MD, Department of Cardiology, C-5P, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail romer{at}cardio.azl.nl
Background—Lesion composition,
rather than size or volume, determines whether an atherosclerotic
plaque will progress, regress, or rupture, but current techniques
cannot provide precise quantitative information about lesion
composition. We have developed a technique to assess the pathological
state of human coronary artery samples by quantifying their
chemical composition with near-infrared Raman spectroscopy.
Methods and Results—Coronary artery samples (n=165)
obtained from explanted recipient hearts were illuminated with 830-nm
infrared light. Raman spectra were collected from the tissue and
processed to quantify the relative weights of cholesterol,
cholesterol esters, triglycerides and
phospholipids, and calcium salts in the examined artery location. The
artery locations were then classified by a pathologist and grouped as
either nonatherosclerotic tissue, noncalcified plaque, or calcified
plaque. Nonatherosclerotic tissue, which included normal artery and
intimal fibroplasia, contained an average of
Conclusions—The pathological state of a given human
coronary artery may be assessed by quantifying its chemical
composition, which can be done rapidly with Raman spectroscopic
techniques. When Raman spectra are obtained clinically via optical
fibers, Raman spectroscopy may be useful in monitoring the progression
and regression of atherosclerosis, predicting plaque
rupture, and selecting proper therapeutic intervention.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Histopathology of Human Coronary Atherosclerosis by Quantifying Its Chemical Composition With Raman Spectroscopy
4±3%
cholesterol, whereas noncalcified plaques had 26±10%
and calcified plaques 19±10% cholesterol in the
noncalcified regions. The average relative weight of calcium salts was
1±2% in noncalcified plaques and 41±21% in calcified plaques.
To make this quantitative chemical information clinically useful, we
developed a diagnostic algorithm, based on a first set of
97 samples, that demonstrated a strong correlation of the relative
weights of cholesterol and calcium salts with
histological diagnoses of the same locations. This
algorithm was then prospectively tested on a second set of 68 samples.
The algorithm correctly classified 64 of these new samples, thus
demonstrating the accuracy and robustness of the method.
Key Words: spectroscopy • diagnosis • atherosclerosis
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