Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy

Background: Recent studies have shown that chemical composition and morphol ogy, rather than anatomy (degree of stenosis), determine atherosclerotic pl aque instability and predict disease progression. Current clinical diagnost ic techniques provide accurate assessment of plaque anatomy, but have limit ed capability to assess plaque morphology in vivo. Here we describe a techn ique for a morphology-based diagnosis of atherosclerosis in the coronary ar teries using Raman spectroscopy that can potentially be performed in vivo u sing optical fiber technology. Methods: Raman tissue spectra were collected from normal and atherosclerotic coronary artery samples in different stage s of disease progression (n = 165) from explanted transplant recipient hear ts (n = 16). Raman spectra from the elastic laminae (EL), collagen fibers ( CF), smooth muscle cells (SMC), adventitial adipocytes (AA) or fat cells. f oam cells (FC), necrotic core (NC). cholesterol crystals (CC), iii-carotene containing crystals (beta -C), and calcium mineralizations (CM) were used as basis spectra in a linear least squares-minimization (LSM) model to calc ulate the contribution of these morphologic structures to the coronary arte ry tissue spectra. Results: We developed a diagnostic algorithm that used t he fit-contributions of the various morphologic structures to classify 97 c oronary artery samples in an initial calibration data set as either nonathe rosclerotic, calcified plaque. or noncalcified atheromatous plaque. The alg orithm was subsequently tested prospectively in a second validation data se t, and correctly classified 64 (94%) of 68 coronary artery samples. Conclus ions: Raman spectroscopy provides information about the morphologic composi tion of intact human coronary artery without the need for excision and micr oscopic examination. In the future, it may be possible to use this techniqu e to analyze the morphologic composition of atherosclerotic coronary artery lesions and assess plaque instability and disease progression in vivo. (C) 2001 Elsevier Science Inc. All rights reserved.