HISTOPATHOLOGY OF HUMAN CORONARY ATHEROSCLEROSIS BY QUANTIFYING ITS CHEMICAL-COMPOSITION WITH RAMAN-SPECTROSCOPY

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 th eir chemical composition with near-infrared Raman spectroscopy. Method s and Results-Coronary artery samples (n=165) obtained from explanted recipient hearts were illuminated with 830-nm infrared light. Raman sp ectra were collected from the tissue and processed to quantify the rel ative weights of cholesterol, cholesterol esters, triglycerides and ph ospholipids, and calcium salts in the examined artery location. The ar tery locations were then classified by a pathologist and grouped as ei ther nonatherosclerotic tissue, noncalcified plaque, or calcified plaq ue. Nonatherosclerotic tissue, which included normal artery and intima l fibroplasia, contained an average of approximate to 4+/-3% cholester ol, whereas noncalcified plaques had approximate to 26+/-10% and calci fied plaques approximate to 19+/-10% cholesterol in the noncalcified r egions. The average relative weight of calcium salts was 1+/-2% in non calcified plaques and 41+/-21% in calcified plaques. To make this quan titative chemical information clinically useful, we developed a diagno stic algorithm, based on a first set of 97 samples, that demonstrated a strong correlation of the relative weights of cholesterol and calciu m salts with histological diagnoses of the same locations. This algori thm was then prospectively tested on a second set of 68 samples, The a lgorithm correctly classified 64 of these new samples, thus demonstrat ing the accuracy and robustness of the method. Conclusions-The patholo gical state of a given human coronary artery may be assessed by quanti fying its chemical composition, which can be done rapidly with Raman s pectroscopic techniques. When Raman spectra are obtained clinically vi a optical fibers, Raman spectroscopy may be useful in monitoring the p rogression and regression of atherosclerosis, predicting plaque ruptur e, and selecting proper therapeutic intervention.