The goal of this proposal is to develop a methodology, using near infrared (NIR) Raman spectroscopy, as a quantitative method, for in situ spectral analysis of atherosclerosis and its progression in human peripheral arteries. With this technique, information on the arterial morphology and chemical composition can be obtained rapidly, accurately and remotely. Therefore, it has the potential to provide quantitative measurement of histomorphological and histopathological markers for both the presence and extent of atherosclerotic alterations. The specific goals of the proposal are to: 1) perform basic, quantitative studies of the relationship between the Raman spectrum and the artery histochemistry and morphology. We propose several approaches for characterizing fully the spectroscopic variability of the NIR Raman signals with disease-associated alterations of artery. We have planned specific experiments to compare Raman spectra with artery morphology, and use this information to establish diagnostic decision schemes. 2) Develop a new class of highly sensitive NIR optical fiber spectral microprobes for use in operating room and clinical settings. 3) Perform clinical studies to evaluate new probe designs in vivo during peripheral vascular surgery and in the presence of interferences such as blood.