High-resolution 1H NMR spectral signature from human atheroma

Coronary artery disease due to atherosclerosis takes the lives of approximately 550,000 Americans each year--an enormous toll. Put in economic terms, the cost to the United States alone has been estimated to exceed 60 billion dollars annually. We have found that well-resolved proton (1H) NMR spectra can be obtained from human atheroma (fatty plaque), despite its macroscopic solid appearance. The fraction of the total spectral intensity corresponding to the sharp 1H NMR signals is temperature dependent and approaches unity at body temperature (37 degrees C). Studies of the total lipids extracted from atheroma and cholesteryl esters were conducted to identify the chemical and physical origin of the spectral signature. The samples were characterized through assignment of their chemical shifts and by measurement of their T1 and T2 relaxation times as a function of magnetic field strength. The results suggest that the relatively sharp 1H NMR signals from human atheroma (excluding water) are due to a mixture of cholesteryl esters, whose liquid-crystalline to isotropic fluid phase transition is near body temperature. Preliminary applications to NMR imaging of human atheroma are reported, which demonstrate early fatty plaque formation within the wall of the aorta. These findings offer a basis for noninvasive imaging by NMR to monitor early and potentially reversible stages of human atherogenesis.