The goal of this project is to determine the metabolic disturbances within tissue produced by disease and therapy. High- energy phosphates, pH, lactate, and other metabolites will be measured in surface tumors, heart, and kidneys of human patients, using 31P and 1H NHR. Both Bo and B1 localization techniques will be developed, simulated, tested on phantoms, normal subjects, and patients. Cancer studies will examine the possibility that metabolic changes are a sensitive and early index of the response to therapy. These studies will begin with large superficial squamous cell carcinomas of the head and neck. After completing a survey to characterize metabolic composition, heterogeneity, and variability, pilot experiments will determine the effects and time course of chemo- and radiation therapy. A prospective trial will correlate the spectral changes with the ultimate response to therapy, determined by MRI, CT, and ultimate outcome. Heart studies are designed to test the hypothesis that disorders of cardiac energy metabolism may be responsible for functional abnormalities in cardiac disease. 31P and 1H NMR studies of coronary ischemia in the pig will be continued using surgically implanted coils. Spectral localization techniques will be developed using the pig and human subjects. The effects of exercise and pacing will be determined and the metabolic alterations produced by myocardiopathy, hypertrophy, transplant rejection, and ischemia will be examined. Human kidney studies are aimed at investigating the metabolic changes produced by acute tubular necrosis. Once localization techniques are developed, and the normal kidney is examined, the changes associated with acute tubular necrosis will be characterized. Renal function will be correlated with NMR results to determine if spectral changes predict the outcome, or the response to therapy in a series of patients with ATN.
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