The overall aim of this proposal is to develop magnetic resonance imaging (MRI) as a tool to characterize organ-selective effects of alcohol during the development of alcohol dependence and during recovery, and to assess whether certain paramagnetic MRI contrast agents enhance delineation of ethanol-induced tissue changes. A dietary procedure for the development of alcohol dependence will be employed and at 3,6,9 and 12 months of treatment and following one and two months of abstinence, rats will be examined for alcohol effects. Each group will have appropriate pair-fed and age-matched controls. Alcohol effects will be evaluated in brain and kidney. Established neurohistologic, pathologic and renal function analyses will describe the developing organ dysfunctions and, at the noted time points, magnetic resonance measurements will be obtained for identically treated animals; In vitro measurement of T1 and T2 in dissected brain and kidney, under controlled and standardized conditions, will provide a meaningful correlation of the variations of tissue water with specific pathological conditions. These measurements will contribute to the understanding of the basic processes underlying the changes observed in in vivo magnetic resonance images obtained immediately prior to the in vitro data. In addition, paramagnetic contrast agents (manganese (III) mesotetraphenylporphine sulfonate and its derivatives) will be evaluated for their ability to more sharply delineate and characterize the alcohol effects. It is expected that these experiments, in a well controlled animal model, will provide solid data toward the development of the potential of magnetic resonance imaging as a useful technique to assess organ changes in the development of chronic alcoholism in man.
