The long term objective of this study is to develop new in vivo, noninvasive methods of detecting ethanol induced hepatocyte abnormalities using proton MRI and a new manganese/pyridoxal-5-phosphate paramagnetic contrast agent (S-095). S-095 is a unique paramagnetic MRI contrast agent capable of estimating hepatocyte damage and simultaneously serving as an intrahepatocyte MRI contrast agent.
The specific aims are to: l.Utilize MRI contrast enhancement studies to detect hepatocyte damage. 2. Determine if these methods can be used to measure metabolic toxicity arising from ethanol ingestion, and correlate these changes with biochemical and histological properties of the tissue. 3.Evaluate the induction, progression, and potential reversibility of alcohol induced hepatic abnormalities using MRI. MRI data (ROI [Intensity], T1, T2, and Liver size) are to be obtained in rats given graded amounts of ethanol (Lieber-DeCarli diet) for variable periods of time. Histology, plasma and tissue enzymes, and quantitative electron microscopic studies of vesicular transport mechanisms (using electron dense tracers) are to be obtained at appropriate intervals for comparison with the MRI/S095 studies.
|Sidhu, M K; Muller, H H; Aggeler, J et al. (1993) Manganese dipyridoxal diphosphate-enhanced magnetic resonance imaging in the evaluation of hepatocyte function. Invest Radiol 28:903-10|