Research Project
6168470
Our work focuses on early events in the process of alcohol- induced hepatic damage. We propose to noninvasively study the dynamic response of the chronic alcohol-treated liver within the living rat to acute alcohol, hypoxic and hyperoxic challenges. Functional Magnetic Resonance Imaging (fMRI) is a new technique in which changes in the oxygenation (deoxy-/oxy-hemoglobin ratios) of a tissue within a subject or patient can be detected noninvasively. This technique has generated great excitement in the CNS community, since those regions of the brain involved in a specific task show small but detectable changes in oxygenation. Similarly, fMRI has great potential as a method for studying oxygenation in other tissues, where the oxygenation changes can be much greater. To our knowledge, we are the only research group using fMRI to study these changes in the liver. We will study oxygenation changes at the sinusoidal level using a modified T2-weighted fMRI experiment, in addition to the more conventional T2* weighted fMRI techniques. For our chronic alcohol feeding protocol, we will use the Lieber-DeCarli liquid diet, rather than more traumatic direct intragastric protocols. Our preliminary results with this animal model indicate no appreciable effects of alcohol of hepatic oxygenation levels in the animals at rest. However, we see large oxygenation changes during various challenges, and chronic alcohol treatment substantially alters these dynamic responses. We want to validate these results, and extend them to lower alcohol protocols that are better models for moderate human alcohol consumption. This study also lays the groundwork for simple noninvasive clinical diagnostic tests to evaluate liver oxygenation status in human patients, as a possible early predictor of subsequent alcoholic liver disease.
