The long term goal of this research is to develop noninvasive optical instruments and methods for assessing the functional integrity of cold- stored livers prior to transplant. This research is based on the working hypothesis that in hypothermically-stored livers, areas of dysfunctional oxidative metabolism can be detected noninvasively using spectrophotometric methods. fluorescence detection of NADH and visible light reflectance detection of cytochrome redox changes will be used to examine hypothermic perfused and cold-stored rat livers under normoxic, ischemic and uncoupled conditions. The Phase l studies will demonstrate the feasibility of the working hypothesis. Equipment will be assembled to image hepatic NADH fluorescence and measure cytochrome reflectance spectra from both hypothermic perfused and cold-stored rat livers. Correlation of optical changes with hepatic function and dysfunction will be made. The methods developed will be evaluated for their sensitivity for distinguishing areas of impaired mitochondrial metabolism on a background of normal tissue. Upon successful demonstration of the working hypothesis, Phase II will adapt these concepts to development of imaging methods and to testing in a clinical environment at the liver transplant center at Harborview Medical Center, Seattle, Washington.
