| Summary: | 博士 === 臺灣大學 === 物理研究所 === 98 === Liver, the largest internal organ, is a major chemical factory in the body responsible for important functions such as metabolism, detoxification, nutrient storage, and serum protein production. Traditionally, the study of the liver depended heavily on histological techniques, which are limited to ex-vivo observations and lack dynamic information of the hepatobiliary system. In order to study hepatic metabolism in vivo, we have designed a hepatic imaging chamber made of biocompatible titanium alloy (6V4Al-Ti). Combining the chamber with multiphoton microscopy, we were able to monitor and quantitatively analyze the hepatobiliary metabolism to single cell resolution in vivo. In addition to studying metabolic dynamics, we applied our methodology to investigate mechanism of cell-death. We found that and determined a critical limit for hepatocyte death. We further developed a model based on first order rate equation to model the observed variation of 6-CFDA fluorescence intensity with time and estimate the metabolic capability of hepatocytes. Specifically, we found that zonal difference in the metabolic activity can be revealed by the distribution of the model parameters. Our approach allows the intravital observation of hepatic activities such as acetaminophen (APAP), common bile duct ligation (CBDL), Lipopolysaccharides (LPS), and CCl4. This thesis demonstrated that intravital multiphoton imaging could be used to reveal and quantify metabolic changes in the mouse liver and its potential application in studying many liver disorders.
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