Image-based tissue informatics - TAA induced hepatotoxicity model

Abstract

Hepatic toxicity appears to be the major problem causing market withdrawal of numerous drugs in the pharmaceutical industry. In this project, we aimed to establish an in vivo model of hepatotoxicity using medaka fish, and to extract quantitative information from tissue images taken by nonlinear optical microscopy. Thioacetamide was used for the production of hepatic lesion in medaka fish. The most effective thioacetamide concentrations for chronic and acute liver damage were determined. RT-PCR and Hematoxylin & Eosin staining were used to examine the mRNA expression level of several genes and the architecture of tissue in damaged liver. We have also developed and applied Two-Photon Excitation Fluorescence/ Second Harmonic Generation Microscopy for imaging of unstained liver tissue. Comprehensive imaging processing algorithms were developed for quantification of collagen content and cell necrosis. The whole liver of liver-RFP transgenic fish was imaged in three-dimensional manner. The imaging depth of nonlinear microscopy was investigated.