The effect of chronic hepatic diseases on hepatobiliary metabolism via multiphoton fluorescence imaging in vivo

Chih-Ju Lin^1*, Sheng-Lin Lee¹, Wei-Hsiang Wang¹, Hsuan‐Shu Lee², Chen‐Yuan Dong^1,3

¹Department of Physics, National Taiwan University, Taipei, Taiwan
²Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
³Molecular Imaging Center, National Taiwan University, Taipei, Taiwan

* Presenter:Chih-Ju Lin, email:d97222010@ntu.edu.tw

In this study, intravital multiphoton microscopy was used to quantitatively investigate hepatobiliary metabolism in chronic hepatic pathologies. Specifically, through the use of the probe molecule 6‐carboxyfluorescein diacetate(6-CFDA) as the metabolite, the effects of liver fibrosis, fatty liver, and hepatocellular carcinoma on the metabolic capabilities of mouse liver were investigated. After the acquisition of time‐lapse images, a first-order kinetic model was used to calculate rate constant resolved images of various pathologies. It was found that the ability of the liver to metabolically process the probe molecules varies among different pathologies, with liver fibrosis and fatty liver disease negatively impacted the uptake, processing, and excretion of molecules. The approach demonstrated in this work allows the study of the response of hepatic functions to different pathologies in real time and is useful for studying processes such as pharmacokinetics through direct optical imaging.

Keywords: Intravital multiphoton microscopy, hepatobiliary metabolism, first-order kinetic model