Date of Award

8-11-2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Mathematics and Statistics

First Advisor

Yi Jiang

Abstract

The liver is a vital organ that carries out over 500 essential tasks, including fat metabolism, blood filtering, bile production, and some protein production. Although the structure of the liver and the role of each type of cells in the liver are well known, the biomedical and mechanical interplays within liver tissues remain unclear. Chronic liver diseases are a significant public health challenge. All chronic liver diseases lead to liver fibrosis due to excessive fiber accumulation, resulting in cirrhosis and loss of liver function. Only early stage liver fibrosis is reversible. However, early-stage liver fibrosis is difficult to diagnose. How the progression of fibrosis changes the mechanical properties of the liver tissue and altering the dynamics of blood flow is still not well understood. The objective of this dissertation is to integrate the understanding of liver diseases and mechanical modeling to develop several models relating liver fibrosis to blood flow. In collaboration with clinicians specialized in hepatic fibrosis, we integrated computational modeling and clinicopathologic image analysis and proposed a new technology for early stage fibrosis detection. The key results of this research include: (1) A mathematical model of liver fibrosis progression connecting the cellular and molecular mechanisms of fibrosis to tissue rigidity; (2) A novel machine learning-based algorithm to automatically stage liver fibrosis based on pathology images; (3) A physics model to illustrate how the liver stiffness affects the blood flow pattern, predicting a direct relationship between fibrosis stage and ultrasound Doppler measurement of liver blood flow; (4) Statistical analysis of clinical ultrasound Doppler data from fibrosis patients confirming our model prediction. These results lead to a novel noninvasive technology for detecting early stages of liver fibrosis with high accuracy.

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