title: Development of quantitative imaging biomarkers for assessing hepatic function and metabolism
Creators: name: Ball, Christopher
Publisher: name: University of Liverpool Repository
Year: 2026

description: Liver diseases represent one of the fastest growing causes of mortality in the United Kingdom and around the world. The prevalence of metabolic associated fatty liver disease is estimated to already equal thirty percent of the global population, with the number of individuals affected rising yearly. Liver pathologies therefore represent an enormous challenge – to both individuals, and health services. Assessment of liver disease accurately using non-invasive imaging methods, is consequently of high importance, both in terms of replicating pathological processes in preclinical animal models, as well as the tools used for assessment. 
This thesis aims to apply non-invasive in-vivo imaging methods to emerging and established rodent models of liver disease. Understanding disease progression, from cause to death, is essential in realising novel treatment pathways. Animal models provide a platform for the study of full disease progression, and through the use of in-vivo imaging, this can be done in the least destructive manner possible. 
The first study in this thesis evaluates and characterises a newly developed model of diet induced metabolic associated fatty liver disease through magnetic resonance. Dixon imaging and spectroscopy are applied to quantify hepatic and abdominal fat alterations in the early stages of disease progression. Significant hepatic lipid accumulation is observed as well as increasing fat storage in the abdominal region. Metabolic and transcriptomic assessment is also performed, to evaluate whether similar changes occur in mice as they do in humans. Insulin signalling is found to be disrupted, alongside pathological gene expression changes. 
The second study employs a widely used model of steatohepatitis, with this disease being a severe form of metabolic associated fatty liver disease. Magnetic resonance techniques demonstrated hepatic volume expansion, lipid accumulation and the development of nodular lesions in the organ. Ultrasound, however, was unable to detect liver fibrosis. This study was performed to gain a deeper understanding of disease progression in this model than what is currently known. 
The final project of this thesis uses magnetic resonance and computed tomography techniques to ascertain the pathway of methotrexate hepatotoxicity. Methotrexate is a widely used chemotherapeutic and immunosuppressant agent, but the causes of its liver-damaging effects are unknown. Angiography was performed in-vivo through magnetic resonance and ex-vivo through CT to assess blood vessel involvement in this disease course. Significant enlargement in vessel radii and volume were observed through in-vivo methods, as well as a pathologically altered T1 relaxation. 
The work successfully demonstrates its application of in-vivo imaging techniques for liver disease assessment. Data in this thesis provides a greater understanding of disease progression in three preclinical animal models, with the aim of enabling future research into therapeutic strategies.