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Scott, Robert A.D. (2020) Quantitative magnetic resonance imaging to evaluate patients with liver cirrhosis. PhD thesis, University of Nottingham.

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Abstract

Introduction:

The incidence and mortality of liver disease is increasing. Most morbidity and mortality in patients with liver cirrhosis results from the development and progression of portal hypertension, characterised by increased intrahepatic resistance and splanchnic vasodilatation. Transjugular hepatic venous pressure gradient (HVPG) is the only validated technique for the assessment of portal pressure to stratify an individual’s risk and changes following therapeutic interventions. However, HVPG measurements are expensive, invasive and only available in specialist centres which precludes the use of HVPG in routine clinical practice.

Magnetic Resonance Imaging (MRI) technologies provide unique methods for imaging the whole liver and abdomen. As a result, several favourable characteristics required to stratify chronic liver diseases are obtained. These methodologies are non-invasive, provide objective measurements, are organ-specific and do not use ionising radiation. They measure multiple parameters in a single scan session. Uniquely amongst imaging modalities, it is possible to concordantly assess several different measures in the same scan session.

Methodology:

All three prospective studies compared non-invasive quantitative MRI measures to current gold-standard measures.

In the first part of the thesis, I investigated the effect of field strength on surrogate MR measures of portal pressure. A prospective cross-sectional study of patients undergoing transjugular liver biopsies across two sites recruited participants to attend for a single study visit within 12 weeks. Patients underwent transient elastography, blood tests and a single non-invasive MRI scan at a field strength of 3 Tesla. All measures were compared to HVPG.

In the second part of the thesis, I investigated the effects of Direct Acting Antiviral therapy given to patients with advanced liver disease caused by Hepatitis C virus. Patients eligible for treatment were invited to take part in a prospective observational study. Participants underwent an MRI scan before and after treatment completion (within 12 weeks of last tablet swallowed). Patients followed standard management protocols for therapy and monitoring. Routine clinical information including medical history, clinical examination and laboratory values were recorded for each participant and compared to the MRI measures.

In the third part of the thesis, I aimed to develop a novel quantitative MRI tool to evaluate increased small bowel permeability in a double-blind, placebo-controlled, healthy volunteer study. Development of bacterial translocation is believed to be a key prognostic event precipitating decompensation and life-threatening complications in patients with advanced chronic liver disease. The best available tools to evaluate gut permeability were compared with a newly developed MRI assessment of the small bowel. Provocation with enteral Indomethacin administration, an accepted positive control for experimental medicine studies, was used to compare the MRI measures to bowel permeability assessed by the Lactulose/Mannitol urinary excretion ratio (LMR).

Results:

In the first prospective cross-sectional study, 39 patients were recruited who had MRI data for comparison to HVPG. At 3 Tesla, HVPG significantly correlated with: iron corrected liver longitudinal relaxation time (T1: R=0.60, p<0.001), Spleen T1 (R=0.599, p<0.001), SMA velocity (R=0.45, p=0.008) and Splenic artery flow (R=0.456, p=0.017). There was a significant correlation of cardiac index and Splenic artery flow as well as a clear correlation of differing azygous vein flow in the presence or absence of varices. Combining this data with the original derivation data at 1.5 Tesla (n=40) showed a field strength dependent ceiling effect of structural measures and a reduction in SMA and splenic artery velocity >15 mmHg.

In the second prospective observational study of patients undergoing new treatments for chronic Hepatitis C infection, multiparametric MRI, in a time window of 3-6 months between pre- and post-treatment scans, demonstrated changes in hepatic composition in 17 patients. Liver longitudinal relaxation time (T1, 35±4 ms), transverse relaxation time (T2, 2.5±0.8 ms; T2*, 3.0±0.7 ms) and liver perfusion (28.1±19.7ml/100g/min) all significantly reduced. These measures are likely linked to reduced pro-inflammatory milieu, including interstitial oedema, within the liver. By chance, seven patients were diagnosed with hepatocellular carcinoma after starting treatment in whom pre-treatment MRI lesions could be identified on the research scans.

In the double-blind placebo-controlled study of 22 healthy volunteers, only a newly developed measure of small bowel T2 significantly increased (70 ± 36 ms vs 115 ± 63ms, p=0.017) and correlated (R=0.68, p<0.01) with increased LMR following indomethacin administration (0.019 (IQR 0.016-0.026) to 0.025 (IQR 0.021-0.039), p=0.002).

Conclusions:

This thesis provides data that suggests a non-contrast MRI scan may uniquely be able to simultaneously evaluate multiple measures of prognostic importance in patients with chronic liver disease including liver fibrosis, portal pressure, the development of a hyperdynamic circulation, small bowel permeability and hepatocellular carcinoma surveillance. These findings need to be validated, optimised and shown to evaluate efficacy of interventions in order to lead to clinical adoption. MRI has the potential to be a key non-invasive tool to evaluate the efficacy of interventions in chronic liver disease and stratify patients according to the potential clinical outcomes.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Aithal, Guruprasad A. Guha, Indra Neil Gowland, Penny Francis, Susan
Keywords:	MRI, Magnetic resonance imaging, Liver disease, Prognostic measures, Portal pressure, Hyperdynamic circulation, Small bowel permeability, Hepatocellular carcinoma surveillance
Subjects:	W Medicine and related subjects (NLM Classification) > WN Radiology. Diagnostic imaging
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	60130
Depositing User:	Scott, Robert
Date Deposited:	09 Dec 2020 08:44
Last Modified:	21 Jan 2021 04:30
URI:	https://eprints.nottingham.ac.uk/id/eprint/60130

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