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Title: Magnetic Resonance Imaging haemodynamic modelling in chronic liver disease : development, validation and translation
Author: Chouhan, M. D.
ISNI:       0000 0004 5366 2665
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2015
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Though haemodynamic changes underpin the pathophysiology of chronic liver disease, there are currently no robust non-invasive methods available for their assessment. I propose ‘caval subtraction’ phase contrast MRI (PCMRI) a novel method to measure total liver blood flow (TLBF) and hepatic arterial (HA) flow using PCMRI measurements of caval and portal venous (PV) flow. I validate this method at 9.4T and 3.0T to demonstrate: agreement between preclinical PCMRI and invasive transit-time ultrasound (TTUS) and fluorescent microsphere measurements of flow parameters; good consistency between clinical caval subtraction PCMRI and independent direct PCMRI measurements; encouraging correlations between PCMRI and invasive ICG clearance in patients; and good seven-day reproducibility of PCMRI derived haemodynamic parameters in normal volunteers. Using dynamic contrast enhanced (DCE) MRI on a 3.0T system, I demonstrate improved seven-day reproducibility using dual input single compartment pharmacokinetic modelling with a novel method for obtaining physiological vascular input function delays, correction of arterial input functions using PCMRI aortic flow and use of PCMRI estimations of TLBF to correct DCE MRI quantification. I also implement arterial spin labelling (ASL) at 9.4T and demonstrate a tendency for ASL to underestimate PCMRI hepatic parenchymal perfusion. Using bile-duct ligated (BDL) rats to study cirrhosis, I demonstrate that these have reduced TLBF and HA fraction at baseline, impaired HA regulation and buffer response, cirrhotic cardiomyopathy, and a failure to match hepatic circulatory demands with increased liver:body mass ratio. Acute-on-chronic liver failure (simulated using endotoxaemia) demonstrates reductions in TLBF, HA flow, absence of normal sepsis-induced hepatic hyperaemia and blunted cardiac systolic response. Studies in cirrhotic patients demonstrate increased TLBF and HA flow in higher risk portal hypertensive patients; that HA flow, HA fraction and cardiac output are important correlative parameters with hepatic venous pressure gradient and that caval subtraction PCMRI has potential in evaluating treatments for portal hypertension.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available