Chouhan, MD; (2015) Magnetic Resonance Imaging haemodynamic modelling in chronic liver disease: development, validation and translation. Doctoral thesis , UCL (University College London).

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Abstract

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.

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