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Title: Quantitative magnetic resonance imaging in evaluating haemodynamic changes in portal hypertension
Author: Palaniyappan, Naaventhan
ISNI:       0000 0004 7228 0435
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2017
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The majority of complications in patients with cirrhosis result from the development and progression of portal hypertension characterised by increased intrahepatic resistance and progressive splanchnic vasodilation. Hepatic venous pressure gradient (HVPG) measurement is the only validated technique to accurately evaluate changes in portal pressure. However, HVPG measurements are invasive and available only in specialised hepatology units, precluding its use in routine clinical practice. In the first study, we evaluated the use of non-contrast quantitative magnetic resonance imaging (MRI) as a surrogate measure of portal pressure. 30 patients undergoing HVPG measurement were prospectively recruited. MR parameters of longitudinal relaxation time (T1), perfusion of the liver and spleen (by arterial spin labelling), and blood flow in the portal, splanchnic and collateral circulation (by phase-contrast MRI) were assessed. We estimated the liver stiffness measurement (LSM) and Enhanced Liver Fibrosis (ELF) score. The correlation of all non-invasive parameters with HVPG was evaluated. The mean (range) HVPG of the patients was 9.8 (1-22) mmHg, and 14 patients (48%) had clinically significant portal hypertension (CSPH, HVPG ≥10 mmHg). Liver T1 relaxation time, splenic artery and superior mesenteric artery velocity correlated significantly with HVPG. Using multiple linear regression, liver T1 and splenic artery velocity remained as the two parameters in the multivariate model significantly associated with HVPG (R=0.90, p < 0.001). This correlation was maintained in patients with CSPH (R=0.85, p < 0.001). A validation cohort (n=10) showed this linear model provided a good prediction of HVPG. LSM and ELF score correlated significantly with HVPG in the whole population but the correlation was absent in CSPH. In conclusion, MR parameters related to both hepatic architecture and splanchnic haemodynamics correlate significantly with HVPG. This proposed model, confirmed in a validation cohort, could replace the invasive HVPG measurement. In the second part, we studied the use non-invasive MRI to dynamically assess changes in hepatic and collateral blood flow, liver perfusion and oxygenation in response to ingestion of a test meal (meal challenge), and hyperoxia and hypercapnia (gas challenge). These changes were compared between healthy subjects and patients with compensated cirrhosis (CC). In the meal challenge study, we evaluated the blood flow in the portal vein, hepatic artery and azygos vein, liver perfusion and blood oxygenation (using transverse relaxation time (T2*) mapping). Measures were collected at baseline and at 6-7 minute intervals from 20 to 65 minutes following a test meal (440 ml; 660 kcal) in 10 healthy participants and 10 CC patients. In healthy participants, we observed a postprandial increase in portal vein flow from baseline coupled with a reduction in hepatic artery flow from baseline, reflecting the hepatic artery buffer response (HABR). In CC patients, changes in portal vein and hepatic artery flow were smaller, with no clear HABR. In healthy participants, postprandial liver perfusion increased, but not in CC patients. There was no change in liver T2* for either group. In the gas challenge study, we evaluated the blood flow in portal vein and hepatic artery, liver perfusion and liver T2* during hyperoxia and hypercapnia in 10 healthy subjects and 4 patients with compensated cirrhosis. A sequential gas delivery breathing circuit and a prospective, feed-forward gas delivery system (RespiractTM, Thornhill Research Inc., Toronto, Canada) was used to control and monitor end-tidal O2 (PETO2) and CO2 (PETCO2) partial pressures. Hyperoxia was targeted at PETO2 ~500mmHg and hypercapnia was aimed at PETCO2 ~6mmHg above resting value. The study design consisted of 5 blocks. Blocks 1, 3 and 5 were 5 min periods at resting PETCO2 and PETO2. Blocks 2 and 4 were, in a random order, 5 mins of hyperoxia (with a 2 min transition up and down) or 5 mins of hypercapnia. We observed an increase in portal vein velocity during hypercapnia among the healthy subjects and patients with cirrhosis. There was no significant changes in liver T2* but the full-width-half-maximum (FWHM) of the distribution of the liver T2* increased in response to hyperoxia and hypercapnia in both groups. Subjects with low T2* at baseline exhibited a smaller change in FWHM following the gas challenge. The within session and inter-session coefficient of variation (CoV) the blood flow measurement using phase-contrast MRI in healthy subjects was less than 15%. If our findings are confirmed in external validation studies, non-invasive MRI can be used as a surrogate measure of HVPG. Assessment of postprandial dynamic changes in hepatic, splanchnic and collateral circulation using MRI could potentially be used to stratify patients with portal hypertension and study the effects of potential novel treatments for portal hypertension.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: WI Digestive system