Non-invasive assessment of liver disease in rats using multiparametric magnetic resonance imaging: a feasibility study.

Non-invasive quantitation of liver disease using multiparametric magnetic resonance imaging (MRI) could refine clinical care pathways, trial design and preclinical drug development. The aim of this study was to evaluate the use of multiparametric MRI in experimental models of liver disease. Liver injury was induced in rats using 4 or 12 weeks of carbon tetrachloride (CCl4) intoxication and 4 or 8 weeks on a methionine and choline deficient (MCD) diet. Liver MRI was performed using a 7.0 Tesla small animal scanner at baseline and specified timepoints after liver injury. Multiparametric liver MRI parameters [T1 mapping, T2* mapping and proton density fat fraction (PDFF)] were correlated with gold standard histopathological measures. Mean hepatic T1 increased significantly in rats treated with CCl4 for 12 weeks compared to controls [1122±78 ms versus 959±114 ms; d=162.7, 95% CI (11.92, 313.4), P=0.038] and correlated strongly with histological collagen content (rs=0.717, P=0.037). In MCD diet-treated rats, hepatic PDFF correlated strongly with histological fat content (rs=0.819, P<0.0001), steatosis grade (rs=0.850, P<0.0001) and steatohepatitis score (rs=0.818, P<0.0001). Although there was minimal histological iron, progressive fat accumulation in MCD diet-treated livers significantly shortened T2*. In preclinical models, quantitative MRI markers correlated with histopathological assessments, especially for fatty liver disease. Validation in longitudinal studies is required.This article has an associated First Person interview with the first author of the paper.

Multiparametric magnetic resonance imaging for quantitation of liver disease: a two-centre cross-sectional observational study.

LiverMultiScan is an emerging diagnostic tool using multiparametric MRI to quantify liver disease. In a two-centre prospective validation study, 161 consecutive adult patients who had clinically-indicated liver biopsies underwent contemporaneous non-contrast multiparametric MRI at 3.0 tesla (proton density fat fraction (PDFF), T1 and T2* mapping), transient elastography (TE) and Enhanced Liver Fibrosis (ELF) test. Non-invasive liver tests were correlated with gold standard histothological measures. Reproducibility of LiverMultiScan was investigated in 22 healthy volunteers. Iron-corrected T1 (cT1), TE, and ELF demonstrated a positive correlation with hepatic collagen proportionate area (all p < 0·001). TE was superior to ELF and cT1 for predicting fibrosis stage. cT1 maintained good predictive accuracy for diagnosing significant fibrosis in cases with indeterminate ELF, but not for cases with indeterminate TE values. PDFF had high predictive accuracy for individual steatosis grades, with AUROCs ranging from 0.90-0.94. T2* mapping diagnosed iron accumulation with AUROC of 0.79 (95% CI: 0.67-0.92) and negative predictive value of 96%. LiverMultiScan showed excellent test/re-test reliability (coefficients of variation ranging from 1.4% to 2.8% for cT1). Overall failure rates for LiverMultiScan, ELF and TE were 4.3%, 1.9% and 15%, respectively. LiverMultiScan is an emerging point-of-care diagnostic tool that is comparable with the established non-invasive tests for assessment of liver fibrosis, whilst at the same time offering a superior technical success rate and contemporaneous measurement of liver steatosis and iron accumulation.

Assessment of Haemodynamic Response to Nonselective Beta-Blockers in Portal Hypertension by Phase-Contrast Magnetic Resonance Angiography.

A significant unmet need exists for accurate, reproducible, noninvasive diagnostic tools to assess and monitor portal hypertension (PHT). We report the first use of quantitative MRI markers for the haemodynamic assessment of nonselective beta-blockers (NSBB) in PHT. In a randomized parallel feasibility study in 22 adult patients with PHT and a clinical indication for NSBB, we acquired haemodynamic data at baseline and after 4 weeks of NSBB (propranolol or carvedilol) using phase-contrast MR angiography (PC-MRA) in selected intra-abdominal vessels. T1 mapping of liver and spleen was undertaken to assess changes in tissue composition. Target NSBB dose was achieved in 82%. There was a substantial reduction from baseline in mean average flow in the superior abdominal aorta after 4 weeks of NSBB therapy (4.49 ± 0.98 versus 3.82 ± 0.86 L/min, P = 0.03) but there were no statistically significant differences in flow in any other vessels, even in patients with >25% decrease in heart rate (47% of patients). Mean percentage change in liver and spleen T1 following NSBB was small and highly variable. In conclusion, PC-MRA was able to detect reduction in cardiac output by NSBB but did not detect significant changes in visceral blood flow or T1. This trial was registered with the ISRCTN registry (ISRCTN98001632).