ABSTRACT
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.
Footnotes
Competing interests
A.H.H., M.G., M.M. and R.B. are employees of Perspectum Diagnostics Ltd, the developer of LiverMultiScan™. A.H.H., M.G. and R.B. hold stock in the company. R.L.J. and P.S.M. are employees of GlaxoSmithKline and hold stock in the company. The remaining authors have no relevant conflicts of interest to declare. This is an academic led and reported study, with industry engagement. The role of Perspectum Diagnostics Ltd was the provision of access to multiparametric MRI methodology and blinded analysis of raw MRI data. Study design and potential conflicts do not affect adherence to policies on sharing data and materials. All study investigations, data analysis, manuscript preparation and decision to submit was undertaken by the academic center.
Author contributions
Conceptualization: R.L.J., P.S.M., J.A.F.; Methodology: R.J.L., M.M., A.H.H., T.J.K., M.G., R.B., R.L.J., P.S.M., M.A.J., J.A.F.; Software: R.J.L., M.M., A.H.H., M.G., R.B., M.A.J.; Validation: R.J.L., M.M., A.H.H., M.G., M.A.J.; Formal analysis: A.M.H., N.M., R.J.L., A.H.H., T.J.K., M.G., R.L.J., M.A.J.; Investigation: A.M.H., N.M., R.J.L., T.J.K., W.M., M.A.J., J.A.F.; Resources: R.B., P.S.M., M.A.J.; Data curation: A.M.H., T.J.K., M.A.J.; Writing - original draft: A.M.H., J.A.F.; Writing - review & editing: N.M., A.H.H., T.J.K., M.G., R.L.J., M.A.J., J.A.F.; Visualization: J.A.F.; Supervision: W.M., R.B., P.S.M., M.A.J., J.A.F.; Project administration: R.B., J.A.F.; Funding acquisition: P.S.M.
Funding
This study was funded by an unrestricted research grant from GlaxoSmithKline. J.A.F. was supported by an NHS Research Scotland/Universities Scottish Senior Clinical Fellowship. T.J.K. was supported by a Wellcome Trust Intermediate Clinical Fellowship (095898/Z/11/Z).
Supplementary information
Supplementary information available online at http://bio.biologists.org/lookup/doi/10.1242/bio.033910.supplemental
- Received February 28, 2018.
- Accepted June 8, 2018.
- © 2018. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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