Assessment of hepatic transporter function in rats using dynamic gadoxetate-enhanced MRI: a reproducibility study
Journal article, 2024

Objective: Previous studies have revealed a substantial between-centre variability in DCE-MRI biomarkers of hepatocellular function in rats. This study aims to identify the main sources of variability by comparing data measured at different centres and field strengths, at different days in the same subjects, and over the course of several months in the same centre. Materials and methods: 13 substudies were conducted across three facilities on two 4.7 T and two 7 T scanners using a 3D spoiled gradient echo acquisition. All substudies included 3–6 male Wistar-Han rats each, either scanned once with vehicle (n = 76) or twice with either vehicle (n = 19) or 10 mg/kg of rifampicin (n = 13) at follow-up. Absolute values, between-centre reproducibility, within-subject repeatability, detection limits, and effect sizes were derived for hepatocellular uptake rate (Ktrans) and biliary excretion rate (kbh). Sources of variability were identified using analysis of variance and stratification by centre, field strength, and time period. Results: Data showed significant differences between substudies of 31% for Ktrans (p = 0.013) and 43% for kbh (p < 0.001). Within-subject differences were substantially smaller for kbh (8%) but less so for Ktrans (25%). Rifampicin-induced inhibition was safely above the detection limits, with an effect size of 75 ± 3% in Ktrans and 67 ± 8% in kbh. Most of the variability in individual data was accounted for by between-subject (Ktrans = 23.5%; kbh = 42.5%) and between-centre (Ktrans = 44.9%; kbh = 50.9%) variability, substantially more than the between-day variation (Ktrans = 0.1%; kbh = 5.6%). Significant differences in kbh were found between field strengths at the same centre, between centres at the same field strength, and between repeat experiments over 2 months apart in the same centre. Discussion: Between-centre bias caused by factors such as hardware differences, subject preparations, and operator dependence is the main source of variability in DCE-MRI of liver function in rats, closely followed by biological between-subject differences. Future method development should focus on reducing these sources of error to minimise the sample sizes needed to detect more subtle levels of inhibition.

Magnetic resonance imaging

Gadolinium ethoxybenzyl DTPA

Chemical and drug induced liver injury

Reproducibility of results

Rats

Author

Ebony R. Gunwhy

University of Sheffield

Catherine D.G. Hines

GlaxoSmithKline, USA

Claudia Green

Bayer AG

Iina Laitinen

Antaros Medical AB

Sanofi-Aventis Deutschland GmbH

Sirisha Tadimalla

The University of Sydney

Paul Hockings

Antaros Medical AB

Chalmers, Electrical Engineering, Signal Processing and Biomedical Engineering

Gunnar Schütz

Bayer AG

J. Gerry Kenna

Bioxydyn Limited

Steven Sourbron

University of Sheffield

John C Waterton

Faculty of Biology, Medicine and Health

Bioxydyn Limited

Magnetic Resonance Materials in Physics, Biology, and Medicine

0968-5243 (ISSN) 1352-8661 (eISSN)

Vol. 37 4 697-708

Subject Categories

Radiology, Nuclear Medicine and Medical Imaging

DOI

10.1007/s10334-024-01192-5

PubMed

39105950

More information

Latest update

10/7/2024