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

Area of Science:

• * Medical Imaging and Spectroscopy
• * Pharmacology and Drug Metabolism
• * Animal Models in Research

Background:

• * Dynamic contrast-enhanced MRI (DCE-MRI) is used to assess liver function in rats.
• * Previous studies indicate significant variability in DCE-MRI biomarkers across different research centers.

Purpose of the Study:

• * To identify the primary sources of variability in DCE-MRI liver function biomarkers in rats.
• * To compare data across different centers, field strengths, and time points.

Main Methods:

• * 13 substudies involving Wistar-Han rats were conducted across three facilities using 4.7T and 7T scanners.
• * DCE-MRI data were acquired using a 3D spoiled gradient echo sequence.
• * Analysis of variance was used to assess variability in hepatocellular uptake rate (K^trans) and biliary excretion rate (k_bh).

Main Results:

• * Significant between-substudy differences were observed for both K^trans (31%) and k_bh (43%).
• * Between-centre variability accounted for the largest portion of data variation (K^trans: 44.9%, k_bh: 50.9%).
• * Within-subject repeatability was better for k_bh (8%) than K^trans (25%).

Conclusions:

• * Between-centre bias, stemming from hardware, preparation, and operator factors, is the main driver of variability in rat liver DCE-MRI.
• * Biological differences between subjects also contribute significantly to variability.
• * Reducing these errors is essential for improving the sensitivity of DCE-MRI in detecting subtle drug effects.