Background: To facilitate translational drug development for liver fibrosis, preclinical trials need to be run in\nparallel with clinical research. Liver function estimation by gadoxetate-enhanced dynamic contrast-enhanced MRI\n(DCE-MRI) is being established in clinical research, but still rarely used in preclinical trials. We aimed to evaluate\nfeasibility of DCE-MRI indices as translatable biomarkers in a liver fibrosis animal model.\nMethods: Liver fibrosis was induced in Sprague-Dawley rats by thioacetamide (200 mg, 150 mg, and saline for the\nhigh-dose, low-dose, and control groups, respectively). Subsequently, DCE-MRI was performed to measure: relative\nliver enhancement at 3-min (RLE-3), RLE-15, initial area-under-the-curve until 3-min (iAUC-3), iAUC-15, and\nmaximum-enhancement (Emax). The correlation coefficients between these MRI indices and the histologic collagen\narea, indocyanine green retention at 15-min (ICG-R15), and shear wave elastography (SWE) were calculated.\nDiagnostic performance to diagnose liver fibrosis was also evaluated by receiver-operating-characteristic (ROC)\nanalysis.\nResults: Animal model was successful in that the collagen area of the liver was the largest in the high-dose group,\nfollowed by the low-dose group and control group. The correlation between the DCE-MRI indices and collagen\narea was high for iAUC-15, Emax, iAUC-3, and RLE-3 but moderate for RLE-15 (r, - 0.81, - 0.81, - 0.78, - 0.80, and -\n0.51, respectively). The DCE-MRI indices showed moderate correlation with ICG-R15: the highest for iAUC-15,\nfollowed by iAUC-3, RLE-3, Emax, and RLE-15 (r, - 0.65, - 0.63, - 0.62, - 0.58, and - 0.56, respectively). The correlation\ncoefficients between DCE-MRI indices and SWE ranged from - 0.59 to - 0.28. The diagnostic accuracy of RLE-3,\niAUC-3, iAUC-15, and Emax was 100% (AUROC 1.000), whereas those of RLE-15 and SWE were relatively low\n(AUROC 0.777, 0.848, respectively).\nConclusion: Among the gadoxetate-enhanced DCE-MRI indices, iAUC-15 and iAUC-3 might be bidirectional\ntranslatable biomarkers between preclinical and clinical research for evaluating histopathologic liver fibrosis and\nphysiologic liver functions in a non-invasive manner.
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