MRI-based assessment of liver perfusion and hepatocyte injury in the murine model of acute hepatitis

Abstract

ObjectiveTo assess alterations in perfusion and liver function in the concanavalin A (ConA)-induced mouse model of acute liver failure (ALF) using two magnetic resonance imaging (MRI)-based methods: dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA contrast agent and arterial spin labelling (ASL).Materials and methodsBALB/c mice were studied using a 9.4 T MRI system. The IntraGateFLASHTM and FAIR-EPI pulse sequences were used for optimum mouse abdomen imaging.ResultsThe average perfusion values for the liver of the control and ConA group were equal to 245 ± 20 and 200 ± 32 ml/min/100 g (p = 0.008, respectively). DCE-MRI showed that the time to the peak of the image enhancement was 6.14 ± 1.07 min and 9.72 ± 1.69 min in the control and ConA group (p < 0.001, respectively), while the rate of the contrast wash-out in the control and ConA group was 0.037 ± 0.008 and 0.021 ± 0.008 min−1 (p = 0.004, respectively). These results were consistent with hepatocyte injury in the ConA-treated mice as confirmed by histopathological staining.ConclusionsBoth the ASL and DCE-MRI techniques represent a reliable methodology to assess alterations in liver perfusion and hepatocyte integrity in murine hepatitis.

Dynamic Contrast-Enhanced MRI in the Abdomen of Mice with High Temporal and Spatial Resolution Using Stack-of-Stars Sampling and KWIC Reconstruction

“…Several DCE studies of the abdominal organs in mice have been previously reported including examination of pancreas [ 41 , 42 , 43 , 44 ], placenta [ 45 , 46 ], kidney [ 24 , 47 ] and liver [ 2 , 48 , 49 , 50 , 51 ]. Most of these studies employed full Cartesian sampling for acquisition of the dynamic data.…”

“…However, the resulting dynamic data are often corrupted by motion artifacts. A variety of approaches for minimization of motion artifacts have also been proposed including securing the tissue of interest with a plastic platen [ 41 ], prospective gating [ 18 ], non-affine image registration [ 42 ] and use of navigator echoes [ 49 ]. Though application of these methods generally reduces the frequency of occurance of motion artifacts, some data corruptoin persists.…”

Lumped Parameter Liver Simulation to Predict Acute Hemodynamic Alterations Following Partial Resections

“…In future studies, we plan to validate predictions of our model against post-operative clinical measurements. Water-fat quantification techniques using MRI are available to measure tissue perfusion with quantitative characterization of parenchymal and microcirculatory changes (66) and to study the extent of liver damage (66, 67).…”

Preclinical models of acute liver failure: a comprehensive review

“…ConA for the induction of ALF is well described in mice, though not well characterized in other animal models. ConA is dosed between 8–35 mg/kg IV, dissolved in sterile PBS or NS (it is unknown whether it can be administered with the same effect IP) ( Byk et al, 2016 ; Tadokoro et al, 2017 ). Dose finding experiments are recommended prior to beginning experiments, as its efficacy is known to vary by batch.…”