Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging

Abstract

Background: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized.

Purpose: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features.

Animal model: Established PBDL models.

Population: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group.

Field strength/sequence: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging.

Assessment: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D^* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system.

Statistical tests: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant.

Results: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2^* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956.

Data conclusion: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation.

Level of evidence: 1 TECHNICAL EFFICACY: Stage 2.

Keywords: bile duct; fibrosis; liver; magnetic resonance imaging; mice.