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

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.