Visco-Elastic Parameters at Three-Dimensional MR Elastography for Diagnosing Non-Alcoholic Steatohepatitis and Substantial Fibrosis in Mice

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide and is a growing cause of liver cirrhosis and cancer. The performance of the magnetic resonance elastography (MRE) visco-elastic parameters in diagnosing progressive forms of NAFLD, including nonalcoholic steatohepatitis (NASH) and substantial fibrosis (F ≥ 2), needs to be clarified.

Purpose: To assess the value of three-dimensional MRE visco-elastic parameters as markers of NASH and substantial fibrosis in mice with NAFLD.

Study type: Prospective.

Animal model: Two mouse models of NAFLD were induced by feeding with high fat diet or high fat, choline-deficient, amino acid-defined diet.

Field strength/sequence: 7T/multi-slice multi-echo spin-echo MRE at 400 Hz with motion encoding in the three spatial directions.

Assessment: Hepatic storage and loss moduli were calculated. Histological analysis was based on the NASH Clinical Research Network criteria.

Statistical tests: Mann-Whitney, Kruskal-Wallis tests, Spearman rank correlations and multiple regressions were used. Diagnostic performance was assessed with areas under the receiver operating characteristic curves (AUCs). P value <0.05 was considered significant.

Results: Among the 59 mice with NAFLD, 21 had NASH and 20 had substantial fibrosis (including 8 mice without and 12 mice with NASH). The storage and loss moduli had similar moderate accuracy for diagnosing NASH with AUCs of 0.67 and 0.66, respectively. For diagnosing substantial fibrosis, the AUC of the storage modulus was 0.73 and the AUC of the loss modulus was 0.81, indicating good diagnostic performance. Using Spearman correlations, histological fibrosis, inflammation and steatosis, but not ballooning, were significantly correlated with the visco-elastic parameters. Using multiple regression, fibrosis was the only histological feature independently associated with the visco-elastic parameters.

Conclusion: MRE in mice with NAFLD suggests that the storage and loss moduli have good diagnostic performance for detecting progressive NAFLD defined as substantial fibrosis rather than NASH.

Evidence level: 1 TECHNICAL EFFICACY STAGE: 2.

Keywords: liver fibrosis; liver inflammation; liver magnetic resonance elastography; nonalcoholic fatty liver disease; visco-elasticity.