9.4-T MRI monitoring of early MASH progression and therapeutic response in a prefibrotic mouse model.

Abstract

OBJECTIVE: Early intervention in metabolic dysfunction-associated steatohepatitis (MASH) is critical to halt disease progression. However, noninvasive tools for monitoring early-stage MASH and therapeutic efficacy in preclinical models remain limited, impeding preclinical drug development. This study establishes an integrated approach using multiparametric magnetic resonance imaging (MRI) at 9.4&#x2009;T to dynamically track disease development and drug response in a prefibrotic MASH mouse model. MATERIALS AND METHODS: Mice were fed a high-fat and high-cholesterol diet (HFHCD) for 16 weeks to induce early MASH without fibrosis and treated with the anti-MASH drug semaglutide for 8 weeks after modeling. Longitudinal MRI assessments-including proton density fat fraction (PDFF),H magnetic resonance spectroscopy (MRS), Tmapping, and diffusion-weighted imaging (DWI)-were performed every 4 weeks and correlated with histopathology. RESULTS: Histology confirmed early MASH after 16 weeks, without fibrosis. All MRI parameters strongly correlated with histopathological scores. HFHCD feeding led to significant changes: PDFF, MRS-derived liver fat content (LFC), and Tvalues increased by 6.8-, 5.2-, and 2.5-fold, respectively, while apparent diffusion coefficient (ADC) decreased by 30% (p&#x2009;<&#x2009;0.001). Tand ADC also correlated with MRS-quantified saturated fatty acids. Semaglutide treatment effectively reversed these changes: PDFF decreased by 73%, LFC by 62%, Tby 46% (p&#x2009;<&#x2009;0.001), and ADC increased 1.4-fold (p&#x2009;=&#x2009;0.017) compared to the vehicle group. CONCLUSION: This work demonstrates multiparametric MRI as a powerful noninvasive platform for monitoring early MASH dynamics and treatment response. By enabling longitudinal assessment in a prefibrotic model, this approach accelerates translational research in MASH diagnosis and drug development. RELEVANCE STATEMENT: The established multiparametric MRI evaluation system provides a valuable noninvasive monitoring platform for preclinical early-stage MASH research, demonstrating significant potential to accelerate the translational progress in MASH diagnosis and drug development. KEY POINTS: A novel prefibrotic MASH model was established to assess early-stage MASH progression. Multiparametric MRI at 9.4&#x2009;T enables noninvasive, longitudinal monitoring of early MASH. Semaglutide-induced improvement in steatosis and inflammation can be monitored by multiparametric MRI.