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 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), 1H magnetic resonance spectroscopy (MRS), T2 mapping, 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 T2 values increased by 6.8-, 5.2-, and 2.5-fold, respectively, while apparent diffusion coefficient (ADC) decreased by 30% (p < 0.001). T2 and ADC also correlated with MRS-quantified saturated fatty acids. Semaglutide treatment effectively reversed these changes: PDFF decreased by 73%, LFC by 62%, T2 by 46% (p < 0.001), and ADC increased 1.4-fold (p = 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 <UnorderedList Mark="Bullet"> <ItemContent> A novel prefibrotic MASH model was established to assess early-stage MASH progression. </ItemContent> <ItemContent> Multiparametric MRI at 9.4 T enables noninvasive, longitudinal monitoring of early MASH. </ItemContent> <ItemContent> Semaglutide-induced improvement in steatosis and inflammation can be monitored by multiparametric MRI. </ItemContent> </UnorderedList> Graphical Abstract

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

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2026年5月6日

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Yuanyuan Li,
Yun Wu,
Gengxin Wang,
Yanmin Zheng,
Haiyang Tong,
Hongyi Yang,
Jin Yu,
Pan Shi,
Yong Zheng,
Li Zhou,
Xin Li,
Pei Lv,
Changlin Tian

摘要

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 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), ¹H magnetic resonance spectroscopy (MRS), T₂ mapping, 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 T₂ values increased by 6.8-, 5.2-, and 2.5-fold, respectively, while apparent diffusion coefficient (ADC) decreased by 30% (p < 0.001). T₂ and ADC also correlated with MRS-quantified saturated fatty acids. Semaglutide treatment effectively reversed these changes: PDFF decreased by 73%, LFC by 62%, T₂ by 46% (p < 0.001), and ADC increased 1.4-fold (p = 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 T enables noninvasive, longitudinal monitoring of early MASH.

Semaglutide-induced improvement in steatosis and inflammation can be monitored by multiparametric MRI.

Graphical Abstract