Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease

  • Quantitative muscle MRI is increasingly important in the non-invasive evaluation of neuromuscular disorders and their progression. Underlying histopathotological alterations, leading to changes in qMRI parameters are incompletely unraveled. Early microstructural differences of unknown origin reflected by Diffusion MRI in non-fat infiltrated muscles were detected in Pompe patients. This study employed a longitudinal approach with a Pompe disease mouse model to investigate the histopathological basis of these changes. Monthly scans of Pompe (Gaa\(^{6neo/6neo}\)) and wildtype mice (age 1–8 months) were conducted using diffusion MRI, T2-mapping, and Dixon-based water-fat imaging on a 7 T scanner. Immunofluorescence studies on quadriceps muscles were analyzed for lysosomal accumulations and autophagic buildup and correlated with MRI outcome measures. Fat fraction and water-T2 did not differ between groups and remained stable over time. In Pompe mice, fractional anisotropy increased, while mean diffusivity (MD) and radial diffusivity (RD) decreased in all observed muscles. Autophagic marker and muscle fibre diameter revealed significant negative correlations with reduced RD and MD, while lysosomal marker did not show any change or correlation. Using qMRI, we showed diffusion changes in muscles of presymptomatic Pompe mice without fat-infiltrated muscles and correlated them to autophagic markers and fibre diameter, indicating diffusion MRI reveals autophagic buildup.

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Author:Marlena RohmORCiDGND, Gabriele RussoORCiDGND, Xavier HelluyGND, Martijn FroelingORCiDGND, Vincent UmathumGND, Nicolina Nathalie SüdkampGND, Denise Manahan-VaughanORCiDGND, Robert RehmannORCiDGND, Johannes ForstingORCiDGND, Frank JacobsenGND, Andreas RoosORCiDGND, Yoon ShinGND, Anne SchänzerGND, Matthias VorgerdORCiDGND, Lara SchlaffkeORCiDGND
Parent Title (English):Scientific reports
Publisher:Springer Nature
Place of publication:Berlin
Document Type:Article
Date of Publication (online):2024/04/15
Date of first Publication:2023/12/20
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
Issue:Artikel 22822
First Page:22822-1
Last Page:22822-12
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Neurologische Universitätsklinik und Poliklinik
Heimer-Institut für Muskelforschung am Bergmannsheil
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International