Related Experiment Video
Updated: Jul 7, 2025
Molecular Imaging to Target Transplanted Muscle Progenitor Cells
Published on: March 27, 2013
Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease
Marlena Rohm1,2, Gabriele Russo3, Xavier Helluy3,4
1Department of Neurology, Berufsgenossenschaftliches-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
Abstract:
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 (Gaa6neo/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.
Insights
Diffusion MRI detects early muscle microstructural changes in Pompe disease mouse models. These changes correlate with autophagic buildup and fiber diameter, indicating diffusion MRI
Area of Science:
- Neuromuscular Disorders
- Quantitative Muscle MRI
- Diffusion MRI
Background:
- Quantitative muscle MRI (qMRI) is crucial for evaluating neuromuscular disorders.
- Histopathological changes driving qMRI alterations in Pompe disease are not fully understood.
- Early diffusion MRI changes in non-fat infiltrated muscles were observed in Pompe patients.
Purpose of the Study:
- To investigate the histopathological basis of diffusion MRI changes in Pompe disease.
- To correlate diffusion MRI findings with lysosomal and autophagic markers in a longitudinal mouse model.
- To assess the utility of qMRI in detecting early disease-related microstructural alterations.
Main Methods:
- Longitudinal study using Pompe (Gaa6neo/6neo) and wildtype mice (1-8 months).
- Monthly 7T MRI scans including diffusion MRI, T2-mapping, and Dixon water-fat imaging.
- Immunofluorescence analysis of quadriceps for lysosomal and autophagic markers, correlated with MRI data.
Main Results:
- No significant differences in fat fraction or water-T2 between Pompe and wildtype mice.
- Pompe mice showed increased fractional anisotropy and decreased mean diffusivity (MD) and radial diffusivity (RD).
- Reduced RD and MD correlated negatively with autophagic markers and muscle fiber diameter.
Conclusions:
- Diffusion MRI reveals microstructural changes in presymptomatic Pompe mouse muscles without fat infiltration.
- These diffusion changes are linked to autophagic buildup and muscle fiber diameter alterations.
- Diffusion MRI is a valuable tool for detecting early, non-fat-infiltrated muscle changes in Pompe disease, reflecting autophagic processes.
