Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease
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 origi...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-49971-9 |
| _version_ | 1827399518255054848 |
|---|---|
| author | Marlena Rohm Gabriele Russo Xavier Helluy Martijn Froeling Vincent Umathum Nicolina Südkamp Denise Manahan-Vaughan Robert Rehmann Johannes Forsting Frank Jacobsen Andreas Roos Yoon Shin Anne Schänzer Matthias Vorgerd Lara Schlaffke |
| author_facet | Marlena Rohm Gabriele Russo Xavier Helluy Martijn Froeling Vincent Umathum Nicolina Südkamp Denise Manahan-Vaughan Robert Rehmann Johannes Forsting Frank Jacobsen Andreas Roos Yoon Shin Anne Schänzer Matthias Vorgerd Lara Schlaffke |
| author_sort | Marlena Rohm |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T19:47:12Z |
| format | Article |
| id | doaj.art-3bd7a96d0a32465b92df1d3a2ab6a9e5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T19:47:12Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3bd7a96d0a32465b92df1d3a2ab6a9e52023-12-24T12:17:16ZengNature PortfolioScientific Reports2045-23222023-12-0113111210.1038/s41598-023-49971-9Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe diseaseMarlena Rohm0Gabriele Russo1Xavier Helluy2Martijn Froeling3Vincent Umathum4Nicolina Südkamp5Denise Manahan-Vaughan6Robert Rehmann7Johannes Forsting8Frank Jacobsen9Andreas Roos10Yoon Shin11Anne Schänzer12Matthias Vorgerd13Lara Schlaffke14Department of Neurology, Berufsgenossenschaftliches-University Hospital Bergmannsheil gGmbH, Ruhr-University BochumDepartment of Neurophysiology, Medical Faculty, Ruhr-University BochumDepartment of Neurophysiology, Medical Faculty, Ruhr-University BochumDepartment of Radiology, University Medical Centre UtrechtInstitute of Neuropathology, Justus Liebig UniversityDepartment of Neurology, Berufsgenossenschaftliches-University Hospital Bergmannsheil gGmbH, Ruhr-University BochumDepartment of Neurophysiology, Medical Faculty, Ruhr-University BochumDepartment of Neurology, Berufsgenossenschaftliches-University Hospital Bergmannsheil gGmbH, Ruhr-University BochumDepartment of Neurology, Berufsgenossenschaftliches-University Hospital Bergmannsheil gGmbH, Ruhr-University BochumDepartment of Neurology, Berufsgenossenschaftliches-University Hospital Bergmannsheil gGmbH, Ruhr-University BochumDepartment of Neurology, Berufsgenossenschaftliches-University Hospital Bergmannsheil gGmbH, Ruhr-University BochumMolecular Genetic and Metabolism LaboratoryInstitute of Neuropathology, Justus Liebig UniversityDepartment of Neurology, Berufsgenossenschaftliches-University Hospital Bergmannsheil gGmbH, Ruhr-University BochumDepartment of Neurology, Berufsgenossenschaftliches-University Hospital Bergmannsheil gGmbH, Ruhr-University BochumAbstract 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.https://doi.org/10.1038/s41598-023-49971-9 |
| spellingShingle | Marlena Rohm Gabriele Russo Xavier Helluy Martijn Froeling Vincent Umathum Nicolina Südkamp Denise Manahan-Vaughan Robert Rehmann Johannes Forsting Frank Jacobsen Andreas Roos Yoon Shin Anne Schänzer Matthias Vorgerd Lara Schlaffke Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease Scientific Reports |
| title | Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease |
| title_full | Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease |
| title_fullStr | Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease |
| title_full_unstemmed | Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease |
| title_short | Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease |
| title_sort | muscle diffusion mri reveals autophagic buildup in a mouse model for pompe disease |
| url | https://doi.org/10.1038/s41598-023-49971-9 |
| work_keys_str_mv | AT marlenarohm musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT gabrielerusso musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT xavierhelluy musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT martijnfroeling musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT vincentumathum musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT nicolinasudkamp musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT denisemanahanvaughan musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT robertrehmann musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT johannesforsting musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT frankjacobsen musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT andreasroos musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT yoonshin musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT anneschanzer musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT matthiasvorgerd musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease AT laraschlaffke musclediffusionmrirevealsautophagicbuildupinamousemodelforpompedisease |