Marlena Rohm (Bochum / DE), Gabriele Russo (Bochum / DE), Xavier Helluy (Bochum / DE), Dr. jur. Martijn Froeling (Utrecht / NL), Denise Manahan-Vaughan (Bochum / DE), Prof. Dr. med Anne Schänzer (Gießen / DE), Prof. Dr. Matthias Vorgerd (Bochum / DE), Dr. rer. nat Lara Schlaffke (Bochum / DE)
Abstract-Text (inkl. Referenzen)
Introduction: In Pompe disease a mutation in the α-Glucosidase enzyme leads to accumulation of glycogen and autophagosomes. Previously, we reported a reduction in diffusion in skeletal muscles using magnetic resonance imaging (MRI) in adult Pompe patients. To identify histopathological correlations, the same quantitative MRI protocol was translated to a mouse model of Pompe disease.
Methods: The hind limb of pre-symptomatic GAA6neo/6neo and wildtype mice at the age of one to eight month was scanned on a monthly basis using Dixon, diffusion tensor imaging (DTI) and T2-mapping sequences. In addition, detailed morphologic characterization of muscle pathology including glycogen accumulation and autophagic marker were carried out to correlate muscle pathology with DTI.
Results: In GAA6neo/6neo mice altered diffusion was significant and correlates to autophagic buildup, but not with glycogen or lysosomal accumulation. No fat infiltration or inflammation was seen with MRI.
Discussion: The progressive changes in diffusion detected by means of MRI in the hind limb in different developmental stages of Pompe mice corresponded well with the abundance of autophagosomes. This indicated in turn, that MRI can serve as an effective non-invasive tool to reveal disease progression in Pompe disease, especially in early stages of disease pathogenesis.