Mapping glycogen accumulation and treatment effect in Pompe disease with saturation transfer MRI.

Abstract

Pompe disease is a glycogen storage disease caused by the impaired breakdown of glycogen in lysosomes, leading to abnormal glycogen accumulation in tissue. Here we use glycogen nuclear Overhauser effect (glycoNOE) MRI to detect glycogen levels in skeletal muscle in a mouse model of Pompe disease. Moreover, we evaluated if glycoNOE MRI could detect changes in glycogen load after enzyme replacement therapy. The results show that glycoNOE MRI can distinguish between Pompe mice and wildtype controls. Furthermore, the technique detected treatment-dependent changes in muscle glycoNOE signals, which were validated with ex vivo biochemical assays. To demonstrate potential human translation, glycoNOE MRI was applied to two Pompe patients and revealed elevated glycogen levels in patients compared to healthy controls.