Monitoring muscle glycogen accumulation in the GAAKO mouse model of Pompe disease with glycogen CEST (GlyCEST) MRI

Motivation: Pompe disease is an autosomal recessive metabolic disorder that is characterized by a deficiency of the lysosomal enzyme alpha-glucosidase (GAA), resulting in massive glycogen deposition in muscle. It helps to develop advanced CEST MRI to help manage Pompe disease. Goal(s): We aimed to develop and test quantitative glycogen CEST (GlyCEST) MRI for non-invasive monitoring of disease progression in GAAKO mice. Approach: We performed longitudinal GlyCEST scans in wild-type and GAAKO mice and tested the correlation between QUASS-boosted quantitative glycogen MRI with glycogen assay. Results: GlyCEST MRI provides a surrogate MRI biomarker that significantly correlates with the muscle glycogen biochemical assay. Impact: GlyCEST is promising to monitor glycogen levels in Pompe mice in real-time non-invasively and is potentially valuable for monitoring treatment response and ultimately clinical translation.