Detection of Altered Muscle Glycogen- and NOE-Weighted CEST MRI Signals in an Acid Alpha-Glucosidase-Deficient Mouse...

Chemical exchange saturation transfer (CEST) MRI is a non-invasive imaging technique that detects dilute labile protons with enhanced sensitivity, aiding in the assessment of tissue properties. This study aimed to evaluate the diagnostic usefulness of CEST MRI in acid alpha-glucosidase knockout (GAAKO) mice, a model of Pompe disease characterized by lysosomal glycogen accumulation in muscles.

We conducted multiparametric MRI at a 7 T Bruker MRI scanner, including T1 and T2 relaxation mapping and densely sampled CEST Z-spectral acquisition, on adult GAAKO and wild-type control mice. Multi-pool CEST signals were obtained from spinlock model-based fitting of the quasi-steady-state reconstructed Z-spectrum. Using the gold-standard muscle glycogen assay as a biomarker of disease burden, we analyzed the correlation between relaxation and CEST signals and tissue glycogen levels.

Biochemical glycogen assays of excised muscle samples confirmed significantly elevated glycogen levels in GAAKO mice (556 ± 125 mg/kg) compared to wild-type controls (60 ± 22 mg/kg). Among MRI-derived parameters, glycogen and near-resonance nuclear Overhauser enhancement (NOE) signals showed significant differences between control and GAAKO mice. Importantly, glycogen-weighted CEST (R² = 0.45, p < 0.0001) and NOE signal at -1.2 ppm (R² = 0.57, p < 0.0001) demonstrated significant correlations with glycogen assay measurement.

Multi-pool CEST MRI metrics show potential for characterizing muscle pathology in GAAKO mice. These findings support using CEST MRI to monitor tissue glycogen levels non-invasively.