Simultaneous monitoring of glycogen, creatine, and phosphocreatine in type II glycogen storage disease using saturation transfer MRI

Purpose

There is a need for non-invasive approaches to assess the progression of glycogen storage diseases (GSD). Here, we use saturation transfer (ST) MRI via relayed nuclear Overhauser effects (glycoNOE) to detect abnormal changes in muscle glycogen of a GSD II mouse model. In addition to glycogen, the energy metabolites phosphocreatine (PCr) and creatine (Cr) were studied to assess the muscle disease.

Methods

Water saturation (Z-spectra) and ¹H MRS were acquired at 9.4 T on the skeletal muscle of healthy control mice and homozygous acid $\alpha$-glucosidase (GAA) knock-out mice (ages of 2–48 weeks). The glycoNOE (−1 ppm), total creatine (tCr)* (+2 ppm, = a × [Cr] + b × [PCr]), and PCr (+2.5 ppm) from Z-spectra and the ratio between tCr and taurine signals (tCr/Tau) from ¹H MRS spectra were quantified by using multi-pool Lorentzian fitting methods. The concentrations of the metabolites were also measured via tissue assays.

Results

The postnatal GSD II mice (age <12 weeks) showed a continued accumulation of muscle glycoNOE signal. GlycoNOE in adult GSD II mice (age ≥12 weeks) reached a plateau, at a level above 400% of that in normal mice. PCr, tCr*, and tCr/Tau gradually decreased in GSD II mice during the postnatal stage, then stabilized at levels comparable to adult control, yet PCr in adult GSD II mice was lower than that in controls.

Conclusion

This study demonstrates that ST MRI of glycogen can provide in situ non-invasive biomarkers for GSD II disease progression, with the potential to study the progression and treatment response of GSDs.