Liver glycogen represents an important physiological form of energy storage. It plays a key role in the regulation of
blood glucose concentrations, and dysregulations in
hepatic glycogen metabolism are linked to many diseases including diabetes and
insulin resistance. In this work, we develop, optimize, and validate a noninvasive protocol to measure
glycogen levels in isolated perfused mouse livers using chemical exchange saturation transfer (CEST) NMR spectroscopy. Model
glycogen solutions were used to determine optimal saturation pulse parameters which were then applied to intact perfused mouse livers of varying
glycogen content.
Glycogen measurements from serially acquired CEST Z-spectra of livers were compared with measurements from interleaved natural abundance (13)C NMR spectra. Experimental data revealed that CEST-based
glycogen measurements were highly correlated with (13)C NMR
glycogen spectra. Monte Carlo simulations were then used to investigate the inherent (i.e., signal-to-noise-based) errors in the quantification of
glycogen with each technique. This revealed that CEST was intrinsically more precise than (13)C NMR, although in practice may be prone to other errors induced by variations in experimental conditions. We also observed that the CEST signal from
glycogen in liver was significantly less than that observed from identical amounts in
solution. Our results demonstrate that CEST provides an accurate, precise, and readily accessible method to noninvasively measure
liver glycogen levels and their changes. Furthermore, this technique can be used to map
glycogen distributions via conventional
proton magnetic resonance imaging, a capability universally available on clinical and preclinical magnetic resonance imaging (MRI) scanners vs (13)C detection, which is limited to a small fraction of clinical-scale MRI scanners.