Using endogenous glycogen as relaxation agent for imaging liver metabolism by MRI

Glycogen plays essential roles in glucose metabolism. Imaging glycogen in the liver, the major glycogen reservoir in the body, may shed new light on many metabolic disorders. ¹³C magnetic resonance spectroscopy (MRS) has become the mainstream method for monitoring glycogen in the body. However, the equipment of special hardware to standard clinical magnetic resonance imaging (MRI) scanners limits its clinical applications. Herein, we utilized endogenous glycogen as a T ₂-based relaxation contrast agent for imaging glycogen metabolism in the liver in vivo. The in vitro results demonstrated that the transverse relaxation rate of glycogen strongly correlates with the concentration, pH, and field strength. Based on the Swift-Connick theory, we characterized the exchange property of glycogen and measured the exchange rate of glycogen as 31,847 Hz at 37 °C. Besides, the viscosity and echo spacing showed no apparent effect on the transverse relaxation rate. This unique feature enables visualization of glycogen signaling in vivo through T ₂-weighted MRI. Two hours-post intraperitoneal injection of glucagon, a clinical drug to promote glycogenolysis and gluconeogenesis, the signal intensity of the mice's liver increased by 1.8 times from the T ₂-weighted imaging experiment due to the decomposition of glycogen. This study provides a convenient imaging strategy to non-invasively investigate glycogen metabolism in the liver, which may find clinical applications in metabolic diseases.