Assessment of Rapid Hepatic Glycogen Synthesis in Humans Using Dynamic ¹³C Magnetic Resonance Spectroscopy

Carbon-13 magnetic resonance spectroscopy (MRS) following oral intake of ¹³C-labeled glucose is the gold standard for imaging glycogen metabolism in humans. However, the temporal resolution of previous studies has been >13 minutes. Here, we describe a high-sensitivity ¹³C MRS method for imaging hepatic glycogen synthesis with a temporal resolution of 1 minute or less. Nuclear magnetic resonance spectra were acquired from the liver of 3 healthy volunteers, using a ¹³C clamshell radiofrequency transmit and paddle-shaped array receive coils in a 3 Tesla magnetic resonance imaging system. Following a 15-minute baseline ¹³C MRS scan of the liver, [1-¹³C]-glucose was ingested and ¹³C MRS data were acquired for an additional 1-3 hours. Dynamic change of the hepatic glycogen synthesis level was analyzed by reconstructing the acquired MRS data with temporal resolutions of 30 seconds to 15 minutes. Plasma levels of ¹³C-labeled glucose and lactate were measured using gas chromatography-mass spectrometry. While not detected at baseline ¹³C MRS, [1-¹³C]-labeled α-glucose and β-glucose and glycogen peaks accumulated rapidly, beginning as early as ~2 minutes after oral administration of [1-¹³C]-glucose. The [1-¹³C]-glucose signals peaked at ~5 minutes, whereas [1-¹³C]-glycogen peaked at ~25 minutes after [1-¹³C]-glucose ingestion; both signals declined toward baseline levels over the next 1-3 hours. Plasma levels of ¹³C-glucose and ¹³C-lactate rose gradually, and approximately 20% of all plasma glucose and 5% of plasma lactate were ¹³C-labeled by 2 hours after ingestion. Conclusion: We observed rapid accumulation of hepatic [1-¹³C]-glycogen following orally administered [1-¹³C]-glucose, using a dynamic ¹³C MRS method with a temporal resolution of 1 minute or less. Commercially available technology allows high temporal resolution studies of glycogen metabolism in the human liver.