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

Carbon-13 magnetic resonance spectroscopy (MRS) following oral intake of (13)C-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 (13)C 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 (13)C clamshell radiofrequency transmit and paddle-shaped array receive coils in a 3 Tesla magnetic resonance imaging system. Following a 15-minute baseline (13)C MRS scan of the liver, [1-(13)C]-glucose was ingested and (13)C 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 (13)C-labeled glucose and lactate were measured using gas chromatography-mass spectrometry. While not detected at baseline (13)C MRS, [1-(13)C]-labeled alpha-glucose and beta-glucose and glycogen peaks accumulated rapidly, beginning as early as ~2 minutes after oral administration of [1-(13)C]-glucose. The [1-(13)C]-glucose signals peaked at ~5 minutes, whereas [1-(13)C]-glycogen peaked at ~25 minutes after [1-(13)C]-glucose ingestion; both signals declined toward baseline levels over the next 1-3 hours. Plasma levels of (13)C-glucose and (13)C-lactate rose gradually, and approximately 20% of all plasma glucose and 5% of plasma lactate were (13)C-labeled by 2 hours after ingestion. Conclusion: We observed rapid accumulation of hepatic [1-(13)C]-glycogen following orally administered [1-(13)C]-glucose, using a dynamic (13)C 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.