Stender Stefan, Zaha Vlad G, Malloy Craig R, Sudderth Jessica, DeBerardinis Ralph J, Park Jae Mo
Department of Molecular Genetics University of Texas Southwestern Medical Center Dallas TX.
Department of Clinical Biochemistry Rigshospitalet Copenhagen Denmark.
Hepatol Commun. 2020 Jan 4;4(3):425-433. doi: 10.1002/hep4.1458. eCollection 2020 Mar.
Carbon-13 magnetic resonance spectroscopy (MRS) following oral intake of 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 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 C clamshell radiofrequency transmit and paddle-shaped array receive coils in a 3 Tesla magnetic resonance imaging system. Following a 15-minute baseline C MRS scan of the liver, [1-C]-glucose was ingested and 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 C-labeled glucose and lactate were measured using gas chromatography-mass spectrometry. While not detected at baseline C MRS, [1-C]-labeled α-glucose and β-glucose and glycogen peaks accumulated rapidly, beginning as early as ~2 minutes after oral administration of [1-C]-glucose. The [1-C]-glucose signals peaked at ~5 minutes, whereas [1-C]-glycogen peaked at ~25 minutes after [1-C]-glucose ingestion; both signals declined toward baseline levels over the next 1-3 hours. Plasma levels of C-glucose and C-lactate rose gradually, and approximately 20% of all plasma glucose and 5% of plasma lactate were C-labeled by 2 hours after ingestion. We observed rapid accumulation of hepatic [1-C]-glycogen following orally administered [1-C]-glucose, using a dynamic 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.
口服摄入碳-13标记的葡萄糖后进行碳-13磁共振波谱（MRS）检查是人体糖原代谢成像的金标准。然而，以往研究的时间分辨率大于13分钟。在此，我们描述了一种高灵敏度的碳MRS方法，用于肝脏糖原合成成像，时间分辨率为1分钟或更短。在3特斯拉磁共振成像系统中，使用碳蛤壳形射频发射线圈和桨状阵列接收线圈，从3名健康志愿者的肝脏获取核磁共振谱。在对肝脏进行15分钟的基线碳MRS扫描后，摄入[1-碳]-葡萄糖，并在另外1至3小时内获取碳MRS数据。通过以30秒至15分钟的时间分辨率重建采集到的MRS数据，分析肝脏糖原合成水平的动态变化。使用气相色谱-质谱法测量血浆中碳标记的葡萄糖和乳酸水平。在基线碳MRS检查中未检测到，但[1-碳]-标记的α-葡萄糖、β-葡萄糖和糖原峰迅速积累，最早在口服[1-碳]-葡萄糖后约2分钟开始。[1-碳]-葡萄糖信号在约5分钟时达到峰值，而[1-碳]-糖原在摄入[1-碳]-葡萄糖后约25分钟达到峰值；在接下来的1至3小时内，两个信号均降至基线水平。血浆中碳-葡萄糖和碳-乳酸水平逐渐升高，摄入后2小时，所有血浆葡萄糖的约20%和血浆乳酸的5%被碳标记。我们使用时间分辨率为1分钟或更短的动态碳MRS方法，观察到口服[1-碳]-葡萄糖后肝脏[1-碳]-糖原迅速积累。商业可用技术允许对人体肝脏糖原代谢进行高时间分辨率研究。
