Kjaergaard Uffe, Laustsen Christoffer, Nørlinger Thomas, Tougaard Rasmus S, Mikkelsen Emmeli, Qi Haiyun, Bertelsen Lotte B, Jessen Niels, Stødkilde-Jørgensen Hans
MR Research Centre, Aarhus University Hospital, Aarhus, Denmark.
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Physiol Rep. 2018 Dec;6(23):e13943. doi: 10.14814/phy2.13943.
Introduction of hyperpolarized magnetic resonance in preclinical studies and lately translation to patients provides new detailed in vivo information of metabolic flux in organs. Hyperpolarized magnetic resonance based on C enriched pyruvate is performed without ionizing radiation and allows quantification of the pyruvate conversion products: alanine, lactate and bicarbonate in real time. Thus, this methodology has a promising potential for in vivo monitoring of energetic alterations in hepatic diseases. Using C pyruvate, we investigated the metabolism in the porcine liver before and after intravenous injection of glucose. The overall mean lactate to pyruvate ratio increased significantly after the injection of glucose whereas the bicarbonate to pyruvate ratio was unaffected, representative of the levels of pyruvate entering the tricarboxylic acid cycle. Similarly, alanine to pyruvate ratio did not change. The increased lactate to pyruvate ratio over time showed an exponential correlation with insulin, glucagon and free fatty acids. Together, these data, obtained by hyperpolarized C magnetic resonance spectroscopy and by blood sampling, indicate a hepatic metabolic shift in glucose utilization following a glucose challenge. Our findings demonstrate the capacity of hyperpolarized C magnetic resonance spectroscopy for quantifying hepatic substrate metabolism in accordance with well-known physiological processes. When combined with concentration of blood insulin, glucagon and free fatty acids in the blood, the results indicate the potential of hyperpolarized magnetic resonance spectroscopy as a future clinical method for quantification of hepatic substrate metabolism.
超极化磁共振在临床前研究中的应用以及最近向患者的转化，为器官代谢通量提供了新的详细体内信息。基于碳富集丙酮酸的超极化磁共振无需电离辐射即可进行，并能实时定量丙酮酸转化产物：丙氨酸、乳酸和碳酸氢盐。因此，这种方法在体内监测肝脏疾病能量变化方面具有广阔的潜力。我们使用碳丙酮酸研究了猪肝脏在静脉注射葡萄糖前后的代谢情况。注射葡萄糖后，乳酸与丙酮酸的总体平均比值显著增加，而碳酸氢盐与丙酮酸的比值未受影响，这代表了进入三羧酸循环的丙酮酸水平。同样，丙氨酸与丙酮酸的比值也没有变化。随着时间推移，乳酸与丙酮酸比值的增加与胰岛素、胰高血糖素和游离脂肪酸呈指数相关。总之，通过超极化碳磁共振波谱和采血获得的这些数据表明，在葡萄糖刺激后肝脏在葡萄糖利用方面发生了代谢转变。我们的研究结果证明了超极化碳磁共振波谱根据众所周知的生理过程定量肝脏底物代谢的能力。当与血液中胰岛素、胰高血糖素和游离脂肪酸的浓度相结合时，结果表明超极化磁共振波谱作为未来定量肝脏底物代谢临床方法的潜力。
