Rothman D L, Novotny E J, Shulman G I, Howseman A M, Petroff O A, Mason G, Nixon T, Hanstock C C, Prichard J W, Shulman R G
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9603-6. doi: 10.1073/pnas.89.20.9603.
A limitation of previous methods for studying human brain glucose metabolism, such as positron emission tomography, is that metabolic steps beyond glucose uptake cannot be studied. Nuclear magnetic resonance (NMR) has the advantage of allowing the nondestructive measurement of 13C distribution in specific carbon positions of metabolites. In this study 1H-[13C] NMR spectroscopy in conjunction with volume localization was used to measure the rate of incorporation of 13C isotope from infused enriched [1-13C]glucose to human brain [4-13C]glutamate. In three studies C4 glutamate turnover time constants of 25, 20, and 17 min were measured in a 21-cm3 volume centered in the region of the visual cortex. Based on an analysis of spectrometer sensitivity the spatial resolution of the method can be improved to < 4 cm3. In conjunction with metabolic modeling and other NMR measurements this method can provide a measure of regional rates of the brain tricarboxylic acid cycle and other metabolic pathways.
以往用于研究人类大脑葡萄糖代谢的方法,如正电子发射断层扫描,存在一个局限性,即无法研究葡萄糖摄取之外的代谢步骤。核磁共振(NMR)具有能够对代谢物特定碳位置的13C分布进行无损测量的优势。在本研究中,1H-[13C]核磁共振波谱结合体积定位技术,用于测量从注入的富集[1-13C]葡萄糖到人类大脑[4-13C]谷氨酸中13C同位素的掺入率。在三项研究中,在以视觉皮层区域为中心的21立方厘米体积内,测量到C4谷氨酸周转时间常数分别为25、20和17分钟。基于对光谱仪灵敏度的分析,该方法的空间分辨率可提高到<4立方厘米。结合代谢建模和其他核磁共振测量,该方法可以提供大脑三羧酸循环和其他代谢途径区域速率的测量值。