1 Laboratory for Functional and Metabolic Imaging (LIFMET), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
2 Center for Biomedical Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
J Cereb Blood Flow Metab. 2018 Oct;38(10):1701-1714. doi: 10.1177/0271678X17734101. Epub 2017 Oct 19.
In vivo C magnetic resonance spectroscopy (MRS) enables the investigation of cerebral metabolic compartmentation while, e.g. infusing C-labeled glucose. Metabolic flux analysis of C turnover previously yielded quantitative information of glutamate and glutamine metabolism in humans and rats, while the application to in vivo mouse brain remains exceedingly challenging. In the present study, C direct detection at 14.1 T provided highly resolved in vivo spectra of the mouse brain while infusing [1,6-C]glucose for up to 5 h. C incorporation to glutamate and glutamine C4, C3, and C2 and aspartate C3 were detected dynamically and fitted to a two-compartment model: flux estimation of neuron-glial metabolism included tricarboxylic acid cycle (TCA) flux in astrocytes (V = 0.16 ± 0.03 µmol/g/min) and neurons (V= 0.56 ± 0.03 µmol/g/min), pyruvate carboxylase activity (V = 0.041 ± 0.003 µmol/g/min) and neurotransmission rate (V = 0.084 ± 0.008 µmol/g/min), resulting in a cerebral metabolic rate of glucose (CMR) of 0.38 ± 0.02 µmol/g/min, in excellent agreement with that determined with concomitant F-fluorodeoxyglucose positron emission tomography (FDG PET).We conclude that modeling of neuron-glial metabolism in vivo is accessible in the mouse brain from C direct detection with an unprecedented spatial resolution under [1,6-C]glucose infusion.
在体内 C 磁共振波谱（MRS）能够在输注 C 标记的葡萄糖等情况下研究脑代谢区室。C 周转率的代谢通量分析以前提供了人类和大鼠谷氨酸和谷氨酰胺代谢的定量信息，而将其应用于体内小鼠大脑仍然极具挑战性。在本研究中，在 14.1 T 下进行的 C 直接检测提供了在输注 [1,6-C]葡萄糖长达 5 小时的情况下，高度分辨的小鼠脑体内光谱。谷氨酸和谷氨酰胺 C4、C3 和 C2 以及天冬氨酸 C3 的 C 掺入被动态检测并拟合到两室模型中：神经元-神经胶质代谢的通量估计包括三羧酸循环（TCA）在星形胶质细胞中的通量（V=0.16±0.03 µmol/g/min）和神经元（V=0.56±0.03 µmol/g/min）、丙酮酸羧化酶活性（V=0.041±0.003 µmol/g/min）和神经传递率（V=0.084±0.008 µmol/g/min），导致葡萄糖的脑代谢率（CMR）为 0.38±0.02 µmol/g/min，与伴随的 F-氟脱氧葡萄糖正电子发射断层扫描（FDG PET）确定的结果非常吻合。我们得出结论，从 [1,6-C]葡萄糖输注下具有前所未有的空间分辨率的 C 直接检测，体内神经元-神经胶质代谢的建模在小鼠大脑中是可行的。
