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Quantifying normal human brain metabolism using hyperpolarized [1-C-13] pyruvate and magnetic resonance imaging

机译:使用超极化的[1-C-13]丙酮酸和磁共振成像来定量正常人脑代谢

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摘要

Hyperpolarized C-13 Magnetic Resonance Imaging (C-13-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1-C-13]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of C-13 images demonstrated C-13-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (k(PL)) for exchange of the hyperpolarized C-13 label between [1-C-13]pyruvate and the endogenous lactate pool was 0.012 +/- 0.006 s(-1) and the apparent rate constant (k(PB)) for the irreversible flux of [1-C-1(3)]pyruvate to [C-13]bicarbonate was 0.002 +/- 0.002 s(-1). Imaging also revealed that [1-C-13]pyruvate, [1-C-13] lactate and [C-13]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1-C-13]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies.
机译:超极化的C-13磁共振成像(C-13-MRI)在体内提供了一个高度敏感的工具来探测组织代谢,并在最近被翻译成临床研究。我们报告在健康人志愿者首次大脑的静脉注射超极化[1-C-13]丙酮酸脑代谢。 C-13的图像的动态采集表现出既乳酸盐和碳酸氢盐的C-13标记,通过胞质乳酸脱氢酶和丙酮酸线粒体分别脱氢酶催化。这表明,这两种酶在生物体内可探测在一个完整的血脑屏障的存在:用于之间的超极化的C-13标记的交换所测量的表观汇率常数(k(PL))[1-C-13]丙酮酸和内源性乳酸池为0.012 +/- 0.006秒(-1),对[1-C-1(3)]丙酮酸至[C-13]的不可逆去磁的表观速率常数(k(PB))碳酸氢盐为0.002 +/- 0.002秒(-1)。成像还透露,[1-C-13]丙酮酸盐,[1-C-13]乳酸盐和[C-13]碳酸氢盐是在灰质显著更高相比白质。成像超极化[1-C-13]丙酮酸和后续量化正常脑组织代谢,对今后的研究解释病理性脑代谢的重要意义。

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