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研究在健康麻醉大鼠体内注射高极化 [1-13C]丙酮酸后,C 乳酸信号的起源。

Investigating the origin of the C lactate signal in the anesthetized healthy rat brain in vivo after hyperpolarized [1- C]pyruvate injection.

机构信息

Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Digital Health, Siemens Healthineers, Erlangen, Germany.

出版信息

NMR Biomed. 2024 Mar;37(3):e5073. doi: 10.1002/nbm.5073. Epub 2023 Nov 22.

Abstract

The goal of this study was to investigate the origin of brain lactate (Lac) signal in the healthy anesthetized rat after injection of hyperpolarized (HP) [1- C]pyruvate (Pyr). Dynamic two-dimensional spiral chemical shift imaging with flow-sensitizing gradients revealed reduction in both vascular and brain Pyr, while no significant dependence on the level of flow suppression was detected for Lac. These results support the hypothesis that the HP metabolites predominantly reside in different compartments in the brain (i.e., Pyr in the blood and Lac in the parenchyma). Data from high-resolution metabolic imaging of [1- C]Pyr further demonstrated that Lac detected in the brain was not from contributions of vascular signal attributable to partial volume effects. Additionally, metabolite distributions and kinetics measured with dynamic imaging after injection of HP [1- C]Lac were similar to Pyr data when Pyr was used as the substrate. These data do not support the hypothesis that Lac observed in the brain after Pyr injection was generated in other organs and then transported across the blood-brain barrier (BBB). Together, the presented results provide further evidence that even in healthy anesthetized rats, the transport of HP Pyr across the BBB is sufficiently fast to permit detection of its metabolic conversion to Lac within the brain.

摘要

本研究旨在探讨健康麻醉大鼠注射高极化(HP)[1- C]丙酮酸(Pyr)后脑内乳酸(Lac)信号的起源。采用带流动敏感梯度的二维螺旋化学位移成像显示,血管和脑内 Pyr 均减少,而 Lac 与流动抑制水平无明显相关性。这些结果支持以下假说,即 HP 代谢物主要存在于脑内的不同隔室(即 Pyr 在血液中,Lac 在实质中)。[1- C]Pyr 的高分辨率代谢成像数据进一步表明,脑内检测到的 Lac 并非源自由于部分容积效应而归因于血管信号的贡献。此外,在注射 HP [1- C]Lac 后进行动态成像测量的代谢物分布和动力学与 Pyr 数据相似,当使用 Pyr 作为底物时。这些数据不支持 Lac 在 Pyr 注射后在脑中观察到的假说,即它是在其他器官中产生的,然后穿过血脑屏障(BBB)运输到脑内。总之,所呈现的结果提供了进一步的证据,表明即使在健康麻醉的大鼠中,HP Pyr 穿过 BBB 的转运速度也足够快,可以在脑内检测到其代谢转化为 Lac。

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Measurement of Arterial Input Function in Hyperpolarized C Studies.超极化碳研究中动脉输入函数的测量。
Appl Magn Reson. 2012 Jul;43(1-2):289-297. doi: 10.1007/s00723-012-0348-3. Epub 2012 May 20.
8
Lactate as a fulcrum of metabolism.乳酸作为代谢的支点。
Redox Biol. 2020 Aug;35:101454. doi: 10.1016/j.redox.2020.101454. Epub 2020 Feb 9.

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