Center for MR Research, University Children's Hospital, Steinwiesstrasse 75, CH-8032, Zürich, Switzerland.
Department of Nuclear Medicine, University Hospital Zürich, Rämistrasse 100, CH-8091, Zürich, Switzerland.
Neuroimage. 2019 Jan 1;184:826-833. doi: 10.1016/j.neuroimage.2018.10.017. Epub 2018 Oct 5.
Glutamate is the most abundant excitatory neurotransmitter in the human brain, but in vivo imaging of acute fluctuations in glutamatergic levels has not been well established. The purpose of this study was to examine acute changes in glutamate after stimulation with N-acetylcysteine (NAC) using a simultaneous positron emission tomography/magnetic resonance spectroscopy (PET/MRS) approach. Ten healthy adult males were examined in two scanning sessions, and 5g NAC was administered 1 h prior to one of the scan sessions. Simultaneous PET/MR data were acquired using an integrated 3T PET/MR scanner. Glutamate (Glu), glutamine (Gln), and glutamate + glutamine (Glx) levels were assessed from MRS data collected from the basal ganglia with PRESS and from the left prefrontal cortex with PRESS and MEGAPRESS, and mGluR5 binding (BP) was assessed from PET data collected with [F]PSS232. NAC administration was associated with a significant reduction in Glx and Gln in the basal ganglia spectra, and in Glx in the frontal MEGAPRESS spectra (p < 0.05); no differences in [F]PSS232 BP were observed with NAC, although a correlation between pre-/post-treatment Glx and baseline BPnd was found. The MRS-visible Glx signal is sensitive to acute fluctuations in glutamate. The change in Glx was mostly driven by a change in Gln, lending weight to the notion that Gln can provide a proxy marker for neurotransmitter/synaptic glutamate. [F]PSS232 binding is not sensitive to acute glutamate shifts independently, but was associated with the extent of glutamate liberation upon NAC stimulation.
谷氨酸是人类大脑中含量最丰富的兴奋性神经递质，但体内谷氨酸能水平的急性波动成像尚未得到很好的建立。本研究旨在使用正电子发射断层扫描/磁共振波谱（PET/MRS）方法检查 N-乙酰半胱氨酸（NAC）刺激后谷氨酸的急性变化。10 名健康成年男性在两次扫描中进行了检查，其中一次扫描前 1 小时给予 5g NAC。使用集成的 3T PET/MR 扫描仪采集同时的 PET/MR 数据。从基底节采集的 MRS 数据（使用 PRESS）和从左前额叶采集的 MRS 数据（使用 PRESS 和 MEGAPRESS）评估谷氨酸（Glu）、谷氨酰胺（Gln）和谷氨酸+谷氨酰胺（Glx）水平，使用 [F]PSS232 从 PET 数据评估 mGluR5 结合（BP）。NAC 给药与基底节光谱中 Glx 和 Gln 以及前额叶 MEGAPRESS 光谱中 Glx 显著降低相关（p<0.05）；尽管在治疗前/后 Glx 与基线 BPnd 之间发现相关性，但未观察到 NAC 对 [F]PSS232 BP 的差异。MRS 可见的 Glx 信号对谷氨酸的急性波动敏感。Glx 的变化主要是由 Gln 的变化驱动的，这进一步支持了 Gln 可以作为神经递质/突触谷氨酸的替代标志物的观点。[F]PSS232 结合本身对急性谷氨酸变化不敏感，但与 NAC 刺激时谷氨酸释放的程度有关。
