Proton Echo-Planar Spectroscopic Imaging of GABA, Glutamate/Glutamine at 4 Tesla

描述(申请人提供)：在这项建议中，我们将开发一种快速磁共振光谱成像(MRSI)序列，允许在临床合理的扫描时间(不到1小时)内获得最佳的GABA、谷氨酸(Glu)和谷氨酰胺(Gln)光谱。我们建议的方法将结合目前最先进的磁共振波谱(MRS)技术来在体内测量主要的抑制性神经递质GABA和主要的兴奋性神经递质Glu和Gln，以及快速和成熟的质子回声平面光谱成像(Pepsi)方法。这项新技术将把专门的MEGAPRESS GABA采集与J分辨率Glu/Gln采集相结合，在不到一小时的时间内产生这些代谢物在整个大脑中的实际代谢图像。这两种方法交叉使用的优点是在相同的时间过程中同时获得GABA、Glu和Gln，这是在急性药物挑战后跟踪这一神经递质系统活动所必需的一个重要方面。我们将首先进行一系列模型实验，以评估我们的序列在体外的性能，并验证我们的方法，评估我们的技术在重复测量中准确和精确跟踪不同浓度的GABA、Glu和Gln的能力。然后，我们将在健康志愿者的样本中评估我们的新技术在体内的表现，以评估我们在活着的大脑中测量代谢物的准确性和精密度。在我们的最后一项实验中，我们将在健康志愿者中进行药物挑战，以评估我们的方法在检测和量化药物引起的大脑中这些神经递质变化方面的临床实用性。这个项目完成后，我们将开发出一种重要的工具，用于在体内对GABA、Glu和Gln进行成像。从公共卫生的角度来看，这一工具将使我们能够通过绘制出这些化合物在大脑回路中的不同水平，进一步了解人类大脑中这个神经递质系统的工作原理。这将在精神病学研究和成瘾领域具有重要意义，以了解成瘾障碍中存在的神经化学异常。 与公众健康相关：该项目的目标是在我们的4特斯拉全身研究扫描仪上开发一种磁共振波谱协议，将差异编辑的优越GABA编辑特性与回声平面光谱成像的快速多体素覆盖相结合。这项技术将能够快速而准确地确定全球GABA在人脑中的分布，这可能成为研究GABA能药物在几个时间点的分布和吸收/洗出的药理学研究的工具。

DESCRIPTION (provided by applicant): In this proposal, we will develop a rapid magnetic resonance spectroscopic imaging (MRSI) sequence that will allow for the optimal acquisition of GABA, glutamate (Glu) and glutamine (Gln) spectra in a clinically reasonable scan-time (less than 1 hour). Our proposed method will combine the current, state-of-the-art magnetic resonance spectroscopy (MRS) techniques for the in vivo measurement of the primary inhibitory neurotransmitter GABA, as well as the primary excitatory neurotransmitter, Glu and Gln with the rapid and established method of proton echo-planar spectroscopic imaging (PEPSI). This novel technique will interleave the specialized MEGAPRESS GABA acquisition with the J-resolved Glu/Gln acquisition to yield an actual metabolic image of these metabolites across the brain in under an hour. The advantage of interleaving these two methods is for the simultaneous acquisition of GABA, Glu and Gln over the same time-course, a vital aspect which is necessary for tracking the activity of this neurotransmitter system after an acute drug challenge. We will first undertake a series of phantom experiments to assess the performance of our sequence in vitro and to validate our method, evaluating the ability of our technique to accurately and precisely track varying concentrations of GABA, Glu and Gln over repeated measures. We will then assess the performance of our novel technique in vivo in a sample of healthy volunteers to assess accuracy and precision in our metabolite measurements in living brains. In our final experiment, we will undertake a drug challenge in healthy volunteers to evaluate the clinical utility of our method in detecting and quantifying drug-induced changes in these neurotransmitters across the brain. Upon completion of this project, we will have developed an important tool for the imaging of GABA, Glu and Gln in vivo. From a public health standpoint, this tool would allow us to further understand the workings of this neurotransmitter system in the human brain by allowing us to map out the various levels of these compounds in brain circuits. This would have important implications in the field of psychiatric research and addiction to understand the neurochemical aberrations that exist in addictive disorders. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a magnetic resonance spectroscopy protocol on our 4 Tesla whole-body research scanner that combines the superior GABA-editing properties of difference-editing with the rapid multi- voxel coverage of echo-planar spectroscopic imaging. This technology will allow for the rapid yet accurate determination of global GABA distributions in the human brain which could potentially serve as a tool for pharmacology studies investigating the distribution and uptake/washout of GABAergic drugs over several time points.