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

4 特斯拉下 GABA、谷氨酸/谷氨酰胺的质子回波平面光谱成像

• 批准号: 8100239
• 负责人: JOHN E JENSEN
• 金额: $ 17.49万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100239
• 关键词: Acute; Address; Blinded; Brain; Brain region; Clinical; Cocaine; Cohort Studies; Collection; Data; Detection; Equilibrium; Functional disorder; Glutamates; Glutamine; Goals; Hour; Human; Human Volunteers; Image; Imaging Device; In Vitro; Intravenous; Life; Literature; Magnetic Resonance Spectroscopy; Maps; Measurement; Measures; Metabolic; Methods; Midazolam; Modality; Neuraxis; Neurologic; Neurotransmitters; Participant; Performance; Pharmaceutical Preparations; Pharmacology; Preparation; Property; Protocols documentation; Protons; Psyche structure; Public Health; Regression Analysis; Research; Research Personnel; Resources; Sampling; Scanning; Series; Specificity; Structure; Substance abuse problem; System; Techniques; Technology; Testing; Time; Tissues; Work; addiction; base; cost; experience; gamma-Aminobutyric Acid; gray matter; healthy volunteer; imaging modality; in vivo; interest; magnetic resonance spectroscopic imaging; meetings; neurochemistry; neuropathology; novel; psychopharmacologic; public health relevance; research study; sound; spectroscopic imaging; success; time use; tool; two-dimensional; uptake; volunteer; white matter

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.

描述（由申请人提供）：在本提案中，我们将开发一种快速磁共振波谱成像 (MRSI) 序列，该序列将允许在临床合理的扫描时间（不到 1 小时）内最佳采集 GABA、谷氨酸 (Glu) 和谷氨酰胺 (Gln) 波谱。我们提出的方法将结合当前最先进的磁共振波谱 (MRS) 技术，用于体内测量主要抑制性神经递质 GABA 以及主要兴奋性神经递质 Glu 和 Gln，以及快速且成熟的质子回波平面光谱成像 (PEPSI) 方法。这项新技术将专门的 MEGAPRESS GABA 采集与 J 解析的 Glu/Gln 采集交织在一起，在一小时内生成这些代谢物在大脑中的实际代谢图像。交叉使用这两种方法的优点是可以在同一时间过程中同时获取 GABA、Glu 和 Gln，这是在急性药物挑战后跟踪该神经递质系统活动所必需的重要方面。我们将首先进行一系列模型实验来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、精确地跟踪不同浓度的 GABA、Glu 和 Gln 的能力。然后，我们将在健康志愿者样本中评估我们的新技术在体内的表现，以评估我们在活体大脑中代谢物测量的准确性和精确度。在我们的最终实验中，我们将对健康志愿者进行药物挑战，以评估我们的方法在检测和量化药物引起的大脑神经递质变化方面的临床效用。该项目完成后，我们将开发出一种重要的 GABA、Glu 和 Gln 体内成像工具。从公共卫生的角度来看，该工具将使我们能够绘制出这些化合物在大脑回路中的不同水平，从而进一步了解人脑中神经递质系统的工作原理。这将对精神病学和成瘾领域的研究产生重要影响，以了解成瘾性疾病中存在的神经化学畸变。 公共健康相关性：该项目的目标是在我们的 4 Tesla 全身研究扫描仪上开发磁共振波谱协议，该协议将差异编辑的卓越 GABA 编辑特性与回波平面波谱成像的快速多体素覆盖相结合。该技术将允许快速而准确地确定人脑中的全局 GABA 分布，这可能作为药理学研究的工具，调查 GABA 能药物在多个时间点的分布和摄取/清除。