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: 8009607
• 负责人: JOHN E JENSEN
• 金额: $ 16.7万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8009607
• 关键词: Acute; Address; Arts; Blinded; Brain; Brain region; Clinical; Cocaine; Cohort Studies; Collection; Data; Detection; Equilibrium; Functional disorder; Glutamates; Glutamine; Goals; Gray unit of radiation dose; 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; 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光谱成像（MRSI）序列，该序列将允许在临床合理的扫描时间（小于1小时）内最佳采集GABA、谷氨酸（Glu）和谷氨酰胺（Gln）光谱。我们提出的方法将结合联合收割机目前，国家的最先进的磁共振波谱（MRS）技术在体内测量的主要抑制性神经递质GABA，以及主要兴奋性神经递质，谷氨酸和谷氨酰胺与快速和建立的质子回波平面光谱成像（PEPSI）的方法。这项新技术将专门的MEGAPRESS GABA采集与J-分辨Glu/Gln采集交错，以在一小时内产生这些代谢物在大脑中的实际代谢图像。交错这两种方法的优点是在相同的时间过程中同时采集GABA、Glu和Gln，这是在急性药物激发后跟踪该神经递质系统的活性所必需的重要方面。我们将首先进行一系列的幻影实验，以评估我们的序列在体外的性能，并验证我们的方法，评估我们的技术的能力，准确和精确地跟踪不同浓度的GABA，Glu和Gln的重复测量。然后，我们将评估我们的新技术在健康志愿者样本中的体内性能，以评估我们在活体大脑中代谢物测量的准确性和精确度。在我们的最后一个实验中，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诱导的大脑神经递质变化方面的临床实用性。在这个项目完成后，我们将开发一个重要的工具，在体内成像的GABA，Glu和Gln。从公共卫生的角度来看，这个工具将使我们能够进一步了解这种神经递质系统在人类大脑中的工作方式，让我们能够绘制出这些化合物在大脑回路中的各种水平。这将在精神病学研究和成瘾领域产生重要影响，以了解成瘾性疾病中存在的神经化学畸变。 公共卫生相关性：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磁共振光谱协议，该协议将差异编辑的上级GABA编辑特性与回波平面光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整体GABA分布，这可能作为药理学研究的工具，研究GABA能药物在几个时间点的分布和摄取/洗脱。