Novel MRS Neurotechnology for Imaging GABA & Glutamate Function in Schizophrenia

描述（由申请人提供）：谷氨酸（Glu）和GABA的兴奋性和抑制性氨基酸神经递质系统分别对正常脑功能至关重要。由于多巴胺能和/或GABA能神经传递的失调与多种神经系统和神经精神疾病有关，通过对这些神经递质系统功能的体内研究，可以更好地理解这些疾病的病理生理学。然而，目前缺乏用于体内GABA和Glu检测的有效方法。在这项神经技术研究、开发和增强资助申请中，申请人提议开发一种新型的非侵入性质子磁共振波谱（1H MRS）技术，该技术将能够对人脑中的GABA和Glu进行稳健的体内检测和功能研究。具体地说，本研究的目的是（a）开发和验证一系列新的体积选择性“单次”选择性同源多量子相干（sh-MQC）转移技术，用于在人脑中有效和明确地检测GABA或Glu单独或同时检测两种化合物;（B）通过用相控阵多通道接收器线圈和体内同相单频去耦技术实施所开发的序列来增强灵敏度和检测容易性，这将使光谱重叠最小化并增加光谱纯度;（c）通过进行重复测试的可靠性测量并计算变异系数来估计所开发技术的可靠性;及（d）进行一项试验性临床研究，采用新技术量度和比较精神分裂症患者和健康受试者的前额叶皮质Glu和GABA的基线水平。如果成功开发，所提出的GABA和Glu检测技术将是非常重要的，因为1H MRS是目前唯一的非侵入性技术，提供了直接测量这两种氨基酸神经递质在体内的可能性。因此，虽然这项研究将强调所提出的技术在精神分裂症研究中的实用性，但应该强调的是，这将是一种广泛适用的技术，可用于任何脑部疾病的研究（例如，癫痫、物质滥用、焦虑症、重性抑郁症），其中GABA和/或Glu功能可能失调。

DESCRIPTION (provided by applicant): The excitatory and inhibitory amino acid neurotransmitter systems of glutamate (Glu) and GABA, respectively, are critical for normal brain function. As dysregulation of glutamatergic and/or GABAergic neurotransmission has been implicated in a variety of neurological and neuropsychiatric disorders, significant advances toward a better understanding of the pathophysiology of such disorders can be achieved through in vivo investigations of the function of these neurotransmitter systems. However, there is currently a paucity of effective methods for in vivo GABA and Glu detection. In this Neurotechnology Research, Development and Enhancement grant request the applicants propose to develop a novel noninvasive proton magnetic resonance spectroscopy (1H MRS) technology that would enable robust in vivo detection and functional studies of GABA and Glu in human brain. Specifically, this research will aim (a) to develop and validate of a family of novel volume-selective, "single-shot" selective homonuclear multiple quantum coherence (sh-MQC) transfer techniques for the efficient and unambiguous detection of either GABA or Glu alone, or of the two compounds simultaneously, in vivo in human brain; (b) to enhance sensitivity and detection ease by implementing the developed sequences with a phased-array multichannel receiver coil, and homonuclear single-frequency decoupling techniques in vivo, which would minimize spectral overlap and increase spectral purity; (c) to estimate the reliability of the developed technology by performing test-retest reliability measurements and computing the coefficient of variation ; and (d) to conduct a pilot clinical research study in which the new technology would be implemented to measure and compare baseline levels of prefrontal cortical Glu and GABA in schizophrenics and in healthy subjects. If successfully developed, the proposed GABA and Glu detection technology would be highly significant in that 1H MRS is currently the only noninvasive technique that offers the possibility to directly measure these two amino acid neurotransmitters in vivo. Thus, while this research will emphasize the utility of the proposed technology in the study of schizophrenia, it should be stressed that this will be a widely applicable technology that will find use in the study of any brain disorder (e.g.,epilepsy, substance abuse, anxiety disorder, major depression disorder) in which GABA and/or Glu function may be dysregulated.