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的脑功能至关重要。由于谷氨酸能和/或gaba能神经传递的失调与多种神经和神经精神疾病有关，因此通过对这些神经递质系统功能的体内研究，可以更好地了解这些疾病的病理生理学。然而，目前缺乏有效的体内GABA和Glu检测方法。在这项神经技术研究、开发和增强拨款申请中，申请人提议开发一种新型的无创质子磁共振波谱（1H MRS）技术，该技术将能够在人脑中进行GABA和Glu的体内检测和功能研究。具体来说，本研究的目标是(a)开发和验证一系列新型的体积选择性，“单次”选择性同核多量子相干（sh-MQC）转移技术，用于在人脑中有效且明确地检测GABA或Glu，或同时检测这两种化合物；(b)利用相控阵多通道接收线圈和同核单频解耦技术在体内实现所开发的序列，以减少光谱重叠和提高光谱纯度，从而提高灵敏度和检测便性；(c)通过进行重测信度测量和计算变异系数来估计所开发技术的信度；(d)开展一项试点临床研究，在这项研究中，新技术将被用于测量和比较精神分裂症患者和健康受试者前额皮质谷氨酸和氨基丁酸的基线水平。如果开发成功，所提出的GABA和Glu检测技术将具有重要意义，因为1H MRS是目前唯一可以直接测量体内这两种氨基酸神经递质的无创技术。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，这将是一项广泛适用的技术，将在GABA和/或Glu功能可能失调的任何脑部疾病（例如癫痫、药物滥用、焦虑症、重度抑郁症）的研究中得到应用。

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.