Novel MRS Neurotechnology for Imaging GABA & Glutamate Function in Schizophrenia

描述(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对正常的大脑功能至关重要。由于谷氨酸和/或GABA能神经递质的调节失调与多种神经和神经精神疾病有关，通过体内研究这些神经递质系统的功能，可以在更好地理解这些疾病的病理生理学方面取得重大进展。然而，目前缺乏有效的体内检测GABA和Glu的方法。在这份神经技术研究、开发和增强拨款申请中，申请者提议开发一种新的非侵入性质子磁共振波谱(1HMRS)技术，该技术将能够在体内对人脑中的GABA和Glu进行强有力的检测和功能研究。具体地说，这项研究的目标是：(A)开发和验证一系列新颖的体积选择性、“单次激发”选择性同核多量子相干(sh-MQC)转移技术，用于在人脑中有效和明确地单独检测GABA或Glu，或同时检测这两种化合物；(B)通过在体内实施相控阵多通道接收器线圈和同核单频去耦合技术来提高灵敏度和检测简易性，这将最大限度地减少光谱重叠并提高光谱纯度；(C)透过进行重测信度量度及计算变异系数，以评估所开发技术的可靠性；及。(D)进行一项先导临床研究研究，以量度及比较精神分裂症患者及健康受试者前额叶皮质谷氨酸及氨基丁酸的基线水平。如果开发成功，建议的GABA和Glu检测技术将具有非常重要的意义，因为1H MRS是目前唯一一种能够在体内直接测量这两种氨基酸神经递质的非侵入性技术。因此，虽然这项研究将强调拟议技术在精神分裂症研究中的效用，但应该强调的是，这将是一项广泛适用的技术，将在任何GABA和/或Glu功能失调的大脑疾病(例如癫痫、药物滥用、焦虑障碍、严重抑郁症)的研究中使用。

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.