MULTIPLE QUANTUM CHEMICAL SHIFT IMAGING OF GABA IN BRAIN

γ -氨基丁酸（GABA）是人类皮层中主要的抑制性神经递质。在我们的实验室中，我们开发了单体素1H磁共振波谱（MRS）编辑方法，用于测量人脑中的GABA浓度。使用GABA MRS的研究为GABA增强抗癫痫药物的机制和GABA代谢在成人和青少年癫痫以及最近的酒精中毒和抑郁症中的改变提供了重要的见解。这些发现支持GABA代谢在神经和精神疾病的发病机制和治疗中的重要作用。GABA光谱成像技术（SI）的发展将极大地增强MRS研究的可用信息。然而，仍然存在重大挑战，包括1)消除与强烈肌酸共振的重叠，2)从共编辑大分子的共振中分离GABA共振，3)开发反向检测方法，允许用1H MRS灵敏度测量注入13C同位素的GABA合成，4)实现尽可能高的灵敏度和分辨率。最近，我们利用一种新的多量子（MQ）滤波方法在人脑中获得了第一个GABA SI，该方法可以完全抑制重叠肌酸，而不牺牲相对于J编辑方法的灵敏度。在本提案中，我们将扩展这些结果，通过开发体内多量子二维MRS方法，从污染的大分子共振中获得GABA的明确分离。将开发逆单量子二维方法，用于绘制灌注[1- 13C]葡萄糖中[2-13C] GABA的周转率。与布鲁克海文国家实验室的H.P. Hetherington博士合作，这些方法将与4T的高分辨率，高场SI相结合。这些方法将在适当的幻影，动物模型和人类志愿者中进行测试和验证。IT和4T。本提案的总体目标是将GABA浓度和合成速率的SI发展成为临床研究GABA代谢在正常脑功能和疾病中的作用的可靠方法。

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in human cortex. In our laboratory we have developed single-voxel 1H magnetic resonance spectroscopy (MRS) editing methods for measuring GABA concentration in the human brain. Studies using GABA MRS have provided important insight into the mechanism of GABA-enhancing antiepileptic drugs and altered-GABA metabolism in disease including adult and juvenile epilepsy and recently alcoholism and depression. These findings support an important role of GABA metabolism in the pathogenesis and treatment of neurological and psychiatric disorders. The development GABA spectroscopic imaging (SI) for mapping regional GABA concentrations and synthesis rates will greatly enhance the information available from MRS studies. However significant challenges remain including 1) elimination of overlap with the intense creatine resonance, 2) separation of the GABA resonance from the resonance of co-edited macromolecules 3) the development of inverse detection methods which allow measurement of GABA synthesis from infused 13C isotope with 1H MRS sensitivity, 4) achievement of the highest possible sensitivity and resolution. Recently we have obtained the first GABA SI in human brain by the use of a novel multiple quantum (MQ) filtering method which provides complete suppression of overlapping creatine without sacrificing sensitivity relative to J editing methods. In this proposal we will extend these results to obtain unequivocal separation of GABA from contaminating macromolecule resonances through the development of in vivo multiple quantum 2D MRS methods. Inverse single quantum 2D methods will be developed for mapping of the turnover rate of [2-13C] GABA from infused [1- 13C]glucose. In collaboration with Dr. H.P. Hetherington at Brookhaven National Laboratories these methods will be combined with high resolution, high field SI at 4T. These methods will be tested and validated in appropriate phantoms, animal models, and human volunteers at 2.IT and 4T. The overall goal of this proposal is to develop SI of GABA concentration and synthesis rate into a robust method for clinical research into the role of GABA metabolism in normal brain function and in disease.