Robust 1H MRSI of GABA, Glutamate, Glutamine, and Glutathione

项目摘要 了解神经递质的活性是阐明正常和病变神经元的基础 功能，谷氨酸(Glu)和氨基丁酸(γ)是大脑的主要兴奋性和 抑制性神经递质。这样的理解在自闭症谱系障碍(ASD)中尤为关键， 神经发育障碍的特征是持续的社交沟通障碍和受限， 重复的、刻板的行为模式。尽管ASD的表现和严重程度各不相同，但它发生在 所有族裔和社会经济群体，具有终生影响，据估计，#年每68名儿童中就有1名受到影响。 美国。不幸的是，这些疾病的病因还没有完全了解，而且这项技术 开发研究ASD脑神经化学的新型非侵入性成像工具的发展建议 《生物标记物》是对美国国立卫生研究院PA 10-158《自闭症谱系障碍研究》的回应。创新将是 在该项目下进行的评估将不仅有助于研究ASD，还将有助于其他神经精神病学和 神经发育障碍，需要先进的成像技术。 尽管ASD具有异质性，但患者可能共享最终共同的生化途径，并有可能 对类似的治疗有反应，现在推测ASD是由于 兴奋性和抑制性神经递质。被称为“E/I平衡”的理论，这两种动物的发现 模型和人类提示ASD的特征是关键大脑区域的过度兴奋，这是由于 Glu升高和/或GABA降低。而在体内，这种神经化学失衡的证据正在开始 通过使用J-编辑的1H磁共振波谱(兆兆出版社是当前的 选择的方法)健壮的活体测量既耗时又有问题。GLU测量为 很简单，但很难从密切相关的谷氨酰胺(Gln)中分离出来。此外，共同编辑 大分子(MMS)与目标GABA信号重叠并且占检测信号的40%-60%， 导致研究人员将结果数据称为GABA+MMS或简称为GABA+。MRS检测到的彩信是 也有报道显示出地区差异，正常受试者的可变性，以及对两个年龄的依赖 和病理学。即使对于单体素研究，先前提出的MM抑制技术也没有被广泛使用， 要么耗时，要么对B0磁场变化高度敏感。 该提案试图通过系统的设计、实现和测试来克服这些限制 用于测量稳健的MM抑制J编辑的单体素(AIMS 1和2)和多体素(AIM 3)序列 这些有针对性的神经化学物质，可以从多个大脑区域进行省时的测量。这些新的 将使用工具评估被诊断为自闭症的青少年患者的神经化学失衡(目标4)。

Project Abstract Understanding neurotransmitter activity is fundamental to elucidating normal and diseased neuronal function, with glutamate (Glu) and γ-aminobutyric acid (GABA) being the brain's primary excitatory and inhibitory neurotransmitters. Such understanding is particularly critical in autism spectrum disorder (ASD), a set of neurodevelopment disorders characterized by persistent deficits in social communication and restricted, repetitive, and stereotyped patterns of behavior. Although varying in presentation and severity, ASD occurs in all ethnic and socioeconomic groups, has a lifelong duration, and affects an estimated 1 out of 68 children in the United States. Unfortunately, the etiologies of these disorders are not fully understood, and this technical development proposal to develop novel non-invasive imaging tools for studying ASD brain neurochemical biomarkers is in response to NIH PA 10-158 “Research on Autism Spectrum Disorders”. The innovations to be evaluated under this project will help not only investigating ASD, but also other neuropsychiatric and neurodevelopmental disorders where advanced imaging techniques are needed. Despite the heterogeneity of ASD, patients may share final common biochemical pathways and potentially be responsive to similar treatments, and ASD is now hypothesized to result from an imbalance between excitatory and inhibitory neurotransmitters. Known as the “E/I balance” theory, findings from both animal models and humans suggest ASD is characterized by hyper-excitability in critical brain regions due to increased Glu and/or decreased GABA. While in vivo evidence of such neurochemical imbalances is beginning to emerge through the use of J-edited 1H magnetic resonance spectroscopy (MEGA-PRESS being the current method of choice) robust in vivo measurements are time-consuming and problematic. Glu measurement is straightforward, but separation from closely related glutamine (Gln) is difficult. Furthermore, co-edited macromolecules (MMs) overlap the targeted GABA signal and account for 40-60% of the detected signal, leading investigators to refer to the resulting data as GABA+MMs or simply GABA+. MRS-detected MMs are also reported to exhibit regional variations, variability across normal subjects, and dependence on both age and pathology. Even for single-voxel studies, prior proposed MM-suppression techniques are not widely used, being either time-consuming or highly sensitive to B0 magnetic field variations. This proposal seeks to overcome these limitations via the systematic design, implementation, and testing of robust MM-suppressed J-edited single-voxel (Aims 1 and 2) and multi-voxel (Aim 3) sequences to measure these targeted neurochemicals, yielding time-efficient measurements from multiple brain regions. These new tools will be used to assess neurochemical imbalances in adolescent patients diagnosed with ASD (Aim 4).