Edited Magnetic Resonance Spectroscopy of the Pediatric Brain

总结 人类神经化学在幼儿期经历了戏剧性的变化，由于快速的节奏， 发展然而，通过磁共振非侵入性地评估神经化学的技术 MRS（磁共振波谱）在幼儿中的应用有限。光谱编辑是检测MRS的金标准 来自关键神经代谢物的信号，如神经递质谷氨酸（Glu）和GABA， 神经调节剂N-乙酰基谷氨酸（NAAG）和天冬氨酸（Asp），氧化还原化合物谷胱甘肽 (GSH)和抗坏血酸（Asc）、厌氧糖酵解产物乳酸（Lac）和膜脂质前体 磷酸乙醇胺（PE）。测量这些低浓度代谢物对于研究 健康和中断的神经发育，包括抑制功能障碍，氧化应激，髓鞘形成和 线粒体代谢紊乱 到目前为止，光谱编辑尚未广泛应用于儿科-可以说，他们将在竞技场 最有力地利用科学发现和临床价值。该项目将开发收购 和分析工具，用于儿科大脑中的多代谢物MRS，专注于开发运动鲁棒性 收购。它还将获得儿科光谱最佳实践分析的参考数据，包括 大分子背景光谱和代谢物弛豫测定法。 该项目将与健康大脑和儿童发展（六溴环十二烷）进行关键的推拉互动 研究，一项25个地点的神经发育危险因素的国家研究（包括四个地点，在这个 建议）。六溴环十二烷采用PI Edden小组开发的采集和分析方法 （HERCULES和Osprey），Edden和Wisnowski博士是六溴环十二烷MRS的共同主席， 组该项目方法的传播将直接支持六溴环十二烷， 儿科队列的方法开发将使我们能够直接解决技术问题， 在HBCD中出现。在六溴环十二烷研究期间获得的数据将补充本赠款中获得的数据， 对儿童早期的神经代谢轨迹有了深刻的新认识。

Summary Human neurochemistry undergoes dramatic changes in early childhood, due to the rapid pace of development. However, techniques for assessing neurochemistry non-invasively by magnetic resonance spectroscopy (MRS) in young children are limited. Spectral editing is the gold-standard for detecting MRS signals from key neurometabolites such as the neurotransmitters glutamate (Glu) and GABA, the neuromodulators N-acetyl aspartyl glutamate (NAAG) and aspartate (Asp), the redox compounds glutathione (GSH) and ascorbate (Asc), the anaerobic glycolysis product lactate (Lac), and the membrane lipid precursor phosphorylethanolamine (PE). Measurement of these lower-concentration metabolites is vital for investigating healthy and disrupted neurodevelopment, including inhibitory dysfunction, oxidative stress, myelination and mitochondrial metabolic disruption. To date, spectral editing has not been applied at large in pediatrics – arguably the arena in which they will be leveraged most powerfully for scientific discovery and clinical value. This project will develop acquisition and analysis tools for multi-metabolite MRS in the pediatric brain, focusing on developing motion-robust acquisitions. It will also acquire reference data for the best-practice analysis of pediatric spectra, including the macromolecular background spectrum and metabolite relaxometry. This project will have a key push-pull interaction with the HEALthy Brain & Child Development (HBCD) Study, a 25-site national study of neurodevelopmental risk factors (including four sites in this proposal). HBCD applies the acquisition and analysis methods developed by PI Edden's group (HERCULES and Osprey), and Drs. Edden and Wisnowski are co-chairs of the HBCD MRS working group. Dissemination of methods from this project will directly support HBCD, and this new focus on methods development for pediatric cohorts will allow us to directly address technical issues as they arise in HBCD. Data acquired during HBCD will supplement the data acquired in this grant as we develop a profound new understanding of the neurometabolic trajectory of early childhood.