Edited Magnetic Resonance Spectroscopy of the Pediatric Brain

摘要 人类神经化学在儿童早期经历了戏剧性的变化，这是由于 发展。然而，通过磁共振非侵入性评估神经化学的技术 幼儿的波谱(MRS)是有限的。光谱编辑是检测MRS的金标准 来自关键神经代谢产物的信号，如神经递质谷氨酸(Glu)和GABA， 神经调节剂N-乙酰天冬氨酸(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)，以及膜脂前体 磷酰乙醇胺(PE)。对这些低浓度代谢物的测量对于研究是至关重要的 健康和紊乱的神经发育，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，光谱编辑还没有广泛应用于儿科--可以说是他们将在其中的竞技场 在科学发现和临床价值方面发挥最大的杠杆作用。该项目将开发收购 和儿科大脑多代谢物MRS的分析工具，专注于发展运动健壮 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计量学。 该项目将与健康大脑和儿童发展(HBCD)进行关键的推拉互动 研究，一项关于神经发育风险因素的25个地点的全国性研究(包括本研究中的四个地点 提案)。HBCD采用了皮埃登小组开发的采集和分析方法 (Hercules和Osprey)，Edden博士和Wisnowski博士是HBCD夫人Working的联合主席 一群人。该项目方法的传播将直接支持HBCD，这一新的重点是 儿科队列的方法开发将使我们能够直接解决技术问题，因为它们 在HBCD兴起。在HBCD期间获得的数据将补充在本赠款中获得的数据，因为我们 对儿童早期的神经代谢轨迹有深刻的新认识。

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.