Ultra-high field GluCEST MRI and MRS in youth at risk for psychosis

摘要：精神病通常发生在青春期或成年早期。故障 神经递质系统如谷氨酸盐与精神病的疾病进展有关。变化 精神病患者大脑中谷氨酸可能有几个来源，因此，许多一线抗精神病药物 间接靶向谷氨酸系统并减轻临床症状。不幸的是， 脑内谷氨酸系统的改变在空间上受到传统磁共振的限制 技术.但是，最近一种新的7 T MRI技术（GluCEST）表明，大脑谷氨酸水平是 在精神病谱系的青年和精神分裂症患者中， 典型的发育中的青年。在这里，我们建议扩展这项新的工作，直接测量谷氨酸内的 有患精神病风险的病人的大脑。因此，这项建议的动机是需要更好地 了解大脑神经化学，结构和功能在正常发育和 精神病早期在这项研究中，我们试图1）比较不同年龄段的儿童的发育指标， 在一组典型发育（TD）青年中，那些处于精神病临床高风险（Psychosis）的人， 坦率的精神病（PSY）个体; 2）将大脑谷氨酸盐的变化与年龄和诊断联系起来- 相关结构网络的变化，在那些有风险发展为精神病;和3）建立比较 7 T MRI（1HMRS vs. GluCEST）的谷氨酸测量数据。我们将招募并跟踪35名TD，PSB和PSY 在五年的融资期内。成像数据将在7 T下采集，分析将利用最新进展 在网络科学和机器学习方面。我们相信这种创新的方法可以大大提高我们的 了解精神病中谷氨酸功能减退的病因，并提供精确的进展 精神病学中的医学通过多层次的分析，本创新性研究将提供一个 我们对精神病的神经发育基础的理解有了实质性的进展。

ABSTRACT: Psychosis commonly develops in adolescence or early adulthood. Malfunctioning neurotransmitter systems, such as glutamate, are implicated in the disease progression of psychosis. Changes in brain glutamate in psychosis likely have several sources, as such, many frontline antipsychotic medications indirectly target the glutamate system and alleviate clinical symptoms. Unfortunately, monitoring in vivo alterations of the glutamate system within the brain are spatially limited by traditional magnetic resonance techniques. But, recently a novel 7T MRI technique (GluCEST) has shown that brain glutamate levels are lower across the brain in youth on the psychosis spectrum and patients with schizophrenia as compared to typically developing youth. Here, we propose to extend this novel work to directly measure glutamate within the brain of patients at risk for developing psychosis. Thus, this proposal is motivated by the need to better understand associations of brain neurochemistry, structure and function in both normal development and during early psychosis. In this study, we seek to 1) compare measures of glutamatergic development across the cortex in a cohort of typically developing (TD) youth, those at-clinical high-risk for psychosis (CHR) and individuals with frank psychosis (PSY); 2) associate changes in brain glutamate with age- and diagnosis- related structural network changes in those at risk for developing psychosis; and 3) to establish comparison data of glutamate measures at 7T MRI (1HMRS vs. GluCEST). We will recruit and follow 35 TD, CHR and PSY over the 5-year funding period. Imaging data will be acquired at 7T and analyses will leverage recent advances in network science and machine learning. We believe this innovative approach can significantly advance our understanding of the etiology of glutamate hypofunction in psychosis and provide advances to precision medicine in psychiatry. Through the proposed multi-level analysis, this innovative research will provide a substantial advance in our understanding of the neurodevelopmental substrates of psychosis.