Understanding the long term impact of COVID-19 on the brain through advanced MR imaging and spectroscopy

项目摘要/摘要 自世界卫生组织于2020年3月宣布新冠肺炎为大流行以来，越来越多的人 有证据表明，这种疾病影响到多个器官，包括中枢神经系统(CNS)。 新冠肺炎对急性期中枢神经系统影响的临床、磁共振研究 影像(MRI)和波谱(MRS)，通过血浆生物标记物和尸检，有神经症状 在1/3至2/3的住院重症病例中出现。在急性期之后，大约10%的患者 经历长期疾病，在此期间出现神经症状(头痛、认知障碍和疲劳) 是新冠肺炎幸存者报告的前十大症状之一。这些长期存在的潜在生物学现象 症状未知；因此，系统研究这种疾病的病理生理学的前瞻性研究 人们迫切需要后遗症。 根据新冠肺炎的临床表现，近几个月来有关冠状病毒相关症状的报告 感染后，包括帕金森综合症和其他延迟的神经和神经认知的报告 并发症从轻微到严重，以及已知的脑部病理的外周触发因素， 神经炎(Aim 1)、神经变性(Aim 2)和脑血管疾病(Aim 3) 有望成为CNS长期病理生理学的重要组成部分。 COVID大脑高级成像网络(COVID-Brain)是由六个人组成的联盟 系统和前瞻性阐明新冠肺炎中枢神经系统长期病理生理机制的机构 在3特斯拉使用高度灵敏、协调、先进的MRI/MRS技术，并采用标准化 神经学和神经心理学评估和炎性血液生物标记物。目前有五个网站 其他多站点神经成像计划的合作伙伴(明尼苏达大学、罗切斯特梅奥诊所、哈佛大学 大学/马萨诸塞州综合医院、约翰霍普金斯大学、休斯顿卫理公会研究院) 将收集纵向多模式MRI(T1、FLAIR、弥散磁共振、磁化率加权MRI、单模式和 多体素MRS和伪连续动脉自旋标记)、临床、神经认知和血液生物标记物 来自实验室确诊的有神经系统症状的冠状病毒感染后病例(N=200)和匹配的对照组的数据 100例。南加州大学的神经成像实验室(LONI)将作为 数据管理站点。磁共振标记的组间差异和随时间的变化 神经炎症、神经变性、缺氧/缺血和心血管疾病及其与特异性肿瘤的关系 将对神经症状、认知功能和炎性血液生物标记物进行调查。 这项研究提供的机械性见解将为患者的护理和治疗提供信息 预计在未来几年将遭受大流行的长期后果。

PROJECT SUMMARY/ABSTRACT Since the World Health Organization declared COVID-19 a pandemic in March 2020, increasing evidence has shown that the disease affects multiple organs, including the central nervous system (CNS). Effects of COVID-19 on the CNS in the acute phase were documented clinically, by magnetic resonance imaging (MRI) and spectroscopy (MRS), by plasma biomarkers and at autopsy, with neurological symptoms manifesting in 1/3 to 2/3 of hospitalized, severe cases. After the acute phase, approximately 10% of patients experience prolonged illness, during which neurological symptoms (headaches, cognitive blunting, and fatigue) are among the top 10 symptoms reported by COVID-19 survivors. The underlying biology of these prolonged symptoms is unknown; therefore, prospective studies to systematically investigate the pathophysiology of such sequelae are urgently needed. Based on the clinical presentation of COVID-19, reports of COVID-related symptoms in the months following the infection, including reports of Parkinsonism and other delayed neurological and neurocognitive complications ranging from mild-to-severe, and known peripheral triggers of cerebral pathology, neuroinflammation (Aim 1), neurodegeneration (Aim 2) and cerebrovascular disease (CVD) (Aim 3) are expected to be important components of long-term CNS pathophysiology. The COVID BRain Advanced Imaging Network (COVID-BRAIN) was formed as a Consortium of six institutions to systematically and prospectively elucidate the long-term CNS pathophysiology of COVID-19 using highly sensitive, harmonized, advanced MRI/MRS technology at 3 tesla in conjunction with standardized neurological and neuropsychological evaluation and inflammatory blood biomarkers. Five sites that currently partner in other multi-site neuroimaging initiatives (University of Minnesota, Mayo Clinic Rochester, Harvard University/Massachusetts General Hospital, Johns Hopkins University, Houston Methodist Research Institute) will collect longitudinal multi-modal MRI (T1, FLAIR, diffusion MRI, susceptibility-weighted MRI, single- and multi-voxel MRS and pseudo-continuous arterial spin labeling), clinical, neurocognitive and blood biomarker data from laboratory confirmed post-COVID cases with neurological symptoms (N=200) and matched controls (N=100). The Laboratory of Neuro Imaging (LONI) at the University of Southern California will serve as the data management site. Group differences and change over time in MR markers indicative of neuroinflammation, neurodegeneration, hypoxia/ischemia and CVD and their associations with specific neurological symptoms, cognitive function, and inflammatory blood biomarkers will be investigated. The mechanistic insights provided by this study will inform the care and treatment of patients that are expected to suffer long-term consequences of the pandemic for the years to come.