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

项目总结/摘要 自世界卫生组织于二零二零年三月宣布COVID-19为大流行以来， 有证据表明，该疾病影响多个器官，包括中枢神经系统（CNS）。 通过磁共振临床记录了COVID-19对急性期CNS的影响 通过血浆生物标志物和尸检进行影像学（MRI）和波谱（MRS）检查，并伴有神经系统症状 出现在1/3到2/3的住院重症病例中。在急性期之后，大约10%的患者 经历长期的疾病，在此期间，神经系统症状（头痛，认知迟钝和疲劳） 是COVID-19幸存者报告的十大症状之一。这些长期存在的潜在生物学 症状是未知的;因此，前瞻性研究，系统地调查这种疾病的病理生理学， 后遗症是迫切需要的。 根据COVID-19的临床表现， 感染后，包括帕金森综合征和其他迟发性神经和神经认知障碍的报告 轻度到重度的并发症，以及已知的脑病理学外周触发因素， 神经炎症（Aim 1）、神经变性（Aim 2）和脑血管疾病（CVD）（Aim 3）是 预期是长期CNS病理生理学的重要组成部分。 COVID BRAIN高级成像网络（COVID-BRAIN）由六个成员组成 机构系统和前瞻性地阐明COVID-19的长期CNS病理生理学 使用高灵敏度、协调、先进的3特斯拉MRI/MRS技术， 神经学和神经心理学评估以及炎症血液生物标志物。五个网站目前 其他多站点神经成像计划的合作伙伴（明尼苏达大学、马约诊所、罗切斯特、哈佛 大学/马萨诸塞州总医院、约翰霍普金斯大学、休斯顿卫理公会研究所） 将收集纵向多模态MRI（T1、FLAIR、弥散MRI、磁共振加权MRI、单模态和 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志物 来自实验室确诊的COVID后有神经系统症状的病例（N=200）和匹配对照的数据 （N=100）。南加州大学的神经成像实验室（LONI）将作为 数据管理网站。组间差异和MR标志物随时间的变化表明 神经炎症、神经变性、缺氧/缺血和CVD以及它们与特异性 将研究神经系统症状、认知功能和炎性血液生物标志物。 这项研究提供的机制见解将告知患者的护理和治疗， 预计在未来几年将受到大流行病的长期影响。

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.