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

通过先进的 MR 成像和光谱学了解 COVID-19 对大脑的长期影响

• 批准号: 10445068
• 负责人: KEJAL KANTARCI
• 金额: $ 64.42万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10445068
• 关键词: Acute; Affect; Aging; Anisotropy; Antibodies; Atrophic; Autopsy; Basal Ganglia; Biochemical; Biological; Biological Markers; Biology; Biomedical Engineering; Blood; Blood Vessels; Brain; Brain Hypoxia-Ischemia; COVID-19; COVID-19 impact; COVID-19 survivors; California; Caring; Central Nervous System Infections; Cerebellum; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Choline; Clinic; Clinical; Cognitive; Cognitive deficits; Consensus; Data; Demyelinations; Deposition; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Enrollment; Evaluation; Fatigue; Functional disorder; Funding; General Hospitals; Glutamates; Glutamine; Goals; Guidelines; Headache; Hemorrhage; Hypoxia; Image; Imaging technology; Individual; Infarction; Infection; Inflammatory; Injury; Inositol; Institution; Interleukin-1; Interleukin-6; Investigation; Iron; Laboratories; Lesion; Leukoencephalopathy; Long-Term Effects; Lung; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Massachusetts; Measures; Metabolic Diseases; Methodist Church; Methodology; Minnesota; N-acetylaspartate; Nerve Degeneration; Neuraxis; Neurocognitive; Neurodegenerative Disorders; Neurologic; Neurologic Examination; Neurologic Symptoms; Neuropsychology; Organ; Parkinsonian Disorders; Participant; Pathologic; Pathology; Patients; Perfusion; Perfusion Weighted MRI; Peripheral; Phase; Plasma; Predisposition; Prospective Studies; Reporting; Research; Research Institute; Respiration Disorders; Respiratory Signs and Symptoms; SARS-CoV-2 infection; Site; Spectrum Analysis; Standardization; Symptoms; TNF gene; Technology; Time; Underrepresented Minority; Universities; Vaccines; Vendor; White Matter Hyperintensity; World Health Organization; arterial spin labeling; astrogliosis; base; cerebrovascular; clinical trial readiness; cognitive function; coronavirus disease; data management; experience; high risk; imaging biomarker; inflammatory marker; insight; long term consequences of COVID-19; multimodality; neuroimaging; neuroinflammation; neurologic sequelae of COVID-19; neuron loss; neuropsychiatry; pandemic disease; persistent symptom; post-COVID-19; prospective; quantitative imaging; spectroscopic imaging; systemic inflammatory response; therapy development

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.

项目摘要/摘要 自从世界卫生组织在2020年3月宣布Covid-19的大流行以来， 证据表明该疾病会影响多个器官，包括中枢神经系统（CNS）。 COVID-19对急性期CNS的影响通过磁共振在临床上记录在临床上 成像（MRI）和光谱法（MRS），血浆生物标志物和尸检时具有神经系统症状 在1/3至2/3的住院严重病例中表现出来。急性阶段之后，约有10％的患者 经历长期疾病，在此期间神经系统症状（头痛，认知钝和疲劳） 是Covid-19幸存者报告的十大症状之一。这些延长的基本生物学 症状未知；因此，前瞻性研究以系统地研究这种病理生理学 迫切需要后遗症。 基于COVID-19的临床表现，在几个月中有关相关症状的报道 感染后，包括帕金森氏症的报道以及其他延迟的神经认知和神经认知的报道 从轻度到重度和已知的脑病理周围触发因素等并发症， 神经炎症（AIM 1），神经变性（AIM 2）和脑血管疾病（CVD）（AIM 3）为 预计将是长期CNS病理生理学的重要组成部分。 Covid Brain Advanced Imaging网络（Covid-Brain）成立为六个财团 制度系统地阐明了COVID-19的长期CNS病理生理学 使用标准化的高度敏感，统一的，高级的MRI/MRS技术与标准化 神经和神经心理学评估以及炎症性血液生物标志物。目前五个网站 其他多站点神经影像倡议的合作伙伴（明尼苏达大学，梅奥诊所罗切斯特，哈佛大学 休斯顿卫理公会研究所约翰·霍普金斯大学大学/马萨诸塞州大学综合医院） 将收集纵向多模式MRI（T1，Flair，扩散MRI，敏感性加权MRI，单和 多素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 来自实验室的数据确认有神经系统症状（n = 200）和匹配对照的病后病例 （n = 100）。南加州大学的Neuro Imaging（LONI）实验室将担任 数据管理网站。小组差异和随着时间的变化在MR标记中表示 神经炎症，神经变性，缺氧/缺血和CVD及其与特定的关联 将研究神经系统症状，认知功能和炎性血液生物标志物。 这项研究提供的机械见解将为患者的护理和治疗提供信息 预计将在未来几年中遭受大流行的长期后果。