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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要自世界卫生组织于 2020 年 3 月宣布 COVID-19 为大流行以来，有证据表明，这种疾病会影响多个器官，包括中枢神经系统（CNS）。通过磁共振在临床上记录了 COVID-19 在急性期对中枢神经系统的影响通过血浆生物标志物和尸检进行成像（MRI）和光谱学（MRS），伴有神经系统症状 1/3至2/3的住院重症病例出现这种情况。急性期过后，大约 10% 的患者经历长期患病，期间出现神经系统症状（头痛、认知迟钝和疲劳）是 COVID-19 幸存者报告的十大症状之一。这些长期的生物学基础症状未知；因此，系统性研究此类疾病的病理生理学的前瞻性研究急需后遗症。根据 COVID-19 的临床表现，数月内的 COVID 相关症状报告感染后，包括帕金森病和其他神经和神经认知延迟的报告并发症范围从轻度到重度，以及已知的脑病理外周触发因素，神经炎症（目标 1）、神经变性（目标 2）和脑血管疾病（CVD）（目标 3）预计将成为长期中枢神经系统病理生理学的重要组成部分。 COVID-BRAIN 高级成像网络 (COVID-BRAIN) 由六家联盟组成系统地、前瞻性地阐明 COVID-19 的长期 CNS 病理生理学的机构使用 3 特斯拉的高度灵敏、协调、先进的 MRI/MRS 技术以及标准化神经学和神经心理学评估以及炎症血液生物标志物。目前有五个站点其他多站点神经影像计划的合作伙伴（明尼苏达大学、梅奥诊所罗切斯特、哈佛大学大学/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、扩散 MRI、磁化率加权 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具有神经系统症状的新冠肺炎后病例 (N=200) 和匹配对照的数据（N=100）。南加州大学神经影像实验室（LONI）将作为数据管理站点。 MR 标记的组间差异和随时间的变化表明神经炎症、神经变性、缺氧/缺血和心血管疾病及其与特定疾病的关系将研究神经系统症状、认知功能和炎症性血液生物标志物。这项研究提供的机制见解将为以下患者的护理和治疗提供信息：预计在未来几年将遭受这一流行病的长期后果。