Measuring neuroinflammation in chronic fatigue syndrome with whole-brain magnetic resonance spectroscopy

用全脑磁共振波谱测量慢性疲劳综合征的神经炎症

• 批准号: 9816385
• 负责人: Jarred W. Younger
• 金额: $ 37.97万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9816385
• 关键词: Affect; Age; Anaerobic Bacteria; Astrocytes; Biological Markers; Body mass index; Brain; Brain region; Cells; Cerebrospinal Fluid; Chemicals; Choline; Chronic; Chronic Fatigue Syndrome; Cognitive; Control Groups; Cross-Sectional Studies; Data; Data Set; Development; Diagnosis; Disease; Encephalitis; Etiology; Fatigue; Functional disorder; Glutamates; Glutamine; Goals; Human; Imaging Techniques; Immune; Impaired cognition; Individual; Inflammation; Inositol; Lead; Ligands; Magnetic Resonance Spectroscopy; Measures; Metabolic; Metabolism; Microglia; Moods; N-acetylaspartate; Neurons; Observational Study; Participant; Pathology; Patient Self-Report; Persons; Positron-Emission Tomography; Proteins; Proxy; Research; Research Personnel; Rest; Scanning; Severities; Spinal Puncture; Symptoms; Techniques; Temperature; Testing; United States; Woman; brain tissue; design; glial activation; gray matter; imaging biomarker; interest; longitudinal design; magnetic resonance spectroscopic imaging; neuroimaging; neuroinflammation; pain sensitivity; radioligand; receptor; response; secondary analysis; spectroscopic data; therapy development; tool; uptake; white matter

PROJECT SUMMARY/ABSTRACT In this R01 project, we will test a magnetic resonance spectroscopic imaging (MRSI) technique to assess several markers of neuroinflammation across the entire brain. We will use the technique to investigate the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a condition of unknown etiology that is characterized by profound fatigue not alleviated by rest. The lack of information on ME/CFS pathophysiology has posed a substantial obstacle to the development of treatments that are specific and effective for the disorder. We hypothesize that ME/CFS is the result of low-level inflammation in the brain. Chronic activation of microglia and astrocytes provokes the release of proinflammatory agents that interact with neurons to cause symptoms of fatigue, pain sensitivity, and cognitive and mood disruption. MRSI may be able to detect that neuroinflammation by showing elevated myo-inositol, choline, lactate, brain temperature, and lower N-acetylaspartate that have been associated with abnormal microglia activation. In this five-year R01 study, we will conduct three separate studies. Study #1 examines 90 women with ME/CFS and 30 age- and body mass index-matched healthy controls. Neuroinflammatory markers will be assessed on a voxel-by- voxel basis throughout the entire brain, yielding approximately 4,000 assessments in gray matter, white matter, and cerebrospinal fluid. We hypothesize that the neuroinflammatory markers will be elevated in several brain regions in the ME/CFS group. Study #2 uses a “good-day, bad-day” longitudinal design to examine correlation between neuroinflammatory markers and symptom severity fluctuations in 20 women with ME/CFS. We hypothesize that the higher fatigue severity days will be associated with higher levels of neuroinflammatory markers. In Study #3, we will validate the MRSI scan with positron emission tomography (PET) analysis of 18F-DPA-714, a marker of activated microglia. We expect to see spatial overlap in MRSI and PET indicators of neuroinflammation. Support for these three hypotheses would show that ME/CFS is associated with brain inflammation. This test would allow for safe and inexpensive longitudinal assessment of neuroinflammation that is not possible with positron emission tomography (PET) or lumbar puncture measures of cerebrospinal fluid. Because we collect the entire available spectrum in each voxel, we will also have the first whole-brain metabolic data in ME/CFS. The MRS data can be used to quantify other markers of interest to ME/CFS researchers, such as glutamate and glutamine. We will therefore make the entire dataset available to other researchers for secondary analyses. Ultimately, we hope this non-invasive scanning technique will aid in ME/CFS diagnosis, treatment decisions, and the development of new treatments.

项目摘要/摘要 在此R01项目中，我们将测试磁共振光谱成像（MRSI）技术来评估 整个大脑中神经炎症的几个标记。我们将使用该技术调查 肌动脑脊髓炎/慢性疲劳综合征（ME/CFS）的病理生理学，这是未知状态 病因的特征是深刻的疲劳并不能被静止缓解。缺乏有关我/CFS的信息 病理生理学已经为开发特定治疗的发展带来了重大障碍 对疾病有效。我们假设ME/CFS是大脑低水平炎症的结果。 小胶质细胞和星形胶质细胞的慢性激活引起了相互作用的促炎剂的释放 神经元引起疲劳，疼痛敏感性以及认知和情绪破坏的症状。 MRSI可能是 可以通过显示升高的肌醇，胆碱，鞋底，脑温度， 和较低的N-乙酰天冬氨酸与异常小胶质细胞活化有关的n-乙酰天冬氨酸。在这个五年 R01研究，我们将进行三项单独的研究。研究＃1考试90名与我/CFS的女性和30岁的女性 和体重指数匹配的健康对照。神经炎症标志物将在逐素上进行评估 在整个大脑中的体素基础，在灰质中产生约4,000次评估 物质和脑脊液。我们假设神经炎症标记将升高 ME/CFS组的几个大脑区域。研究＃2使用“美好的一天，糟糕的一天”纵向设计 20名女性的神经炎症标记和症状严重程度波动之间的检查相关性 我/CFS。我们假设较高的疲劳严重性日将与较高的水平有关 神经炎症标记。在研究＃3中，我们将使用正电子发射断层扫描验证MRSI扫描 （PET）分析18F-DPA-714，这是活化小胶质细胞的标记。我们希望看到MRSI的空间重叠 和神经炎症的宠物指标。支持这三个假设将表明我/CFS是 与大脑感染有关。该测试将允许对安全且廉价的纵向评估 通过阳性发射断层扫描（PET）或腰椎穿刺测量不可能的神经炎症 脑脊液的液体。因为我们收集每个体素中的全部可用频谱，所以我们还将拥有 ME/CFS中的第一个全脑代谢数据。 MRS数据可用于量化其他感兴趣的标记 对我/CFS研究人员，例如谷氨酸和谷氨酰胺。因此，我们将使整个数据集可用 给其他研究人员进行次要分析。最终，我们希望这种非侵入性扫描技术将有助于 在ME/CFS诊断，治疗决策和新治疗的发展中。