Structural and metabolic neuroimaging of ME/CFS occurring with and without COVID-19 infection

项目摘要 大量和越来越多的患者感染了SARS-CoV-2，该病毒导致 COVID-19，继续经历一系列症状， 初始疾病（长期COVID）。最常报告的症状是疲劳、运动后不适 和认知功能障碍，这是肌痛性脑脊髓炎/慢性疲劳的主要症状 综合征（ME/CFS）。临床上，许多长期COVID患者符合ME/CFS的诊断标准。邮政 随着新冠肺炎大流行，我们预计将看到越来越多的人患有长期COVID ME/CFS。一个重要 问题是COVID ME/CFS患者是否与非COVID ME/CFS患者基本相同， 应该进行类似的评估和处理。如果是这样的话，这组COVID相关患者的CFS可以告诉我们 一般ME/CFS的特征和机制。尽管有人认为大脑是 负责这两种形式的ME/CFS，目前尚未确定特定的神经影像生物标志物。在 本项目，我们的目标是进行全面的神经磁共振成像（MRI），以比较 长期COVID和经典ME/CFS患者之间的相似性和差异，以及与非 受ME/CFS影响，在脑解剖和代谢特征方面。超高场MRI检查，如 7特斯拉，提供了精致的分辨率，可以阐明大脑结构的细微异常。我们将应用 先进的7特斯拉MRI神经成像技术，检查大脑和脑干。超越结构 有限的研究表明，脑血流量的改变和心室乳酸的增加， ME/CFS患者比久坐对照组提示灌注和氧代谢特性可能发生改变 在ME/CFS。本项目的另一个研究重点是评估ME/CFS体内氧代谢的变化 使用基于MRI的方法。我们将测量矢状窦静脉血中的氧气水平， 使用先进的核磁共振成像技术来测量全球脑血流。利用这些参数，我们可以计算出 大脑中的氧代谢率，可以告诉我们是否存在能量衰竭， ME/CFS和长期COVID患者，如先前假设的那样。最后，结构体积和 通过MRI测量的代谢参数将与患者自我报告的症状负担相关， 多维疲劳水平完成这项及时的研究将提供COVID和非COVID的比较 ME/CSF在脑解剖特征和氧代谢特性的变化方面，以及这些变化如何影响脑组织的功能。 影像学参数与疾病负担有关。从结构和代谢方面学到的知识 研究将加深我们对ME/CFS/长期COVID疾病机制的理解，帮助ME/CFS诊断， 为治疗决策提供信息并激发新的治疗目标。

Project Summary A large and increasing number of patients who have been infected with SARS-CoV-2, the virus that causes COVID-19, continue to experience a constellation of symptoms long past the time that they have recovered from the initial illness (long-COVID). The most frequently reported symptoms were fatigue, post exertional malaise and cognitive dysfunction, which are the main symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Clinically, many long-COVID patients fulfill the diagnostic criteria for ME/CFS. Post pandemic, we expect to see an increasing number of individuals with long-COVID ME/CFS. An important question is whether those with COVID ME/CFS are essentially the same as those with non-COVID ME/CFS and should be evaluated and treated similarly. If so, this group of COVID-related patients’ CFS could inform us about the features and mechanisms of ME/CFS in general. Although it was suggested that the brain is the organ responsible for both forms of ME/CFS, currently no specific neuroimaging biomarkers have been identified. In this project, we aim to conduct comprehensive neurological magnetic resonance imaging (MRI) to compare the similarities and differences between long-COVID and classic ME/CFS patients, as well as to individuals not affected by ME/CFS, in terms of brain anatomical and metabolic features. MRI exams at ultra-high field, such as 7 Tesla, offers exquisite resolution and can elucidate subtle abnormalities in the brain structure. We will apply advanced 7 Tesla MRI neuroimaging techniques to exam the cerebrum and brainstem. Beyond structural changes, limited studies have shown altered cerebral blood flow and increased cerebroventricular lactate in ME/CFS patients than sedentary controls suggesting perfusion and oxygen metabolic properties might be altered in ME/CFS. Another research focus of this project is to assess changes in oxygen metabolism of ME/CFS in vivo using MRI based methods. We will be measuring the oxygen level in the venous blood of sagittal sinus and the global cerebral blood flow using advanced MRI techniques. Using these parameters, we can calculate the global cerebral metabolic rate of oxygen in the brain which can inform us on whether energy failure is present in individuals with ME/CFS and long-COVID, as previously postulated. Finally, the structural volumetric and metabolic parameters measured by MRI will be correlated with patients’ self-reported symptom burden and multidimensional fatigue level. Completion of this timely study will provide comparison of COVID and non-COVID ME/CSF in terms of changes in brain anatomical features and oxygen metabolic properties, as well as how these imaging parameters are related to the disease burden. The knowledge learned from the structural and metabolic study will deepen our understanding the ME/CFS/long-COVID disease mechanisms, aid in ME/CFS diagnosis, inform treatment decisions and inspire new treatment targets.