Structural and Functional MRI of the Cervical Spinal Cord in Multiple Sclerosis

项目摘要 这项建议旨在扩展我们研究人类颈髓功能连接的工作 (CSC)使用静息状态功能磁共振成像(RsfMRI)将CSC功能与1)结构异常和2) 多发性硬化(MS)患者的临床和神经功能。我们提出功能连通性 如由空间相关的血氧水平依赖(BOLD)信号测量的，可以提供 用于MS患者CSC功能、康复和治疗的前所未有的生物标记物，目前有 无非侵入性成像方法。Rsfmri在大脑中已经得到了广泛的研究，但在CSC进行了类似的研究。 都是缺乏的。我们小组首次报道了空间相关低频BOLD的检测和量化 健康志愿者静息状态下CSC的信号波动，我们在此展示了MS患者的信号波动。 我们的科学假设是，多发性硬化症患者经历的大部分神经恶化可能源于 SC损伤和静息状态下，负责SC维持的神经同步性改变 Function将为研究MS患者CSC的功能健康状况提供一种新的、客观的生物标志物。 我们的实验室还率先为MS的CSC提供了先进的定量磁共振成像(QMRI)，我们将首次 时间，反映轴突和髓鞘健康的qMRI指数的相关变化，以及病变负荷 组织萎缩到静息状态的CSC功能改变。我们建议利用技术发展来 将最近的工作过渡到3T，并对这些方法进行临床验证，以评估 CSC rsfMRI。我们的目标是1)进一步开发健壮、可靠的方法来检测和量化功能 通过优化3T部署的采集和分析来实现人类CSC的连通性，2)与rsfMRI相关 结构和qMRI(扩散张量成像和定量磁化转移)的异常，以及 3)将rsfMRI异常与神经功能损害和进化联系起来。RsfMRI将与空间相关 病变在CSC节段内和跨CSC节段的分布、病变负荷和qMRI衍生指数。最后， Rsfmri连通性的测量将与一系列有针对性的神经评估相关。 探讨多发性硬化症患者的神经表现以确定rsfMRI改变与多发性硬化症的相关性 减损。我们假设增加的结构异常将导致更强的rsfmri连通性。 改变，尽管神经表现可能不那么容易相关。因此，这一点的意义 建议是，我们将首次全面评估CSC的功能和结构，以了解 多发性硬化症患者的神经-放射学不一致如果成功，我们将建立rsfMRI 对大脑的研究可以客观地评估CSC内的功能回路和同步性 并表明csc rsfmri评估方法对临床表现的评估是相关的。 功能或丧失功能。在休眠状态下评估功能连通性的机会进一步 适用于神经功能受限或患有以脊髓为主的疾病的患者。

Project Summary This proposal aims to extend our work investigating functional connectivity in the human cervical spinal cord (CSC) using resting state functional MRI (rsfMRI) to relate CSC function to 1) structural abnormalities and 2) clinical, neurological function in patients with multiple sclerosis (MS). We propose that functional connectivity as measured by spatially correlated blood oxygenation level dependent (BOLD) signals may provide an unprecedented biomarker for CSC function, recovery, and treatment in MS patients, for which there is currently no non-invasive imaging method. rsfMRI in the brain has been widely studied, yet similar studies in the CSC are lacking. Our group first reported detection and quantification of spatially correlated, low-frequency BOLD signal fluctuations in the CSC in a resting state in healthy volunteers and we show, herein, in patients with MS. Our scientific premise is that much of the neurological deterioration experienced by MS patients may arise from SC damage and in the resting state, alterations in neural synchrony responsible for maintenance of SC function will provide a novel, objective biomarker for studying the functional health of the CSC in MS patients. Our lab has also pioneered advanced, quantitative MRI (qMRI) for the CSC in MS, and we will, for the first time, relate changes in qMRI indices reflective of axonal and myelin health, as well as lesion burden, and tissue atrophy to alterations in resting-state CSC function. We propose to utilize technical developments for transitioning recent work to 3T, and also clinical validation of these approaches assessing the added value of CSC rsfMRI. We aim to 1) further develop robust, reliable methods to detect and quantify functional connectivity in the human CSC by optimizing acquisition and analysis for 3T deployment, 2) to relate rsfMRI abnormalities to structural, and qMRI (Diffusion Tensor Imaging and Quantitative Magnetization Transfer), and 3) to relate rsfMRI aberrations to neurological impairment, and evolution. rsfMRI will be related to spatial distribution of lesions, lesion burden, and qMRI-derived indices within and across CSC segments. Lastly, measurements of rsfMRI connectivity will be correlated with a battery of targeted neurological assessments that probe an MS patient’s neurological performance to establish the relevance of rsfMRI changes to MS impairment. We hypothesize that increased structural abnormalities will result in greater rsfMRI connectivity alterations, though neurological presentation may not be as easily related. Therefore, the significance of this proposal is that we will, for the first time, comprehensively assess CSC function and structure to understand the neurological-radiological discordance in patients with MS. If successful, we will establish that rsfMRI studies of the brain can be deployed to objectively evaluate functional circuitry and synchrony within the CSC and show that measures derived from CSC rsfMRI assessment are relevant for assessing clinically manifest function, or loss of function. The opportunity to assess functional connectivity in the resting state has further benefit in patients who have limited neurological function or present with spinal cord predominant disease.