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

多发性硬化症颈脊髓的结构和功能 MRI

基本信息

批准号：
10436330
负责人：
Seth A Smith
金额：
$ 34.53万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10436330
关键词：
Address Affect Atrophic Axon Biological Markers Brain Cervical spinal cord structure Childhood Clinical Clinical Research Clinical/Radiologic Data Detection Deterioration Development Diffusion Magnetic Resonance Imaging Disease Evolution Frequencies Functional Magnetic Resonance Imaging Functional disorder Funding Goals Health Horns Human Impairment Injury Lesion Literature Magnetic Resonance Imaging Maintenance Measurement Measures Methods Modeling Motivation Multiple Sclerosis Myelin Nervous System Physiology Nervous System Trauma Neurologic Neurologic Deficit Neurologic Dysfunctions Neuromyelitis Optica Noise Occupations Output Paralysed Pathology Patients Performance Physiological Play Radiology Specialty Recording of previous events Recovery Relapsing-Remitting Multiple Sclerosis Reporting Reproducibility Rest Role Signal Transduction Site Societies Spatial Distribution Spinal Cord Spinal cord damage Spinal cord injury Structural defect Structure Structure-Activity Relationship Testing Time Tissues Translating Translations Transverse Myelitis Trauma Validation Work axon injury blood oxygen level dependent brain magnetic resonance imaging clinically relevant diagnosis evaluation disability emerging adult experience gray matter healthy volunteer human disease human imaging imaging biomarker imaging modality improved indexing loss of function malformation multiple sclerosis patient myelination nervous system disorder neural circuit non-invasive imaging nonhuman primate novel practical application relating to nervous system research study spinal cord compression success white matter

项目摘要

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.

项目概要该提案旨在扩展我们研究人类颈脊髓功能连接的工作 (CSC) 使用静息态功能 MRI (rsfMRI) 将 CSC 功能与 1) 结构异常和 2) 联系起来我们提出多发性硬化症（MS）患者的临床、神经功能连接。通过空间相关的血氧水平依赖（BOLD）信号测量可以提供前所未有的用于多发性硬化症患者 CSC 功能、恢复和治疗的生物标志物，目前有目前还没有对脑部的非侵入性成像方法进行广泛研究，但在 CSC 中也有类似的研究。我们的小组首先报告了空间相关的低频 BOLD 的检测和量化。健康志愿者静息状态下 CSC 的信号波动，我们在本文中展示了多发性硬化症患者的信号波动。我们的科学前提是，多发性硬化症患者所经历的大部分神经功能恶化可能是由于 SC 损伤以及在静息状态下负责维持 SC 的神经同步性的改变功能将为研究 MS 患者 CSC 的功能健康提供一种新颖、客观的生物标志物。我们的实验室还开创了针对 MS 中 CSC 的先进 MRI (qMRI)，我们将首次定量时间、反映轴突和髓磷脂健康状况的 qMRI 指数的相关变化以及病变负担，以及组织萎缩对静息态 CSC 功能的改变我们建议利用技术发展来实现。将最近的工作转变为 3T，并对这些方法进行临床验证，评估其附加价值我们的目标是 1) 开发进一步稳健、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 的连接，2) 关联 rsfMRI 结构和 qMRI（扩散张量成像和定量磁化转移）异常，以及 3) 将 rsfMRI 畸变与神经损伤联系起来，并将 rsfMRI 与空间相关。 CSC 节段内和跨 CSC 节段的病变分布、病变负荷和 qMRI 衍生指数。 rsfMRI 连接性的测量将与一系列有针对性的神经学评估相关联探测多发性硬化症患者的神经系统表现，以确定 rsfMRI 变化与多发性硬化症的相关性我们追求结构异常的增加将导致 rsfMRI 连接性增强。改变，尽管神经学表现可能不那么容易相关，因此，这一点的重要性。建议是我们将首次全面评估CSC的功能和结构，以了解如果成功，我们将建立 rsfMRI 来确定 MS 患者的神经学-放射学不一致。大脑研究可用于客观评估 CSC 内的功能回路和同步性并表明源自 CSC rsfMRI 评估的测量结果与评估临床表现相关功能或功能丧失的机会进一步评估静息状态下的功能连接。对于神经功能有限或患有脊髓主要疾病的患者有益。