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.

项目摘要该建议旨在扩大我们调查人颈脊髓功能连通性的工作（CSC）使用静止状态功能MRI（RSFMRI）将CSC函数与1）结构异常相关联和2）多发性硬化症患者（MS）的临床，神经功能。我们提出了功能连接性通过空间相关的血液氧合水平依赖（粗体）信号可以提供 MS患者的CSC功能，恢复和治疗的空前生物标志物没有无创成像法。大脑中的RSFMRI已被广泛研究，但在CSC中进行了类似的研究缺乏。我们的小组首先报道了检测和数量的空间相关，低频粗体在健康志愿者中，CSC的信号波动在静止状态下，我们在此显示MS患者。我们的科学前提是，MS患者所经历的许多神经系统定义可能来自 SC损坏和静止状态，神经同步的改变负责维持SC 功能将为MS患者中CSC的功能健康提供新颖的客观生物标志物。我们的实验室还为MS中的CSC开创了高级，定量MRI（QMRI），我们将首先时间，相关的QMRI指数的变化反映了轴突和髓磷脂健康，以及病变伯嫩以及组织萎缩以改变静止状态CSC功能。我们建议利用技术发展将最近的工作转变为3T，以及对这些方法的临床验证，以评估 CSC RSFMRI。我们的目标是1）进一步开发可靠的可靠方法来检测和量化功能通过优化3T部署的采集和分析，人类CSC中的连通性，2）与RSFMRI联系结构性异常和QMRI（扩散张量成像和定量磁化转移）和 3）与神经系统障碍和进化相关的RSFMRI畸变。 RSFMRI将与空间有关病变，病变伯嫩和QMRI衍生指数内部和跨CSC段的分布。最后， RSFMRI连接性的测量将与一系列有针对性的神经系统评估相关探究MS患者的神经功能以确定RSFMRI与MS的相关性损害。我们假设增加的结构异常将导致更大的RSFMRI连接性改变，尽管神经系统介绍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功能和结构来理解 MS患者的神经性 - 放射学不一致。如果成功，我们将确定RSFMRI 可以部署大脑的研究来客观地评估CSC中的功能电路和同步并表明从CSC RSFMRI评估得出的措施与评估临床表现有关功能或功能丧失。在静止状态下评估功能连通性的机会进一步对神经功能有限或脊髓主要疾病的患者有益。