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Causal connectivity along the spinal cord using high-resolution 7T fMRI

使用高分辨率 7T fMRI 观察脊髓的因果连接

基本信息

批准号：
10193367
负责人：
Robert L Barry
金额：
$ 46.2万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-21 至 2023-07-20
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10193367
关键词：
Address Amyotrophic Lateral Sclerosis Anatomy Architecture Bilateral Biological Markers Biology Brain Brain Diseases Brain region Central Nervous System Diseases Cervical spinal cord structure Characteristics Communication Communities Complex Data Development Diagnosis Disease Dorsal Fingers Functional Imaging Functional Magnetic Resonance Imaging Future Grain Horns Human Image Imaging Techniques Impairment Left Light Limb structure Magnetic Resonance Imaging Measurement Measures Methodology Methods Modeling Motor Motor Cortex Multiple Sclerosis Neurology Neurons Neurosciences Noise Paper Participant Pathologic Pattern Population Prediction of Response to Therapy Prognosis Protocols documentation Publishing Reproducibility Reproducibility of Results Research Research Personnel Resolution Rest Sampling Scanning Sensory Signal Transduction Spinal Spinal Cord Spinal Cord Diseases Spinal cord injury Structure of postcentral gyrus System Techniques Technology Testing Time Traction Translating Vertebral column Work base chronic pain clinical Diagnosis clinical application dorsal horn gray matter improved insight interest nervous system disorder neuroimaging novel relating to nervous system response somatosensory spinal cord imaging spine bone structure technology/technique temporal measurement

项目摘要

PROJECT SUMMARY / ABSTRACT This proposal aims to (1) develop and validate high spatial and temporal resolution acquisition of functional magnetic resonance imaging (fMRI) in the human cervical spinal cord (C-spine) at ultra-high field (7 Tesla), and (2) non-invasively detect and characterize directional spinal cord networks using fMRI during both rest and task. These methods may find clinical application in central nervous system (CNS) diseases involving the spinal cord. Studying spinal cord function using fMRI has gained traction in the past decade. As of today, we know from fMRI functional connectivity (FC) studies that the left and right dorsal horns are connected (so are left/right ventral horns) within the same vertebral level, but no connection exists between dorsal-ventral horns or between levels. We do not understand why this is the case, and this puzzle has intrigued spinal cord researchers. FC only measures co-activation between spinal regions, and we argue that this traditional approach has not provided us with a comprehensive picture of spinal cord’s functional architecture. We propose to solve this conundrum by measuring directional effective connectivity (EC) among spinal regions instead of co-activation (FC). This choice is supported by the underlying anatomy. The ventral horns carry efferent motor signals from motor cortex down to higher vertebral levels and then to lower ones, while dorsal horns carry afferent somatosensory signals up from lower to higher levels and then to the postcentral gyrus. Corroborating this innate biology, we propose the existence of higher-to-lower EC in ventral and lower-to-higher EC in dorsal horns of the C-spine. Addressing this central question is critical for developing mechanistic models of healthy spinal cord function and subsequently its disruption in disorders of the spinal cord. We aim to take a step toward addressing this issue here. For the first time in the field of spinal cord imaging, we propose (Aim 2) to develop a template of EC in the healthy human C-spine and compare it with the FC template during rest. Furthermore, since resting state primes task responses, we propose to validate the existence of such resting-state EC patterns while participants engage in a simple bilateral finger tapping task (Aim 3). This aim will be achieved through dynamic EC modeling to capture EC patterns specifically during the motor task blocks. Participants will be scanned twice 4 weeks apart to ascertain test-retest reliability and reproducibility of the findings. These techniques require high temporal resolution to identify directional influence of one region over the other as well as capture fast dynamic EC transitions, but also require high spatial resolution to measure the narrow spinal gray matter. Thus, for the first time, we will also develop and validate sub-second and sub-millimeter fMRI acquisition protocols to image the C-spine at ultra-high field of 7T (Aim 1). In the future, we plan to utilize the developmental work from this proposal to study disorders involving the cord. The technology, techniques and mechanistic understanding developed thorough this project has potential for superior diagnosis, disease tracking and prediction of treatment response in CNS disorders such as multiple sclerosis, amyotrophic lateral sclerosis, chronic pain and spinal cord injury.

项目摘要/摘要该建议的目的是(1)开发和验证高空间和时间分辨率的函数的采集在超高场(7特斯拉)下对人颈脊髓(C-脊柱)进行磁共振成像(FMRI)，以及 (2)利用fMRI对静息状态和任务状态下的脊髓定向网络进行无创性检测和表征。这些方法可能在中枢神经系统(CNS)累及脊髓的疾病中得到临床应用。在过去的十年里，使用功能磁共振成像研究脊髓功能得到了越来越多的关注。从今天起，我们从 FMRI功能连接性(FC)研究左右背角(左/右腹角)是相连的角)位于同一椎体水平内，但背角和腹角之间或节段之间没有联系。我们不明白为什么会这样，这个谜题引起了脊髓研究人员的兴趣。仅限FC 测量脊髓区域之间的共同激活，我们认为这种传统的方法并没有为我们提供以及脊髓功能结构的全面图景。我们建议通过以下方式解决这一难题测量脊髓区域之间的定向有效连接(EC)，而不是共激活(FC)。这一选择有潜在的解剖学支持。腹角从运动皮质向下传递传出的运动信号。到较高的脊椎水平，然后到较低的脊椎水平，而背角则将传入的躯体感觉信号向上传递从低到高再到中央后回。为了证实这一先天生物学，我们提出了 C-棘背侧角存在由高到低的EC和由低到高的EC。解决这个问题中心问题是开发健康脊髓功能的机制模型的关键，并随后它在脊髓疾病中的破坏。我们的目标是在这里朝着解决这个问题迈出一步。在脊髓成像领域，我们首次提出(目标2)在脊髓成像中开发EC模板。健康人C-脊柱，休息时与FC模板进行比较。此外，由于静止的州素数任务反应，我们建议在参与者参与时验证这种静息态EC模式的存在在一个简单的双边手指敲击任务中(目标3)。这一目标将通过动态EC建模来实现在运动任务块中捕获特定的EC模式。参与者将每隔4周接受两次扫描以确定重测结果的可靠性和重复性。这些技术需要很高的时间性分辨率以确定一个区域对另一个区域的方向性影响，并捕获快速动态EC 过渡，但也需要高空间分辨率来测量狭窄的脊髓灰质。因此，对于第一个时间，我们还将开发和验证亚秒和亚毫米fMRI采集协议，以成像 7T超高场的C-脊柱(目标1)。在未来，我们计划利用这一提案的开发工作研究涉及脐带的疾病。发展出的技术、技巧和机械理解该项目具有卓越的诊断、疾病跟踪和治疗反应预测的潜力。治疗中枢神经系统疾病，如多发性硬化症、肌萎缩侧索硬化症、慢性疼痛和脊髓损伤。