Functional Imaging and resting state connectivity in human spinal cord at 7 Tesla

描述(申请人提供)：这项建议旨在(1)开发和评估超高场(7特斯拉)人颈脊髓功能磁共振成像(FMRI)的新方法，以及(2)非侵入性检测和表征人颈脊髓的功能网络。这些方法可用于临床确定脊髓损伤的程度和监测术后功能恢复的进展，还可能有助于早期发现中枢神经系统病变，如多发性硬化症。我们建议开发7T功能磁共振来检测和量化基线BOLD(血氧水平依赖)信号的低频波动，作为脊髓灰质静息状态功能连接的指标。到目前为止，已有超过3500项研究使用类似的fMRI方法来研究大脑的功能连接，并提供了令人信服的证据，表明低频BOLD信号波动是正常、健康的大脑固有的，代表了皮质功能的重要组织水平。然而，到目前为止，还没有相应的研究确凿地证明脊髓灰质存在类似的低频相关性。尽管使用MRI以外的方法研究脊髓的功能连通性和可塑性在过去20年里一直是密集的研究主题，但正常人群和病理人群中脊髓的精确功能仍然知之甚少。脊髓功能磁共振成像研究的匮乏主要反映了在脊髓进行功能磁共振成像的技术困难，未能开发出适当的方法和线圈，以及与大脑相比，脊髓成像需要更高的空间分辨率和更高的灵敏度。我们假设，拟议的技术进步可用于检测和表征颈髓的功能连通性以及损伤、恢复和修复过程中发生的变化，这些测量将补充其他功能测量的信息，包括基于任务的功能磁共振研究。我们建议使用超高场(7特斯拉)扫描仪和专用16通道颈椎线圈来开发(目标1)和验证(目标2)新的功能磁共振成像采集和数据校正协议，以满足对高空间分辨率和更高BOLD灵敏度的需求。申请人是一名计算机/生物医学工程师，因此K99阶段的教学培训侧重于神经科学和神经解剖学，以发展R00阶段所需的技能，即解释健康对照组(目标3)和脊髓型颈椎病患者(目标4)的静息状态脊髓网络。7T功能磁共振成像的高信噪比和大胆对比度已经显示出相对于较低的现场研究在检测大脑高空间分辨率下的激活和连接方面的显著优势，并且并行线圈阵列允许更快的图像采集。因此，超高场磁共振成像是独一无二的，可以提供对人类脊髓功能的洞察，这在低场强的实践中是不可能的。申请者的长期目标是成为一名独立的成像科学家，专门从事大脑和脊髓的功能成像以及先进神经成像方法的开发。

DESCRIPTION (provided by applicant): This proposal aims to (1) develop and evaluate novel methodologies for functional magnetic resonance imaging (fMRI) of the human cervical spinal cord at ultra-high field (7 Tesla), and (2) non-invasively detect and characterize functional networks in the human cervical spinal cord. These methods may be used clinically to establish the extent of spinal cord injuries and to monitor the progression of functional recovery afterwards, and may also facilitate earlier detection of central nervous system pathologies such as multiple sclerosis. We propose to develop 7T fMRI to detect and quantify low-frequency fluctuations in baseline BOLD (blood oxygenation level dependent) signals as indicators of resting state functional connectivity in spinal gray matter. To date, over 3500 studies have used similar fMRI approaches to study functional connectivity in the brain, and have provided compelling evidence that low-frequency BOLD signal fluctuations are inherent in normal, healthy brains and represent an important level of organization of cortical function. However, to date no corresponding studies have conclusively demonstrated similar low-frequency correlations in spinal gray matter. The precise functioning of the spinal cord in normal and pathological populations remains poorly understood even though studies of functional connectivity and spinal cord plasticity using methods other than MRI have been topics of intense research for the past two decades. The scarcity of spinal fMRI studies mainly reflects the technical difficulties of performing fMRI in the spinal cord, the failure to develop appropriate methods and coils, and the need for higher spatial resolution and greater sensitivity for imaging the spinal cord compared to the brain. We hypothesize that the proposed technical advances can be used to detect and characterize functional connectivity in the cervical spinal cord and changes that occur with injury, recovery and repair, and that these measures will complement information from other functional measures including task-based fMRI studies. We propose to address the need for high spatial resolution and greater BOLD sensitivity by using an ultra-high field (7 Tesla) scanner and a dedicated 16-channel cervical spine coil to develop (Aim 1) and validate (Aim 2) novel fMRI acquisition and data correction protocols. The applicant is a computer/biomedical engineer, so didactic training during the K99 phase is focused on neuroscience and neuroanatomy to develop the skills required for the R00 phase, namely interpretation of resting state spinal networks in healthy controls (Aim 3) and subjects with cervical spondylotic myelopathy (Aim 4). The higher signal-to-noise ratio and BOLD contrast from 7T fMRI have already shown significant advantages over lower field studies for detecting activation and connectivity at high spatial resolution in the brain, and parallel coil arrays permit faster image acquisitions. Thus, ultra-high field MRI is uniquely poised to provide insights into human spinal cord function that are not possible in practice at lower fields. The applicant's long term goal is o become an independent imaging scientist specializing in functional imaging of the brain and spinal cord and the development of advanced neuroimaging methods.