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

描述（由申请人提供）：该提案旨在(1)开发和评估超高场（7特斯拉）下人类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类颈脊髓的功能网络。这些方法可在临床上用于确定脊髓损伤的程度和监测功能恢复的进展，也可促进早期发现中枢神经系统病变，如多发性硬化症。我们建议发展7T功能磁共振成像来检测和量化基线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。迄今为止，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，证明低频BOLD信号波动是正常健康大脑固有的，代表了皮层功能组织的重要水平。然而，到目前为止，还没有相应的研究最终证明在脊髓灰质中存在类似的低频相关性。在过去的二十年里，尽管使用MRI以外的方法研究功能连通性和脊髓可塑性已经成为激烈研究的主题，但正常和病理人群的脊髓的确切功能仍然知之甚少。脊髓功能磁共振成像研究的缺乏主要反映了在脊髓中进行功能磁共振成像的技术困难，未能开发合适的方法和线圈，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。我们假设所提出的技术进步可用于检测和表征颈脊髓的功能连接以及损伤、恢复和修复过程中发生的变化，并且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成像研究。我们建议通过使用超高场（7特斯拉）扫描仪和专用的16通道颈椎线圈来开发（目标1）和验证（目标2）新的fMRI采集和数据校正方案，以满足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阶段的教学培训主要集中在神经科学和神经解剖学上，以培养R00阶段所需的技能，即解释健康对照（Aim 3）和脊髓型颈椎病（Aim 4）受试者的静息状态脊柱网络。7T fMRI的高信噪比和BOLD对比已经显示出比低现场研究在检测大脑高空间分辨率的激活和连接方面的显著优势，并行线圈阵列允许更快的图像采集。因此，超高场MRI具有独特的优势，可以深入了解人类脊髓的功能，这在低场的实践中是不可能的。申请人的长期目标是成为一名独立的成像科学家，专门从事脑和脊髓的功能成像和先进神经成像方法的发展。

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.