Development of Advanced MRI for the Thoracolumbar Spinal Cord for Clinical Application

项目总结 在多发性硬化症(MS)中，估计40%的脊髓(SC)病变位于胸部和 腰椎节段的SC。SC的这些区域与下肢和膀胱功能有关， 多发性硬化症中最常见的神经功能障碍的靶点，但胸腰椎SC的研究明显不足 而且这里的病变很少用临床磁共振成像(MRI)方案来识别。传统型 胸腰椎SC的临床MRI对可能导致其发生的病变和显微病理缺乏敏感性 损伤，无法辨别脱髓鞘的程度或可能改变的下段脊髓的功能。 该项目的总体目标是开发和优化定量表征的mri方法。 MS患者胸腰椎SC的组织结构和功能的研究我将在三年内完成这一目标 目的：目的1)开发和优化解剖、弥散和静息状态功能磁共振成像方法 临床场强(3T)下的胸腰椎SC，目的2)量化胸腰椎MRI的重复性 在健康志愿者中的方案，并表征生物变异(例如，年龄和性别差异) 胸腰段脊髓的结构和功能，以及目的3)应用多模式MRI工具箱来研究它们之间的关系 MRI指标、生物学变量(年龄、性别)和临床指标之间的关系 多发性硬化症患者的功能障碍。完成这些目标以及临床和免疫学方面的指导培训 此建议书中概述的多发性硬化症的特征将为我提供高级磁共振脉冲的技术培训 脊髓规划和方法的发展，以及扩大免疫学的教学训练， 多发性硬化症的性别差异、神经肌肉生理学和临床治疗。 除了上面的技术专长，这笔赠款将使我过渡到独立的一个 翻译成像科学家。我的机构保证至少90%的受保护时间 研究和职业发展活动。我的专业发展将由一个跨学科的 导师委员会由我的主要导师赛斯·史密斯博士和共同导师约翰·戈尔博士和约翰·戈尔博士领导。 苏布拉曼尼亚姆·斯里拉姆。史密斯博士是脉冲编程和先进核磁共振方法部署方面的专家 Gore博士和Siram博士以他们在生物医学成像方法方面的工作而闻名 以及免疫学因素在MS损伤修复中的应用。我正在利用这一点 Vanderbilt在翻译成像研究和易于获得的临床主题方面的优势 范德比尔特影像科学研究所和临床科室的导师和合作者 大学医学中心。这使得范德比尔特成为一个独特的、具有刺激性的职业环境 发展和完成我提议的研究。

PROJECT SUMMARY In multiple sclerosis (MS), an estimated 40% of spinal cord (SC) lesions are located in the thoracic and lumbar segments of the SC. These regions of the SC are associated with lower limb and bladder function, the most prevalent targets for neurological deficits in MS, but the thoracolumbar SC is significantly understudied and lesions here are rarely identified with clinical magnetic resonance imaging (MRI) protocols. Conventional clinical MRI for the thoracolumbar SC lacks sensitivity to lesions and microscopic pathology that may drive impairment, and is unable to discern the extent of demyelination or possible altered function of the lower cord. The overarching goal of this project is to develop and optimize MRI methods for quantitative characterization of tissue structure and function in the thoracolumbar SC in patients with MS. I will complete this goal in three aims: Aim 1) Develop and optimize anatomical, diffusion, and resting-state functional MRI methods for the thoracolumbar SC at clinical field strength (3T), Aim 2) Quantify the reproducibility of the thoracolumbar MRI protocol in healthy volunteers and characterize biological variation (e.g. age and sex differences) in thoracolumbar cord structure and function, and Aim 3) Apply the multimodal MRI toolset to study relationships between MRI indices, biological variables (age, sex), and clinical measures of lower limb and bladder dysfunction in MS patients. Completion of these aims and the mentored training in clinical and immunological features of MS outlined in this proposal will provide me with technical training in advanced MRI pulse programming and methods development for the spinal cord, and expanded didactic training in immunology, sex differences in MS, neuromuscular physiology, and clinical management of MS. In addition to the technical expertise above, this grant will allow me to transition to independence as a translational imaging scientist. My institution has guaranteed at least 90% protected time to the proposed research and career development activities. My professional development will be guided by an interdisciplinary mentorship committee led by my primary mentor Dr. Seth Smith and co-mentors Dr. John Gore and Dr. Subramaniam Sriram. Dr. Smith is an expert in pulse programming and deployment of advanced MRI methods in clinical populations, and Drs. Gore and Siram are renowned for their work in biomedical imaging methods and applications and immunological factors in MS lesion recovery, respectively. I am capitalizing on Vanderbilt’s strengths in translational imaging research and readily available clinical subjects by working with mentors and collaborators in the Institute of Imaging Science and in clinical departments of the Vanderbilt University Medical Center. This makes Vanderbilt a unique and stimulating environment for professional development and completion of my proposed studies.