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

项目摘要 在多发性硬化症（MS）中，估计40%的脊髓（SC）病变位于胸部， SC的这些区域与下肢和膀胱功能相关， MS神经功能缺损的最常见靶点，但胸腰椎SC的研究明显不足 临床磁共振成像（MRI）方案很少识别此处的病变。常规 胸腰椎SC的临床MRI对病变和显微病理学缺乏敏感性， 损伤，并且不能辨别脱髓鞘的程度或下脊髓的可能改变的功能。 该项目的首要目标是开发和优化MRI定量表征方法 的组织结构和功能在MS患者的胸腰椎SC。我将完成这一目标在三个 目的：目的1）开发和优化解剖，弥散和静息态功能MRI方法，用于 临床场强（3T）下的胸腰椎SC，目标2）量化胸腰椎MRI的再现性 在健康志愿者中的方案，并表征生物学变异（例如年龄和性别差异）， 胸腰段脊髓结构和功能，目的3）应用多模式MRI工具集研究关系 MRI指数、生物学变量（年龄、性别）和下肢和膀胱的临床测量之间的关系 MS患者的功能障碍。完成这些目标和临床和免疫学方面的指导培训 本提案中概述的MS功能将为我提供高级MRI脉冲方面的技术培训 脊髓的编程和方法开发，以及扩大免疫学的教学培训， MS、神经肌肉生理学和MS临床管理的性别差异。 除了上述的技术专长，这笔赠款将使我能够过渡到独立作为一个 翻译成像科学家我的机构已经保证至少90%的保护时间，以拟议的 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博士。 Subramaniam Sriram.史密斯博士是脉冲编程和先进MRI方法部署方面的专家 戈尔博士和西拉姆博士以其在生物医学成像方法方面的工作而闻名 以及免疫因素在MS损伤修复中的应用。我在利用 范德比尔特的优势，在转化成像研究和现成的临床科目，通过与 导师和合作者在成像科学研究所和临床部门的范德比尔特 大学医学中心。这使得范德比尔特成为一个独特的和刺激的环境，专业 发展和完成我的研究计划。

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.