EVALUATION OF AXONAL INTEGRITY USING DIFFUSION TENSOR IMAGING

项目摘要 候选人是一名学术神经外科医生，其职业科学目标是了解神经外科手术的机制。 脊髓和周围神经损伤后轴突变性和再生。这位候选人有 重要的实验室经验，有成功发表的轴突研究项目的跟踪记录 损伤和再生。为了准备过渡到成功的独立调查员，候选人的 职业发展计划包括设计成果和临床研究的研究生课程， 临床研究中的流行病学、生物统计学、生物成像技术和遗传学。这将是 辅以神经病学、神经科学和神经疾病希望中心的研讨会， 并在主要的国家和国际会议上介绍候选人的研究。 拟议中的职业发展计划和科学培训将在圣路易斯的华盛顿大学进行， 在神经放射学、先进成像和神经生物学方面具有特殊优势的机构， 候选人与重要的智力援助和合作。科学培训将由 博士Sheng-Kwei Song，他的实验室专注于神经系统的扩散张量成像（DTI）。他 实验室在评估轴突完整性和确定白色物质的定量方法方面的专业知识 连接性以及他对颈椎特定成像方法的了解将为候选人提供 作为一个独立的研究者，研究轴突损伤和白色物质所需的研究工具 脊髓损伤患者的健康状况。 脊髓损伤是一个重大的公共卫生问题。一个主要的缺点限制了改善 脊髓损伤患者的治疗缺乏可量化的指标， 决策先进的MRI技术，如DTI，作为一种非侵入性的检查方法， 创伤性脑损伤的生物标志物。DTI测量水的大小、各向异性和方向性 组织中的位移，并提供沿着白色物质束的方向扩散率的可量化测量。沿着白色物质束的方向扩散率。 DTI指标，如分数各向异性，轴向扩散率和径向扩散率是轴突和轴突的标记。 髓鞘损伤在动物研究中，DTI指标已被证明与以下损伤的严重程度相关： 脊髓损伤在动物模型中，我们已经证明急性DTI测量可以预测长期的 脊髓损伤后的功能结果。这项建议的长期目标是建立和 验证非侵入性成像生物标志物，其是患者临床过程和治疗的预测因子， 脊髓损伤后的反应。第一个目标，将确定DTI参数是否相关 颈髓损伤后的急性神经功能障碍。这一目标将检验以下假设： 急性脊髓损伤引起的原发性轴索损伤，会引起DTI参数的改变， 与急性神经功能相关。本建议的第二个目的，将确定是否脊柱DTI 急性测量的指标，预测颈脊髓损伤后的长期神经学结局。这 目的是检验由急性脊髓损伤引起的轴突损伤产生可测量的 脊髓DTI指标下降，可预测长期功能结果。最终目标是 确定脑和脊柱皮质脊髓束分数各向异性，轴向扩散率， 颈髓损伤患者的径向扩散率值。我们将检验这个假设， 慢性颈脊髓损伤导致脑和脊柱DTI指标的可预测变化， 与长期临床结果相关。 这些非侵入性DTI生物标志物的鉴定和验证将为临床诊断提供指导。 管理，长期预后和家庭咨询。非侵入性生物标志物的验证 预测急性脊髓损伤后的功能恢复将代表一个新的和实质性的 颈髓损伤后的颈椎病进展。

Project Abstract The candidate is an academic neurosurgeon, with a career scientific goal of understanding the mechanisms of axonal degeneration and regeneration following spinal cord and peripheral nerve injury. The candidate has significant prior laboratory experience with a track record of successful published research projects in axonal injury and regeneration. To prepare for the transition to successful independent investigator, the candidate's career development plan includes graduate-level coursework in designing outcomes and clinical research, epidemiology in clinical research, biostatistics, biological imaging technology, and grantsmanship. This will be supplemented with seminars in Neurology, Neurosciences, and the Hope Center for Neurological Disorders, as well as presentation of the candidate's research at major national and international conferences. The proposed career development plan and scientific training will occur at Washington University in St. Louis, an institution with particular strengths in neuroradiology, advanced imaging, and neurobiology, providing the candidate with important intellectual assistance and collaborations. The scientific training will be mentored by Dr. Sheng-Kwei Song, whose laboratory focuses on diffusion tensor imaging (DTI) of the nervous system. His laboratory's expertise in assessing axonal integrity and quantitative methods for determining white matter connectivity as well as his knowledge of cervical spine specific imaging methods will provide the candidate with the research tools needed to succeed as an independent investigator studying axonal injury and white matter integrity in patients with a spinal cord injury. Spinal cord injury is a significant public health problem. A major shortcoming limiting efforts to improve the treatment of patients with spinal cord injuries is the lack of quantifiable metrics on which to base clinical decisions. Advanced MRI techniques, such as DTI have shown tremendous promise as a non-invasive biomarker in traumatic head injury. DTI measures the magnitude, anisotropy, and directionality of water displacement in tissue and provides quantifiable measures of directional diffusivity along white matter tracts. DTI metrics such as fractional anisotropy, axial diffusivity, and radial diffusivity are markers of axonal and myelin damage. In animal studies DTI metrics have been shown to correlate with severity of injury following spinal cord injury. In an animal model we have demonstrated acute DTI measures are predictive of long-term functional outcomes following spinal cord injury. The long-term objective of this proposal is to establish and validate non-invasive imaging biomarkers that are predictors of a patient's clinical course and therapeutic response following a cervical spinal cord injury. The first aim, will determine whether DTI parameters correlate with acute neurologic function following cervical spinal cord injury. This aim will test the hypothesis that primary axonal injury produced by acute spinal cord injury, produces alterations in DTI parameters that correlate with acute neurologic function. The second aim of this proposal, will determine whether spine DTI metrics measured acutely, predict, long-term neurologic outcomes following a cervical spinal cord injury. This aim will test the hypothesis that axonal injury caused by acute spinal cord injury produces a measurable decrease in spinal cord DTI metrics, which are predictive of long-term functional outcomes. The final aim, is to determine the quantitative change in brain and spine corticospinal tract fractional anisotropy, axial diffusivity, and radial diffusivity values in patients with cervical spinal cord injuries. We will test the hypothesis that chronic cervical spinal cord injuries result in predictable changes in both brain and spine DTI metrics that correlate with long-term clinical outcome. The identification and validation of such non-invasive DTI biomarkers will provide guidance on clinical management, long-term prognosis, and family counseling. The validation of a non-invasive biomarker for predicting functional recovery following an acute spinal cord injury would represent a new and substantial advance in prognostication following a cervical spinal cord injury.