EVALUATION OF AXONAL INTEGRITY USING DIFFUSION TENSOR IMAGING

应聘者描述(由申请人提供)：应聘者是一名学术神经外科医生，其职业科学目标是了解脊髓和周围神经损伤后轴突退化和再生的机制。应聘者有丰富的实验室经验，有成功发表的轴突损伤和再生研究项目的记录。为了准备过渡到成功的独立研究员，候选人的职业发展计划包括研究生水平的课程设计结果和临床研究，临床研究的流行病学，生物统计学，生物成像技术和工艺。除此之外，还将举办神经学、神经科学和神经疾病希望中心的研讨会，并在主要的国内和国际会议上介绍候选人的研究成果。拟议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，这是一所在神经放射学、高级成像和神经生物学方面具有特殊优势的机构，为应聘者提供重要的智力援助和合作。科学训练将由宋胜贵博士指导，他的实验室专注于神经系统的扩散张量成像(DTI)。他的实验室在评估轴突完整性和确定白质连通性的定量方法方面的专业知识，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名独立研究员成功研究脊髓损伤患者的轴突损伤和白质完整性所需的研究工具。脊髓损伤是一个重大的公共健康问题。限制改善脊髓损伤患者治疗的努力的一个主要缺点是缺乏可用于临床决策的量化指标。先进的磁共振成像技术，如DTI，已显示出作为创伤性颅脑损伤非侵入性生物标志物的巨大前景。DTI测量组织中水置换的大小、各向异性和方向性，并提供沿白质束的定向扩散率的可量化测量。DTI指标，如分数各向异性、轴向扩散系数和径向 弥漫性是轴突和髓鞘损伤的标志。在动物研究中，DTI指标已被证明与脊髓损伤后的损伤严重程度相关。在动物模型中，我们已经证明急性DTI测量可以预测脊髓损伤后的长期功能结果。该提案的长期目标是建立和验证 非侵入性成像生物标志物，可预测患者的临床病程和颈髓损伤后的治疗反应。第一个目标，将决定是否 DTI参数与颈髓损伤后的急性神经功能相关。这一目标将检验一种假说，即急性脊髓损伤引起的原发轴突损伤会导致与急性神经功能相关的DTI参数变化。这项建议的第二个目的，将确定脊柱DTI测量是否能准确地预测颈髓损伤后的长期神经学结果。这一目标将检验一种假设，即急性脊髓损伤引起的轴突损伤会导致脊髓DTI指标的可测量下降，这些指标可以预测长期的功能结果。最终目的是确定大脑和脊柱皮质脊髓束分数的数量变化。 颈髓损伤患者的各向异性、轴向扩散系数和径向扩散系数值。我们将检验这一假设，即慢性颈髓损伤会导致脑和脊柱DTI指标的预测性变化，这与长期临床结果相关。这些非侵入性DTI生物标志物的识别和验证将为临床治疗、长期预后和家庭咨询提供指导。对预测急性脊髓损伤后功能恢复的非侵入性生物标志物的验证将代表着在预测颈髓损伤后的新的实质性进展。

DESCRIPTION (provided by applicant): 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 craftsmanship. 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 pblic 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 predictale 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.