EVALUATION OF AXONAL INTEGRITY USING DIFFUSION TENSOR IMAGING

使用扩散张量成像评估轴突完整性

• 批准号: 8616148
• 负责人: Wilson Z Ray
• 金额: $ 17.2万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8616148
• 关键词: Activities of Daily Living; Acute; Address; Adult; American; Animal Model; Animals; Anisotropy; Biological; Biological Markers; Biometry; Bone Tissue; Brain; Cervical; Cervical spinal cord injury; Cervical spine; Chronic; Clinical; Clinical Management; Clinical Research; Clinical Trials; Collaborations; Corticospinal Tracts; Counseling; Craniocerebral Trauma; Denervation; Development Plans; Diffusion Magnetic Resonance Imaging; Disease; Epidemiology; Evaluation; Family; Future; Goals; Health; Human; Image; Imaging Techniques; Imaging technology; Injury; Institution; International; Knowledge; Laboratories; Left; Magnetic Resonance Imaging; Measurable; Measures; Mentors; Methods; Metric; Morphologic artifacts; Myelin; Natural regeneration; Nervous System Physiology; Nervous system structure; Neurobiology; Neurologic; Neurological outcome; Neurology; Neurosciences; Neurosurgeon; Outcome; Outcomes Research; Paralysed; Patient Selection; Patients; Peripheral nerve injury; Physiological; Predictive Value; Protocols documentation; Public Health; Publishing; Quadriplegia; Radial; Recovery of Function; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Rodent Model; Scanning; Severities; Soft Tissue Injuries; Spinal Cord; Spinal Injuries; Spinal cord injury; Techniques; Testing; Therapeutic; Therapeutic Intervention; Tissues; Training; Universities; Validation; Vertebral column; Washington; Water; Work; X-Ray Computed Tomography; axon regeneration; axonal degeneration; base; career; career development; design; disability; experience; functional improvement; functional outcomes; imaging modality; improved; insight; multidisciplinary; nervous system disorder; neuroimaging; neurological recovery; outcome forecast; public health relevance; research study; response; spinal cord white matter; symposium; tool; white matter; white matter injury

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.

项目摘要 应聘者是一名学术神经外科医生，职业科学目标是了解脑血管疾病的机制。 脊髓和周围神经损伤后轴突的变性和再生。候选人有 有丰富的实验室经验，有成功发表的轴突研究项目的记录 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结果和临床研究方面的研究生课程， 流行病学：临床研究、生物统计学、生物成像技术和医疗技术。这将是 辅以神经学、神经科学和希望神经疾病中心的研讨会，如 以及在重要的国内和国际会议上展示候选人的研究成果。 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， 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，提供 有重要的智力帮助和合作的候选人。科学训练将由以下人员指导 宋胜贵博士，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的定量方法方面的专业知识 连通性以及他对颈椎特定成像方法的知识将为应聘者提供 作为研究轴突损伤和白质的独立调查者，需要成功的研究工具 脊髓损伤患者的完整性。 脊髓损伤是一个重大的公共卫生问题。一个主要缺陷限制了改善 脊髓损伤患者的治疗缺乏可作为临床依据的量化指标 决定。先进的磁共振成像技术，如DTI，已经显示出作为非侵入性检查的巨大前景 创伤性颅脑损伤的生物标志物。DTI测量水的大小、各向异性和方向性 并提供了沿白质束的定向扩散率的可量化测量。 弥散张量成像分数各向异性、轴向弥散系数和径向弥散系数是轴突和 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 脊髓损伤后的功能结果。这项提议的长期目标是建立和 验证可预测患者临床病程和治疗的非侵入性成像生物标志物 颈髓损伤后的反应。第一个目标将确定DTI参数是否与 颈髓损伤后有急性神经功能障碍。这一目标将检验这一假设 由急性脊髓损伤引起的原发轴突损伤，导致DTI参数改变， 与急性神经功能相关。这项提议的第二个目标，将决定脊柱DTI 测量指标敏锐地预测颈髓损伤后的长期神经学结果。这 Aim将检验这一假设，即急性脊髓损伤引起的轴突损伤产生可测量的 脊髓DTI指标的下降，这是预测长期功能结果的指标。最终的目标，是 测定脑和脊柱皮质脊髓束各向异性分数、轴向弥散系数、 颈髓损伤患者的放射状弥散系数值。我们将检验这一假设 慢性颈髓损伤导致脑和脊柱DTI指标发生可预测的变化 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提供指导 管理、长期预后和家庭咨询。一种非侵入性生物标志物在临床中的应用 预测急性脊髓损伤后的功能恢复将代表着一种新的和实质性的 颈髓损伤后预后的研究进展。