Advanced MRI Techniques in Traumatic Brain Injury

描述（由申请人提供）：创伤性脑损伤（TBI）是战时和平民创伤致残的主要原因。目前的临床评估和影像学不能总是可靠地确定损伤的存在和严重程度。我们建议使用两种先进的MRI方法-扩散张量成像（DTI）和静息状态fMRI相关分析-来解决这些问题。这种方法是基于创伤性轴索损伤是脑外伤后脑功能受损的主要原因的假设。我们发现DTI可以准确定量地检测常规MRI显示正常的轴突损伤区域。静息状态fMRI相关分析可以补充评估轴突损伤的功能后果。我们对人类创伤性脑损伤患者的初步成像经验已经提供了非凡的见解。我们计划对50例具有明确特征的神经和神经心理缺陷的慢性TBI患者进行初步研究，并对他们进行DTI和静息状态功能MRI扫描。我们提出了三个目标，旨在验证创伤性轴索损伤是脑外伤后脑功能受损的主要原因的假设，完善方法，并建立这种先进的MRI方法的临床应用。具体目标1：评估这些成像方法在特定神经功能（如运动、感觉、语言、短期记忆）所必需的大脑区域观察到的异常是否与先前记录的神经和神经心理学测试所定义的缺陷相关。将在同一区域与常规MRI结果进行比较。具体目标2：利用这些先进的成像技术来帮助定位与创伤性脑损伤常见后遗症相关的损伤，如注意缺陷障碍，其解剖学基础目前尚不完全清楚。具体目标3：确定DTI和静息状态fMRI相关分析所反映的功能显著轴突损伤的总负担是否比传统MRI方法检测的病变负担更准确地反映了整体临床结果。如果成功，该方法可以显著促进TBI患者的治疗开发和管理，减轻这种神经系统疾病的负担，这是NNDS的一项关键任务。从长远来看，该项目希望将这些技术应用于其他未充分研究的神经系统疾病。公共卫生相关性：像DTI和静息状态功能磁共振成像这样的准确诊断可以改善临床试验的分类、分层、康复和生活规划，对公共卫生产生重大影响。

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a major cause of disability wartime and civilian trauma. Current clinical assessments and imaging cannot always reliably determine the presence and severity of injury. We propose to use two advanced MRI methods- diffusion tensor imaging (DTI), and resting-state fMRI correlation analysis- to address these issues. This approach is based on the hypothesis that traumatic axonal injury is a principal cause of impaired brain function following TBI. We have found that DTI accurately and quantitatively detects axonal injury in areas where conventional MRI appears normal. Resting-state fMRI correlation analysis may complementarily allow assessment of the functional consequences of axonal injury. Our initial imaging experience in human TBI patients has already provided remarkable insights. We plan to conduct a pilot study of 50 chronic TBI patients with well-characterized neurological and neuropsychological deficits and scan them with DTI and resting-state functional MRI. We propose 3 aims, designed to test the hypothesis that traumatic axonal injury is a principal cause of impaired brain function following TBI, refine the methods, and establish the clinical utility of this advanced MRI methods. Specific Aim 1: To assess whether abnormalities observed with these imaging methods in brain regions known to be necessary for specific neurological functions (e.g. motor, sensory, language, short-term memory) correlate with deficits defined by previously documented neurological and neuropsychological testing. Comparison to conventional MRI findings in the same regions will be made. Specific Aim 2: To use these advanced imaging techniques to help localize injuries associated with common sequelae of traumatic brain injury such as attention deficit disorder whose anatomical substrates are currently not entirely known. Specific Aim 3: To determine whether the total burden of functionally significant axonal injury as reflected by DTI and resting-state fMRI correlation analysis more accurately reflects overall clinical outcome than lesion burden detected by conventional MRI methods If successful, this approach could dramatically enhance therapeutic development and management of TBI patients reducing the burden of this neurological disorder, a key mission of NNDS. Long term, it is the hope of this project to apply these techniques to other understudied neurological conditions. PUBLIC HEALTH RELEVANCE: Accurate diagnostics like DTI and resting-state fMRI could improve triage, stratification for clinical trials, rehabilitation and life-planning, substantially impacting public health.