Advanced MRI Techniques in Traumatic Brain Injury

描述(申请人提供)：创伤性脑损伤(TBI)是导致残疾、战时和平民创伤的主要原因。目前的临床评估和成像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。这种方法是建立在创伤性轴索损伤是脑损伤后脑功能受损的主要原因的假设基础上的。我们发现，在常规MRI显示正常的区域，DTI可以准确和定量地检测轴突损伤。静息状态fMRI相关性分析可以补充评估轴突损伤的功能后果。我们最初在人类颅脑损伤患者身上的成像经验已经提供了非凡的见解。我们计划对50名具有良好特征的神经和神经心理缺陷的慢性颅脑损伤患者进行初步研究，并对他们进行DTI和静息状态功能磁共振扫描。我们提出了三个目标，旨在验证创伤性轴索损伤是脑损伤后脑功能受损的主要原因这一假设，改进方法，并建立这种先进的MRI方法的临床实用价值。具体目标1：评估这些成像方法在已知对特定神经功能(如运动、感觉、语言、短期记忆)必需的大脑区域观察到的异常是否与先前文献中的神经和神经心理测试定义的缺陷相关。并与相同区域的常规MRI表现进行比较。具体目标2：使用这些先进的成像技术来帮助定位与创伤性脑损伤的常见后遗症相关的损伤，如注意力缺陷障碍，其解剖基础目前尚不完全清楚。具体目标3：确定DTI和静息状态fMRI相关性分析反映的功能性显著轴索损伤的总负荷是否比常规MRI方法检测的病变负荷更准确地反映总体临床结果。如果成功，这种方法可以极大地促进脑外伤患者的治疗开发和管理，减轻这种神经疾病的负担，这是NNDS的关键任务。从长远来看，该项目希望将这些技术应用于其他未被研究的神经系统疾病。公共卫生相关性：DTI和静息状态功能磁共振成像等准确诊断可以改善临床试验、康复和生活规划的分类、分层，从而极大地影响公共健康。

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.