A Longitudinal Multi-modal Neuroimaging Investigation of Functional Recovery afte

说明(申请人提供)：创伤性脑损伤(TBI)是年轻人长期残疾的一个主要原因，这一事实突显了将应对TBI概念化为终身康复和康复过程的必要性。成功表征康复过程中的神经病理标记物将成为开发更有效的预测和干预的关键步骤。虽然已经确定的是，在受伤后的几个月甚至几年里，行为结果测量显示出显著的改善，但这种恢复的潜在神经机制还不是很清楚。随着活体神经成像的最新进展，现在有可能更准确地测量最初的损伤病理，并以纵向设计阐明自然恢复过程的机制。然而，图像分析方面的挑战阻碍了TBI研究人员充分利用新的成像方式。脑外伤神经影像研究中的几个主要数据分析问题是：1)量化弥漫性和局灶性损伤的后果，2)将不同类型的大脑登记到一个共同的空间，以及3)评估结构-功能关系(例如，失语)。我们最近已经证明了应用高维大变形图像配准方法解决这些方法学挑战的可行性，以前所未有的精度识别了显示对照和脑损伤之间结构和功能基团差异的区域。在这些前期工作的基础上，本项目的目标是：1)确定与中、重度弥漫性轴索损伤相关的结构和功能成像指标的纵向变化模式及其与行为改善的关系；2)利用急性期早期的纵向变化建立基于神经病理学的损伤严重程度测量；3)根据损伤后不同时间点获得的结构和功能成像测量的完整性之间的差异，开发结构-功能差异指数，并收集关于其与行为恢复关系的初步数据。我们建议在多个时间点(自受伤之日起3、6和12个月)采用结构性(大体体积变化和白质完整性)和功能(脑灌注和功能连通性)神经成像测量来评估60例中到重度弥漫性脑损伤患者的急性期。为了进行比较，将对36名人口统计学上匹配的健康对照受试者进行评估。为了衡量行为的纵向改善，将在每个时间点进行全球行为结果测量和由五项执行功能测试组成的神经心理测试组。

DESCRIPTION (provided by applicant): The fact that traumatic brain injury (TBI) is a major cause of long-term disability for young adults underscores the need to conceptualize coping with TBI as a life-long process of recovery and rehabilitation. Successful characterization of neuropathologic markers over the evolving course of recovery will become an essential step toward developing more effective prognostication and intervention. While it is well established that behavioral outcome measures show significant improvements over months and even years after the injury, the underlying neural mechanisms of such recovery are not well understood. With the recent advances of in vivo neuroimaging, it may now be possible to more accurately measure the initial injury pathology and to shed light on the mechanisms of the natural recovery process in a longitudinal design. However, challenges in image analyses have hampered TBI researchers from taking full advantage of new imaging modalities. Several major data analysis issues in TBI neuroimaging research are: 1) quantifying the consequences of diffuse and focal injuries, 2) registering heterogeneous brains into a common space, and 3) assessing structure-function relationship (e.g., diaschisis). We have recently demonstrated the feasibility of applying high-dimensional large deformation image registration method in solving these methodological challenges, identifying the regions showing structural and functional group differences between controls and TBI with unprecedented precision. Based on these preliminary work, the current project aims 1) to determine the pattern of longitudinal changes in structural and functional neuroimaging indices associated with moderate to severe diffuse axonal injury and their relationship with behavioral improvements, 2) to develop a neuropathologically based injury severity measure using longitudinal changes in the early post-acute phase, and 3) to develop a "structure-function discrepancy" index, based on the difference between the integrity of structural and functional imaging measures obtained at different points of post-injury, and collect preliminary data on its relationship with behavioral recovery. We propose to evaluate 60 individuals with moderate to severe diffuse TBI in the post-acute phase with structural (gross volume change and white matter integrity) and functional (cerebral perfusion and functional connectivity) neuroimaging measures at multiple time points (3, 6, and 12 months from the date of injury). Thirty six demographically matched healthy control subjects will be evaluated for comparison purposes. To measure longitudinal improvements in behavior, a global behavioral outcome measure and a neuropsychological test battery consisting of five executive function tests will be administered at each time point.