A Longitudinal Multi-modal Neuroimaging Investigation of Functional Recovery afte

描述（由申请人提供）：创伤性脑损伤（TBI）是年轻人长期残疾的主要原因，这一事实强调了将应对TBI概念化为终身恢复和康复过程的必要性。在不断发展的恢复过程中，神经病理学标志物的成功表征将成为开发更有效的诊断和干预的重要一步。虽然已经确定行为结果测量在受伤后的几个月甚至几年内显示出显着的改善，但这种恢复的潜在神经机制尚未得到很好的理解。随着体内神经影像学的最新进展，现在可以更准确地测量初始损伤病理学，并阐明纵向设计中自然恢复过程的机制。然而，图像分析的挑战阻碍了TBI研究人员充分利用新的成像模式。TBI神经影像学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）将异质性大脑登记到共同空间中，以及3）评估结构-功能关系（例如，神经机能不能）。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对照和TBI之间显示结构和官能团差异的区域。基于这些初步工作，当前项目的目标是：1）确定与中度至重度弥漫性轴索损伤相关的结构和功能神经影像学指标的纵向变化模式及其与行为改善的关系，2）使用急性后早期的纵向变化开发基于神经病理学的损伤严重程度测量，以及3）开发“结构-功能差异”指数，根据损伤后不同时间点获得的结构和功能完整性影像学测量值的差异，并收集其与行为恢复关系的初步数据.我们建议评估60例中重度弥漫性TBI患者在急性期后的结构（总体积变化和白色物质完整性）和功能（脑灌注和功能连接）神经影像学指标在多个时间点（损伤后3、6和12个月）。出于比较目的，将对36例人口统计学匹配的健康对照受试者进行评价。为了测量行为的纵向改善，将在每个时间点进行总体行为结局测量和由五项执行功能测试组成的神经心理学测试组合。

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.