Longitudinal Tracking of Traumatic Brain Injury: Advanced Connectomics

 描述(由申请者提供)：我的项目应用先进的多模式连接学方法来研究创伤性脑损伤(TBI)如何在几个队列中纵向影响大脑。我分析了三个脑外伤高危人群：儿童和青少年、运动员和军人。脑外伤与患神经和精神疾病的风险较高有关，在儿童和青少年中，它可能会延迟或扰乱正在进行的大脑发育。损伤后的预后有相当大的异质性，现有的预后工具很难解释这一点。我们开发的先进连接组学方法的生物标记物，包括利用功能、结构和神经化学信息的多模式数据，将提高我们在绘制脑损伤白质(WM)损伤和预测结果方面的敏感性。很少有关于颅脑损伤的纵向研究，尤其是大样本和有限的损伤后评估间隔。由于存在损伤后神经生物学事件的动态级联，因此有限的损伤后窗口是至关重要的。在我的建议中，我纵向跟踪了3个队列，以检查脑损伤如何改变大脑连接，它是如何恢复的，以及哪些因素影响恢复过程。有了这个目标，我有四个目标：(1)使用我们实验室开发的新方法Automate(自动多图谱脑束提取)识别与脑损伤相关的白质完整性指标的中断；(2)使用我们实验室开发的另一种方法EPIC(改进连接的分区进化)识别与脑损伤相关的网络连接改变；(3)结合DWI和磁共振波谱(MRS)的数据来了解脑损伤的炎症和西医破坏；(4)扩展这些分析，以包括来自世界各地的合作者的更多队列。我的第一个队列是儿科队列(RAPBI)，包括8-19岁的儿童和青少年。在急性期(伤后1-5个月)和慢性期(伤后13-19个月)用脑成像和认知评估对他们进行评估。第二组是现役美国军人，他们在伊拉克或阿富汗期间患有创伤性脑损伤，年龄在18-60岁之间。他们在摄入后6个月内的4个时间点进行评估，并进行脑部成像和认知评估。第三类是加州大学洛杉矶分校的校队运动员，他们参加NCAA认可的接触式运动，年龄在17-23岁之间。他们在赛季开始时接受评估，在受伤后接受6次后续成像和认知评估。Automate和EPIC是先进的方法，具有更高的检测变化的灵敏度，将用于横断面和纵向分析。将MRS的神经化学光谱与DWI的扩散信息相结合，将有助于我们通过揭示潜在生物化学的破坏来解释结果。通过荟萃分析，我将检查跨队列趋势，尊重临床和部位的异质性。确定哪些生物标志物和结果是可复制和可推广的，这对于将它们转化为 更多的病人。我的纵向多模式项目将促进我们对脑外伤后恢复的理解。

 DESCRIPTION (provided by applicant): My project applies advanced, multi-modal connectomics methods to study how traumatic brain injury (TBI) affects the brain longitudinally, across several cohorts. I analyze three populations at heightened risk of TBI: children and adolescents, athletes, and military service members. TBI is associated with higher risk of developing neurological and psychiatric disorders, and in children and adolescents it can delay or disrupt ongoing brain development. There is considerable heterogeneity in post-injury outcome, which is poorly explained by existing prognostic tools. Biomarkers from advanced connectomics methods that we have developed, including multi-modal data harnessing functional, structural, and neurochemical information will improve our sensitivity for mapping white matter (WM) damage in TBI and predicting outcome. There are few longitudinal studies of TBI, especially with large samples and circumscribed assessment intervals post-injury. As there is a dynamic cascade of post-injury neurobiological events, a restricted post-injury window is critical. In my proposal, I follow 3 cohorts longitudinally to examine how brain connectivity is altered by TBI, how it recovers, and what factors impact the recovery process. With this goal, I have four aims: (1) identify disruptions in tract-based indices of white matter integrity associate with TBI using a new method developed by our lab, autoMATE (automated multi-atlas tract extraction); (2) identify network connectivity alterations associated with TBI using another method developed by our lab, EPIC (evolving partitions to improve connectomics); (3) combine data from DWI and magnetic resonance spectroscopy (MRS) to understand inflammation and WM disruption in TBI; (4) expand these analyses to include additional cohorts from collaborators across the world. My first cohort is a pediatric cohort (RAPBI), including children and adolescents aged 8-19 years. They are assessed in the post-acute (1-5 months post-injury) and chronic phases (13-19 months post-injury) with both brain imaging and cognitive assessments. The second cohort is active duty U.S. Service Members who sustained TBI while in Iraq or Afghanistan, between 18-60 years old. They are assessed at 4 time-points within 6 months of intake, with brain imaging and cognitive assessments. The third is UCLA varsity athletes who play an NCAA-recognized contact sport, between 17-23 years old. They are assessed at the beginning of the season, and after an injury receive 6 follow-up imaging and cognitive assessments. AutoMATE and EPIC are advanced methods, with increased sensitivity for detecting change, and will be used for both cross-sectional and longitudinal analyses. Integrating neurochemical spectra from MRS with the diffusion information from DWI will help us interpret results by revealing disruptions in underlying biochemistry. Through meta-analyses, I will examine cross-cohort trends, respecting the clinical and site heterogeneity. Determining what biomarkers and results are replicable and generalizable is critical to translating them to the greater patient population. My longitudinal multi-modal project will advance our understanding of recovery post-TBI.