Longitudinal Tracking of Traumatic Brain Injury: Advanced Connectomics

创伤性脑损伤的纵向追踪：高级连接组学

• 批准号: 9259811
• 负责人: Emily Larsen Dennis
• 金额: $ 8.78万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9259811
• 关键词: Acute; Adolescent; Adult; Affect; Afghanistan; Age; Animals; Anterior; Area; Atlases; Biochemistry; Biological; Biological Markers; Blast Cell; Brain; Brain Injuries; Brain Mapping; Brain imaging; Cause of Death; Child; Childhood; Childhood Injury; Chronic Phase; Clinical; Collaborations; Corpus Callosum; Craniocerebral Trauma; Data; Data Analyses; Data Set; Demyelinations; Development; Developmental Process; Diffusion; Diffusion Magnetic Resonance Imaging; Electroencephalography; Emergency department visit; Environment; Event; Fiber; Foundations; Goals; Heterogeneity; Hockey; Image; Incidence; Individual; Inflammation; Injury; Institutes; Intake; Interruption; Iraq; Knowledge; Length; Longitudinal Studies; Longitudinal cohort; Magnetic Resonance Spectroscopy; Manufactured football; Maps; Measures; Mental disorders; Mentors; Meta-Analysis; Methods; Military Personnel; Modality; Moscow; Neurobiology; Neuropsychology; Outcome; Participant; Pathway interactions; Patients; Pattern; Play; Population; Process; Public Health; Recovery; Reporting; Resolution; Resources; Risk; Russia; Sampling; Scientist; Seasons; Site; Source; Spectrum Analysis; Sports; Time; Training; Translating; Traumatic Brain Injury; United States; Veterans; Work; aged; base; career; clinical research site; cognitive testing; cohort; college; combat; disability; follow-up; high risk; high school; imaging modality; imaging study; improved; indexing; inflammatory marker; longitudinal analysis; myelination; nervous system disorder; neurochemistry; neuron loss; outcome prediction; patient population; prevent; prognostic tool; public health relevance; relating to nervous system; service member; targeted treatment; trend; white matter; white matter damage

 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.

 描述（由申请人提供）：我的项目应用先进的多模式连接组学方法来研究创伤性脑损伤（TBI）如何纵向影响大脑，跨越几个队列。我分析了TBI风险较高的三个人群：儿童和青少年，运动员和军人。TBI与发展神经和精神疾病的风险较高有关，在儿童和青少年中，它可以延迟或破坏正在进行的大脑发育。有相当大的异质性损伤后的结果，这是很难解释现有的预后工具。来自我们开发的先进连接组学方法的生物标志物，包括利用功能，结构和神经化学信息的多模态数据，将提高我们对TBI中白色物质（WM）损伤和预测结果的敏感性。很少有TBI的纵向研究，特别是大样本和损伤后有限的评估间隔。由于存在损伤后神经生物学事件的动态级联，因此受限的损伤后窗口至关重要。在我的建议中，我纵向跟踪了3个队列，以研究TBI如何改变大脑连接，它如何恢复，以及哪些因素影响恢复过程。基于这个目标，我有四个目标：（1）使用我们实验室开发的新方法autoMATE来识别与TBI相关的基于束的白色物质完整性指数的中断（自动多图谱道提取）;（2）使用我们实验室开发的另一种方法EPIC识别与TBI相关的网络连接改变（发展分区以改善连接组学）;（3）将来自DWI和磁共振波谱（MRS）的联合收割机数据结合起来，以了解TBI中的炎症和WM破坏;（4）扩展这些分析，以包括来自世界各地合作者的其他队列。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（损伤后1-5个月）和慢性期（损伤后13-19个月），通过脑成像和认知评估对其进行评估。第二批是现役美国服务人员，他们在伊拉克或阿富汗期间持续TBI，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，并进行大脑成像和认知评估。第三种是UCLA校队运动员，他们从事NCAA认可的接触性运动，年龄在17-23岁之间。他们在赛季初进行评估，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，将用于横截面和纵向分析。将MRS的神经化学谱与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，尊重临床和研究中心的异质性。确定哪些生物标志物和结果是可复制和可推广的，对于将其转化为生物标志物和结果至关重要。 更多的患者群体。我的纵向多式联运项目将促进我们对TBI后恢复的理解。