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

基本信息

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
项目类别：
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

项目摘要

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，在几个队列中我分析了三个完全有 TBI 风险的人群：儿童和青少年、运动员。创伤性脑损伤与发生神经和精神疾病的较高风险有关，并且在儿童和青少年中，它可能会延迟或破坏正在进行的大脑发育。损伤后的结果存在相当大的异质性，这一点很难解释。通过我们开发的先进连接组学方法的现有预后工具，包括利用功能、结构和神经化学信息的多模式数据，将提高我们绘制 TBI 中白质 (WM) 损伤和预测结果的敏感性。 TBI 的研究，尤其是大样本和有限的损伤后评估间隔，由于损伤后神经生物学事件存在动态级联，因此限制损伤后窗口至关重要，在我的建议中，我遵循 3。为了实现这一目标，我有四个目标：（1）确定与 TBI 相关的基于束的白质完整性指数的破坏。使用我们实验室开发的新方法 autoMATE（自动多图集束提取）；（2）使用我们实验室开发的另一种方法 EPIC（进化分区以改善连接组学）识别与 TBI 相关的网络连接改变；来自 DWI 和磁共振波谱 (MRS) 的数据，以了解 TBI 中的炎症和 WM 破坏；(4) 扩展这些分析，以纳入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)，包括儿童和青少年。他们在急性期（受伤后 1-5 个月）和慢性期（受伤后 13-19 个月）接受脑成像和认知评估。在伊拉克或阿富汗期间遭受 TBI 的美国现役军人，年龄在 18-60 岁之间，他们在入伍后 6 个月内的 4 个时间点接受脑成像和认知评估。 NCAA 认可的接触性运动，年龄在 17-23 岁之间，他们在赛季开始时接受评估，并在受伤后接受 6 次后续影像和认知评估，AutoMATE 和 EPIC 是先进的方法。提高检测变化的灵敏度，并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，将有助于我们通过荟萃分析揭示潜在生物化学的破坏来解释结果。检查跨队列趋势，尊重临床和位点异质性，确定哪些生物标志物和结果是可复制和可推广的，这对于将其转化为结果至关重要。我的纵向多模式项目将增进我们对 TBI 后康复的理解。