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.

Public Health Relevance

Traumatic brain injury (TBI) is the cause of 2.5 emergency room visits annually in the U.S., making it a major public health issue and a source of enormous financial burden. While TBI largely occurs through random events, particular groups have an increased risk of TBI, including children, military service members, and athletes, and TBI can be especially damaging to the still maturing brains of children and adolescents. My proposal applies advanced connectomics and multi-modal analyses longitudinally across several cohorts, providing the foundation for a TBI imaging consortium as we expand our analyses to new groups.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Career Transition Award (K99)
Project #
5K99NS096116-02
Application #
9259811
Study Section
NST-2 Subcommittee (NST-2)
Program Officer
Bellgowan, Patrick S F
Project Start
2016-04-15
Project End
2018-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
2
Fiscal Year
2017
Total Cost
$87,750
Indirect Cost
$6,500
Name
University of Southern California
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
Dennis, Emily L; Rashid, Faisal; Faskowitz, Josh et al. (2017) MAPPING AGE EFFECTS ALONG FIBER TRACTS IN YOUNG ADULTS. Proc IEEE Int Symp Biomed Imaging 2017:101-104
Dennis, Emily L; Rashid, Faisal; Jahanshad, Neda et al. (2017) A NETWORK APPROACH TO EXAMINING INJURY SEVERITY IN PEDIATRIC TBI. Proc IEEE Int Symp Biomed Imaging 2017:105-108
Dennis, Emily L; Faskowitz, Joshua; Rashid, Faisal et al. (2017) Diverging volumetric trajectories following pediatric traumatic brain injury. Neuroimage Clin 15:125-135
Dennis, Emily L; Hua, Xue; Villalon-Reina, Julio et al. (2016) Tensor-Based Morphometry Reveals Volumetric Deficits in Moderate=Severe Pediatric Traumatic Brain Injury. J Neurotrauma 33:840-52
Dennis, Emily L; Rashid, Faisal; Villalon-Reina, Julio et al. (2016) Multi-modal Registration Improves Group Discrimination in Pediatric Traumatic Brain Injury. Brainlesion (2016) 10154:32-42
Dennis, Emily L; Ellis, Monica U; Marion, Sarah D et al. (2015) Callosal Function in Pediatric Traumatic Brain Injury Linked to Disrupted White Matter Integrity. J Neurosci 35:10202-11