Traumatic and Treatable Vascular Pathology in the Outcome of TBI

Objective: The overarching objective of this career development proposal is to develop Dr. Swanson’s translational approach for investigating the relationship between mild traumatic brain injury (mTBI) exposure(s), modifiable cardiovascular risk factors, and non-invasive measures of chronic cerebral microvascular pathology, including advanced neuroimaging modalities. Research Design and Methodology: Through resource sharing, previously collected and archived clinical data, neuroimaging data, and blood samples from the joint DoD/VA Long-Term Impact of Military-Relevant Brain Injury Consortium – Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) Prospective Longitudinal Study Cohort will be utilized to perform a retrospective cohort study. Aim-I will investigate potential associations between mTBI exposure(s) and advanced neuroimaging measures of chronic cerebral microvascular pathology. Primary analysis will explore associations between the number of mTBI exposures (none, 1-2, or 3+) and two independent advanced neuroimaging measures of cerebral microvascular pathology (white matter hyperintensity quantification with Brain Intensity Abnormality Classification Algorithm [BIANCA] analysis, and diffusion-MRI Free Water Volume Fraction [FW-VF] analysis) at a single point in time (initial neuroimaging acquisition upon entry into the LIMBIC-CENC study), adjusting for both age and sex. Secondary analysis will further categorize the mTBI exposure history into 7 severity subgroups (accounting for the presence or absence of associated post-traumatic amnesia and loss of consciousness), and then explore associations between resulting mTBI exposure severity and BIANCA / FW- VF advanced neuroimaging analysis, adjusting for age and sex. Aim-II will investigate potential associations between modifiable cardiovascular risk factors and advanced neuroimaging measures of chronic cerebral microvascular pathology. Using a combination of ideal cardiovascular health (I-CVH) behaviors (physical activity, sleep duration, smoking and alcohol use) and factors (body mass index, blood pressure, total cholesterol, and diabetes mellitus status), we will calculate patient-specific I-CVH Index scores and explore associations with BIANCA / FW-VF neuroimaging measures of cerebral microvascular pathology, adjusting for age, sex and mTBI exposure(s) as independent risk factors. In addition, we will evaluate longitudinal changes in cerebral microvascular pathology at 1, 3 & 5-year follow-up. Candidate, Career Goals, Research Career Development: Dr. Randel Swanson is a prior enlisted U.S. Marine who is board-certified in Physical Medicine & Rehabilitation, with subspecialty board certification in Brain Injury Medicine. He is an Assistant Professor of Physical Medicine & Rehabilitation at the University of Pennsylvania, and an Attending Physician at the Corporal Michael J. Crescenz VA Medical Center, where he serves as a Polytrauma/TBI System of Care team physician. Dr. Swanson’s immediate career goals are to acquire the necessary technical knowledge and leadership skills to coordinate a multidisciplinary translational research team focused on investigating cerebral microvascular pathology in TBI and cardiovascular disease, with the long-term career goal of sustaining a translational research career within the VA Healthcare System. To achieve these goals, Dr. Swanson has put together an expert mentorship team, and will receive advanced training through Penn’s Institute for Translational Medicine and Therapeutics. At the end of the CDA2 period, it is expected that Dr. Swanson will have established a robust VA-based translational TBI laboratory.