Traumatic and Treatable Vascular Pathology in the Outcome of TBI

目标：本职业发展计划的首要目标是发展斯旺森博士的 研究轻度创伤性脑损伤（mTBI）暴露与脑损伤之间关系的转化方法， 可改变的心血管危险因素，以及慢性脑微血管病理学的非侵入性测量， 包括先进的神经成像设备 研究设计和方法：通过资源共享，以前收集和存档的临床 数据、神经影像学数据和血液样本来自国防部/退伍军人管理局联合的军事相关长期影响研究。 脑损伤联盟-神经创伤联盟慢性效应（LIMBIC-CENC）前瞻性 将使用纵向研究队列进行回顾性队列研究。 目标-I将研究mTBI暴露与高级神经影像学指标之间的潜在关联 慢性脑微血管病变主要分析将探讨 mTBI暴露（无、1 - 2或3+）和两项独立的高级脑神经影像学指标 微血管病理学（白色高信号定量，脑强度异常 分类算法[BIANCA]分析和扩散-MRI游离水体积分数[FW-VF]分析） 在单个时间点（进入LIMBIC-CENC研究后的初始神经成像采集），调整 年龄和性别。次要分析将进一步将mTBI暴露史分为7种严重程度 亚组（考虑是否存在相关的创伤后遗忘症和丧失的 意识），然后探索导致的mTBI暴露严重程度和BIANCA/FW之间的关联- VF高级神经成像分析，根据年龄和性别进行调整。 Aim-II将研究可改变的心血管危险因素与晚期 慢性脑微血管病变的神经影像学测量。使用理想的 心血管健康（I-CVH）行为（体力活动、睡眠时间、吸烟和饮酒）， 因素（体重指数，血压，总胆固醇和糖尿病状态），我们将计算 患者特异性I-CVH指数评分，并探索与BIANCA/FW-VF神经影像学指标的相关性， 脑微血管病理学，调整年龄，性别和mTBI暴露作为独立的风险因素。在 此外，我们将在1年、3年和5年的随访中评估脑微血管病理学的纵向变化。 候选人，职业目标，研究职业发展：兰德尔斯旺森博士是一个先前入伍的美国。 海洋谁是董事会认证的物理医学和康复，与子专业委员会认证， 脑损伤医学他是纽约大学物理医学与康复助理教授， 宾夕法尼亚州，并在下士迈克尔J. Crescenz VA医疗中心，在那里他的主治医生， 担任多创伤/TBI护理系统团队医生。斯旺森博士的近期职业目标是 获得必要的技术知识和领导技能，以协调多学科翻译 研究小组专注于研究TBI和心血管疾病中的脑微血管病理学， 长期的职业目标是在VA医疗保健系统内维持翻译研究事业。 为了实现这些目标，斯旺森博士组建了一个专家指导团队，并将获得先进的 通过宾夕法尼亚大学转化医学和治疗研究所进行培训。在CDA2周期结束时， 预计Swanson博士将建立一个强大的基于VA的翻译TBI实验室。

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.