Traumatic and Treatable Vascular Pathology in the Outcome of TBI

目标：这份职业发展提案的首要目标是发展斯旺森博士的 轻型创伤性脑损伤暴露与关系的翻译研究(S)， 可改变的心血管危险因素，以及慢性脑微血管病变的非侵入性措施， 包括先进的神经成像设备。 研究设计和方法：通过资源共享，收集和存档先前的临床资料 数据、神经成像数据和联合国防部/退伍军人事务部血液样本对军事的长期影响 脑损伤联盟-神经损伤联盟的慢性影响(边缘-CENC)前瞻性 将利用纵向研究队列进行回溯性队列研究。 AIM-I将研究mTBI暴露(S)与高级神经成像措施之间的潜在关联 慢性脑微血管病变。初步分析将探索以下数量之间的关联 MTBI暴露(无、1-2或3+)和两种独立的高级脑部成像测量 微血管病理学(脑白质高信号定量与脑强度异常 分类算法[Bianca]分析和扩散-磁共振自由水体积分数[FW-VF]分析) 在单个时间点(进入Limbic-CENC研究时的初始神经成像采集)，调整 年龄和性别都是。二次分析将mTBI暴露史进一步分类为7种严重程度 亚组(说明有或没有相关的创伤后遗忘症和丧失 意识)，然后探索由此产生的mTBI暴露严重程度与Bianca/FW- VF高级神经成像分析，根据年龄和性别进行调整。 AIM-II将调查可改变的心血管危险因素和晚期心血管疾病之间的潜在联系 慢性脑微血管病变的神经影像检查方法。使用理想的组合 心血管健康(I-CVH)行为(体力活动、睡眠时间、吸烟和饮酒)和 因素(体重指数、血压、总胆固醇和糖尿病状况)，我们将计算 患者特定的I-CVH指数评分，并探讨与Bianca/FW-VF神经成像指标的相关性 脑微血管病理，调整了年龄、性别和mTBI暴露(S)为独立危险因素。在……里面 此外，我们将在1、3和5年的随访中评估脑微血管病理的纵向变化。 候选人，职业目标，研究职业发展：兰德尔·斯旺森博士是一名曾入伍的美国 海军陆战队，在物理医学和康复方面拥有董事会认证，并拥有 脑损伤医学。他是加州大学物理医学与康复学助理教授。 宾夕法尼亚州，下士迈克尔·J·克雷森兹退伍军人医学中心的主治医生，在那里他 担任多处创伤/创伤性脑损伤护理团队医生。斯旺森博士近期的职业目标是 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脑外伤和心血管疾病的脑微血管病理， 长期的职业目标是在退伍军人管理局医疗系统内维持翻译研究的职业生涯。 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学研究所进行培训。在CDA2时期结束时，它 预计斯旺森博士将建立一个强大的以退伍军人事务部为基础的转化性脑损伤实验室。

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.