Cerebral Perfusion and Cognitive Outcomes in Mild Traumatic Brain Injury

项目摘要/摘要 据估计，从最近的伊拉克战争中返回的美国军人中，大约有20% 和阿富汗在部署期间至少有一人头部受伤。在这些伤害中，近83%可以 被归类为轻度，是钝力(即直接打击头部)或与爆炸有关的直接结果 (即简易爆炸装置的高压)创伤。虽然短期和长期 神经创伤的后果现在才开始被意识到，那些有轻微创伤病史的人 脑损伤(MTBI)表现为残疾和精神障碍的发生率增加，生活质量下降， 严重的认知缺陷，以及脑震荡后症状(PCS)的麻烦经历，与 无脑外伤病史者。尽管研究很少，但脑血管功能障碍在 MTBI后的结果最近开始受到越来越多的关注。重要的是，大脑依赖于 稳定的脑血流(CBF)执行一系列功能过程并保持神经元的完整性。 脑血流(CBF)的短暂波动和/或长期变化与负值有关 病理后果(例如，神经变性、缺血)和认知功能障碍。在上下文中 对于mTBI，生物力学和动物模型表明，血管或脑的初级结构变化 由次级细胞和/或分子启动的微血管提供的实质 神经炎性级联反应可显著改变损伤后的脑血流量。因此，迫切需要 了解和澄清CBF改变的性质及其对负面健康的潜在贡献 MTBI的结果，特别是在慢性期。因此，当前的提案寻求使用最先进的技术， 无创、多时相伪连续动脉自旋标记(MPPCASL)神经成像方法：(1) 评估有脑挫伤病史的患者脑血流量是否发生变化；(2)探讨脑血流量与脑血流量的关系 静息脑血流量和神经心理功能；以及(3)在探索性分析中，检查可能的调节因素 和/或有脑外伤病史的静息脑血流量和认知功能的调节因子。重要的是，理解 CBF的性质和对mTBI患者不良结局的潜在贡献将有助于预防 以及目前正在开发的干预策略，以减轻对 那些遭受头部创伤的人。具体地说，从这项提案中收集的信息有可能 以改善诊断，帮助症状管理，并可能提供两者的有用生物标记物 持续存在神经和行为功能障碍的脆弱人群的损害和康复 人们对此仍然知之甚少。

PROJECT SUMMARY/ABSTRACT It has been estimated that approximately 20% of U.S. service members returning from the recent wars in Iraq and Afghanistan have suffered at least one head injury during deployment. Nearly 83% of these injuries can be classified as mild and are the direct result of either blunt-force (i.e., direct blow to the head) or blast-related (i.e., high pressure from an improvised explosive device) trauma. Though the short and long-term consequences of neurotrauma are now only beginning to be appreciated, those with history of mild traumatic brain injury (mTBI) show increased rates of disability and psychiatric disorders, decreased quality of life, significant cognitive deficits, and troublesome experience of post-concussive symptoms (PCS), relative to those with no history of mTBI. Though vastly understudied, the role of the cerebrovascular dysfunction in outcomes after mTBI has recently begun to garner increasing attention. Importantly, the brain is reliant on steady cerebral blood flow (CBF) to carry out a host of functional processes and maintain neuronal integrity. Brief fluctuations and/or prolonged alterations in cerebral blood flow (CBF) have been linked to negative pathological consequences (e.g., neurodegeneration, ischemia) and cognitive dysfunction. Within the context of mTBI, biomechanical and animal models suggest that primary structural alterations to vasculature or brain parenchyma supplied by microvasculature coupled with secondary cellular and/or molecular initiated neuroinflammatory cascades could greatly alter CBF post-injury. Therefore, there is a critical need to understand and clarify the nature of CBF alterations and its potential contributions to negative health outcomes in mTBI, particularly in chronic stages. The current proposal therefore seeks to use state-of-the art, non-invasive, multi-phase pseudo-continuous arterial spin labeling (MPPCASL) neuroimaging methods to:  (1) evaluate whether CBF changes occur in those with history of mTBI; (2) investigate the relationship between resting CBF and neuropsychological function; and (3) in exploratory analyses, examine possible mediators and/or moderators of resting CBF and cognition in those with history of mTBI. Importantly, understanding the nature and underlying contribution of CBF to poor outcomes in those with mTBI will help inform prevention and interventional strategies that are currently being developed to mitigate negative health consequences for those who have sustained head trauma. Specifically, information gleaned from this proposal has the potential to improve diagnosis, aid in symptom management, and possibly provide a useful biomarker of both impairment and recovery in a vulnerable population where persistent neurological and behavioral dysfunction remains poorly understood.