Cerebral autoregulation and MRI measures of brain injury after pediatric-post cardiac arrest

项目摘要 小儿心脏骤停是常见的，导致高发病率和死亡率。神经功能失能 在心脏骤停后存活的儿童中发生率高达80%心脏骤停后的脑损伤是由 最初的缺氧缺血事件和随后数小时至数天内发生的继发性脑损伤。的 心脏骤停后护理的重点是减少继发性脑损伤。大脑自动调节（CAR）是一种 脑血管扩张或收缩以维持大脑相对稳定的生理过程 在平均动脉血压（MAP）范围内的血流量（CBF）。受损的CAR使大脑 易受低灌注和高灌注状态的影响，这可能导致继发性脑损伤， 可预防的神经功能障碍关于CAR最完整的MAP存在知识缺口 儿童心脏骤停后，以及偏离此最佳MAP对脑损伤和临床的影响 结果。该建议的中心假设是，MAP差异较大的患者 心脏骤停后最佳MAP会导致更严重的脑微结构损伤和临床结局。 对于这项建议，CBF将直接使用先进的，非侵入性的光学成像测量 技术称为扩散相关光谱（DCS），这将用于计算最佳MAP。大脑 将使用扩散磁共振成像（MRI）来量化损伤。主要临床结局是 出院时基于小儿脑功能分类的神经功能残疾。的 拟议研究的目的是确定与DCS有较大偏差的患者- 确定的最佳MAP具有较差的临床结局（目标1）和弥散性微结构脑损伤 MRI（目标2）与最佳MAP偏差较小的患者相比。此外，区域CBF 从DCS导出的CBF将与从动脉自旋标记（ASL）MRI导出的CBF相关（目的3）。 这些研究的成功完成将进一步加深我们对潜在机制的理解 心脏骤停后脑损伤，并为未来的脑生理学靶向管理策略试验提供信息 来改善小儿心脏骤停的预后。申请人Matthew Kirschen博士是一名儿科重症监护医生， 费城儿童医院和宾夕法尼亚大学的神经学家将进行严格的 由儿科心脏骤停、脑生理学专家讲授课程和指导的培训方案 自动调节和脑成像。他将通过硕士学位获得临床生物统计学方面的专业知识。 临床流行病学科学计划，先进的光学成像和扩散MRI分析。通过 建议的研究，他的平行职业发展计划，一个专门和经验丰富的导师团队，以及一个 在世界一流的环境中，Kirschen博士将实现成为独立的神经重症监护医生的目标。 研究科学家，特别关注小儿心脏骤停后的神经复苏。

PROJECT ABSTRACT Pediatric cardiac arrest is common, with resultant high morbidity and mortality. Neurologic disability occurs in up to 80% of children who survive a cardiac arrest. Brain injury after cardiac arrest is caused by the initial hypoxic-ischemic event and from secondary brain injury that occurs in the following hours to days. The focus of post-cardiac arrest care is to reduce secondary brain injury. Cerebral autoregulation (CAR) is a physiologic process by which cerebral blood vessels dilate or constrict to maintain relatively constant cerebral blood flow (CBF) across a range of mean arterial blood pressures (MAPs). Impaired CAR makes the brain vulnerable to states of hypoperfusion and hyperperfusion which can contribute to secondary brain injury and preventable neurologic disability. There is a knowledge gap regarding the MAP at which CAR is most intact after pediatric cardiac arrest, and the impact of the deviation from this optimal MAP on brain injury and clinical outcomes. The central hypothesis of this proposal is that patients with larger differences between their MAP and optimal MAP after cardiac arrest will have worse microstructural brain injury and clinical outcomes. For this proposal, CBF will be measured directly using an advanced, non-invasive optical imaging technique called diffuse correlation spectroscopy (DCS), which will be used to calculate optimal MAP. Brain injury will be quantified using diffusion magnetic resonance imaging (MRI). The primary clinical outcome is neurologic disability at hospital discharge based on the Pediatric Cerebral Performance Category. The objectives of the proposed research are to determine whether patients with larger deviations from their DCS- determined optimal MAP have worse clinical outcomes (Aim 1) and microstructural brain injury on diffusion MRI (Aim 2) compared to patients with smaller deviations from their optimal MAP. In addition, regional CBF derived from DCS will be correlated with CBF derived from arterial spin labeled (ASL) MRI (Aim 3). The successful completion of these studies will further our understanding of the mechanisms underlying post-cardiac arrest brain injury and inform future trials of cerebral physiology-targeted management strategies to improve pediatric cardiac arrest outcomes. The applicant, Dr. Matthew Kirschen, a pediatric intensivist and neurologist at the Children’s Hospital of Philadelphia and University of Pennsylvania, will engage in a rigorous training program of didactic courses and mentoring by experts in pediatric cardiac arrest, cerebral physiology and autoregulation, and brain imaging. He will gain expertise in clinical biostatistics through the Master of Science in Clinical Epidemiology program, advanced optical imaging, and diffusion MRI analytics. Through the proposed studies, his parallel career development plan, a team of dedicated and experienced mentors, and a world-class environment, Dr. Kirschen will achieve his goal of becoming an independent neurocritical care research scientist with special focus on neurologic resuscitation following pediatric cardiac arrest.