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

项目摘要 儿科心脏骤停很常见，因此发病率和死亡率都很高。神经性残疾 发生在高达80%的心脏骤停幸存的儿童身上。心脏骤停后的脑损伤是由 最初的缺氧-缺血事件和随后几小时至几天内发生的继发性脑损伤。这个 减少继发性脑损伤是心脏骤停后护理的重点。脑自动调节(CAR)是 脑血管扩张或收缩以维持大脑相对恒定的生理过程 平均动脉压(MAP)范围内的血流量(CBF)。受损的汽车会让大脑 易受低灌流和高灌流状态的影响，这可能导致继发性脑损伤和 可预防的神经性残疾。关于哪一辆车最完整的地图，知识上存在差距 儿童心脏骤停后，偏离这一最优MAP对脑损伤和临床的影响 结果。这项建议的中心假设是，患者的MAP差异较大 心脏骤停后最佳的MAP会造成更严重的脑微结构损伤和临床结局。 在这项建议中，将使用先进的非侵入性光学成像直接测量CBF 这项技术被称为漫相关光谱(DCS)，将被用来计算最优MAP。脑区 损伤将使用扩散磁共振成像(MRI)进行量化。主要的临床结果是 根据儿科脑功能分类，出院时的神经功能障碍。这个 拟议研究的目标是确定与他们的DC有较大偏差的患者是否- 确定的最优MAP具有较差的临床结果(目标1)和弥漫性脑微结构损伤 MRI(AIM 2)与偏离最佳MAP较小的患者进行比较。此外，地区性CBF 来自动脉自旋标记(ASL)MRI(AIM 3)的脑血流量将与源自DCS的CBF相关。 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告知未来脑生理学靶向治疗策略的试验 以改善儿科心脏骤停的预后。申请者Matthew Kirschen医生是一名儿科重症医生， 费城儿童医院和宾夕法尼亚大学的神经科医生将从事一项严格的 儿童心脏骤停、脑生理学教学课程及专家辅导的培训方案 以及自动调节和大脑成像。他将通过临床生物统计学硕士获得专业知识 临床流行病学科学计划、先进的光学成像和扩散磁共振成像分析。通过 建议的学习，他的平行职业发展计划，一个敬业而有经验的导师团队，以及 世界一流的环境，Kirschen医生将实现成为独立的神经危重护理人员的目标 研究科学家，特别关注儿童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.