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

小儿心脏骤停后脑损伤的大脑自动调节和 MRI 测量

• 批准号: 10667613
• 负责人: Matthew P Kirschen
• 金额: $ 20.37万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667613
• 关键词: Acute Brain Injuries; Affect; Age; Anisotropy; Bilateral; Biometry; Blood Pressure; Brain; Brain Hypoxia-Ischemia; Brain Injuries; Brain imaging; Cardiac; Caring; Categories; Cerebrovascular Circulation; Cerebrovascular system; Cerebrum; Characteristics; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Critical Care; Data; Dedications; Development Plans; Diffuse; Diffuse Brain Injury; Diffusion; Diffusion Magnetic Resonance Imaging; Doctor of Philosophy; Environment; Event; Fellowship; Future; Goals; Heart Arrest; Homeostasis; Hospitals; Hour; Imaging Techniques; Impairment; Intervention Trial; Knowledge; Left; Magnetic Resonance Imaging; Master of Science; Measures; Mediating; Mediation; Mentors; Metabolic; Methods; Monitor; Morbidity - disease rate; Near-Infrared Spectroscopy; Nervous System Trauma; Neurologic; Neurologist; Neurology; Neurosciences; Optical Methods; Outcome; Patients; Pediatric Hospitals; Pediatric cohort; Pennsylvania; Performance; Philadelphia; Physiological Processes; Physiology; Qualifying; Radial; Recommendation; Research; Resuscitation; Scientist; Secondary to; Severities; Spectrum Analysis; Testing; Time; Training; Training Programs; Translating; Universities; age related; arterial spin labeling; blood pressure control; career; career development; cerebral hypoperfusion; clinical epidemiology; clinical practice; constriction; disability; epidemiology study; experience; frontal lobe; hypoperfusion; hypoxic ischemic injury; improved; improved outcome; individual patient; mortality; non-invasive optical imaging; optical imaging; pediatric patients; pressure; prevent; primary outcome; programs; skills; white matter

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.

项目摘要 儿科心脏骤停是常见的，导致了高病态和神经疾病的死亡率 在心脏骤停后幸存的儿童中，多达80％的发生。 在接下来的几个小时到几天中，最初的缺氧性事件和继发性脑损伤发生 心脏骤停的重点是减少脑损伤。 大脑血管扩张或收缩到脑相对大脑的生理过程 横跨一系列平均动脉血压（地图）的血流（CBF）。 容易受到灌注不良和灌注过度灌注状态的影响，这可能导致次要脑损伤和 可预防的神经性残疾。 小儿心脏骤停后，以及偏离最佳地图对脑损伤和临床的影响 结果。 心脏骤停后的最佳图将带来微观结构的脑损伤和临床结果。 对于此提案，使用高级的非侵入性光学成像直接测量的CBF 技术称为弥漫性相关性特殊镜（DC），该技术将用于计算最佳图。 损伤将使用扩散磁共振成像（MRI）进行定量。 医院的神经疾病在小儿大脑表现类别中低音 支撑研究的目标是确定偏离较大偏离DCS-的患者是否是否存在 确定的最佳图具有W家庭临床结果（AIM 1）和扩散时的微结构脑损伤 MRI（AIM 2）与最佳地图较小的患者相比。 从DC衍生的将与源自标记（ASL）MRI的动脉自旋（AIM 3）的CBF相关。 这些石块的成功完成将掩盖基本机制 心脏骤停后脑损伤并为未来​​的CereSiology-pargenting管理策略脑脑损伤提供了未来的试验 改善儿科心脏骤停结果。 费城儿童医院和宾夕法尼亚大学的神经科医生将进行严格 小儿心脏骤停专家的教学课程和指导的培训计划，脑生理学 和自动调节和大脑成像。 临床流行病学计划，高级光学成像和扩散MRI分析科学。 支撑研究，他的平行职业发展计划，一个敬业和经验导师的团队以及一个 世界一流的环境，基尔申博士将实现他的目标，以否决独立的神经护理 小儿心脏骤停后特别关注神经系统复苏的研究科学家。