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: 10487553
• 负责人: Matthew P Kirschen
• 金额: $ 17.89万
• 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/10487553
• 关键词: Acute Brain Injuries; Affect; Age; Anisotropy; Bilateral; Biometry; Blood Pressure; Brain; Brain Injuries; Brain imaging; Cardiac; Caring; Categories; Cerebrovascular Circulation; Cerebrovascular system; Cerebrum; Characteristics; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Critical Care; Data; Development Plans; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Doctor of Philosophy; Environment; Event; Fellowship; Foundations; Future; Goals; Heart Arrest; Homeostasis; Hospitals; Hour; Hypoxia; Imaging Techniques; Impairment; Intervention Trial; Knowledge; Lead; 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; Radial; Research; Resuscitation; Scientist; Secondary to; Severities; Spectrum Analysis; Testing; Time; Training; Training Programs; Translating; Universities; age related; arterial spin labeling; base; blood pressure control; career; career development; cerebral hypoperfusion; clinical epidemiology; clinical practice; 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 儿童心脏骤停很常见，导致高发病率和死亡率。 高达 80% 的心脏骤停幸存儿童会发生心脏骤停后的脑损伤。 最初的缺氧缺血事件以及随后数小时至数天内发生的继发性脑损伤。 心脏骤停后护理的重点是减少继发性脑损伤。 脑血管扩张或收缩以维持脑血管相对恒定的生理过程 平均动脉血压 (MAP) 范围内的血流量 (CBF) 会导致大脑受损。 容易受到低灌注和高灌注状态的影响，这可能导致继发性脑损伤和 关于 CAR 最完整的 MAP，存在可预防的神经功能障碍。 小儿心脏骤停后，以及偏离最佳 MAP 对脑损伤和临床的影响 该提案的中心假设是 MAP 之间存在较大差异的患者。 心脏骤停后最佳 MAP 会导致更差的脑微结构损伤和临床结果。 对于该提案，将使用先进的非侵入性光学成像技术直接测量 CBF 称为扩散相关光谱 (DCS) 的技术将用于计算最佳 MAP Brain。 损伤将使用扩散磁共振成像（MRI）进行量化。主要临床结果是。 出院时的神经功能障碍基于儿科脑功能类别。 拟议研究的目的是确定与 DCS 偏差较大的患者是否 确定的最佳 MAP 具有更差的临床结果（目标 1）和扩散时的微结构脑损伤 与最佳 MAP 偏差较小的患者进行 MRI（目标 2）比较 此外，还进行了局部 CBF。 来自 DCS 的 CBF 将与来自动脉自旋标记 (ASL) MRI 的 CBF 相关（目标 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​​脑生理学目标管理策略的试验提供信息 改善儿童心脏骤停的结果 申请人 Matthew Kirschen 博士是一名儿科重症监护医生和 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的研究 小儿心脏骤停、脑生理学方面的教学课程培训和专家指导 他将通过硕士学位获得临床生物统计学方面的专业知识。 临床流行病学计划、先进光学成像和扩散 MRI 分析科学。 拟议的研究、他的并行职业发展计划、一支敬业且经验丰富的导师团队，以及 世界一流的环境，Kirschen 博士将实现成为独立神经重症监护人的目标 研究科学家，特别关注小儿心脏骤停后的神经复苏。