Physiology-driven seizure management post-cardiac arrest

项目总结/摘要 博士Edilberto Amorim是一名神经学家，在重症监护和癫痫方面接受过亚专业培训， 脑监测生物医学技术创新，为缺氧患者提供个性化治疗， 心脏骤停后缺血性脑损伤这个职业发展奖及其严格的课程将 Amorim博士是一名临床科学家，在以下领域拥有独立的专业知识：1）深度学习应用于 生理学时间序列，2）观察数据的因果推断，和3）定量脑成像。每 每年，超过50万美国人心脏骤停。脑损伤是死亡的头号原因， 患者在初始复苏后存活，难治性癫痫发作和其他癫痫样脑活动， 高达50%的患者被确诊。尽管这是一种常见的并发症，但结果令人沮丧， 心脏骤停后癫痫发作的治疗策略是有限的。阿莫林博士旨在确定生理驱动的 通过利用最先进的计算方法， 拥有超过1,500名受试者的海量EEG和神经成像数据集。他的核心假设是特定的时间- 在心脏骤停治疗期间，棘波和伴随的EEG活动的依赖性变化预测癫痫发作 控制并最终恢复神经功能本建议的主要目标是：1）尽早识别 纵向癫痫样脑电图表型预测神经功能恢复的可解释性和深度 2）建立癫痫发作治疗对麻醉剂反应的定量EEG生物标志物; 和3）估计用麻醉剂快速治疗癫痫发作在防止结构性脑损伤中的因果作用。 脑MRI定量损伤。阿莫林博士已经生成了初步数据，以证明 对EEG表型进行纵向建模以预测结果，并应用了定量EEG生物标志物 以预测脑MRI的脑损伤程度。他在这项提案中的主要导师将是爱德华·张博士，一位 神经科学家和人类神经生理学研究的领导者。他的共同导师将包括布兰登博士 Westover是机器学习应用于重症监护EEG的权威，Donna Ferriero博士是一位 在缺氧缺血性脑损伤方面完成了翻译和神经影像学研究。额外 定量神经成像（Srikantan Nagarajan博士）和生物统计学（Charles McCulloch博士）的指导将 是他训练的重要组成部分这些目标有望建立早期非侵入性预测 神经恢复和癫痫发作控制的生物标志物可能：1）指导临床试验的患者选择 富集和2）用作缺氧缺血性脑损伤后治疗干预的靶点。通过 利用世界级导师组成的跨学科团队的深厚专业知识和无与伦比的 阿莫林博士将在加州大学、旧金山弗朗西斯科和湾区的创新环境中， 理想地定位于揭示关于急性脑损伤后癫痫发生的基础知识， 率先开展临床试验，重点是改善对心脏骤停患者有意义的结果。

PROJECT SUMMARY/ABSTRACT Dr. Edilberto Amorim is a neurologist with subspecialty training in critical care and epilepsy who aims to employ biomedical technology innovations in brain monitoring to personalize treatment for patients with hypoxic- ischemic brain injury post-cardiac arrest. This career development award and its rigorous curriculum will establish Dr. Amorim as a clinician-scientist with independent expertise in: 1) Deep learning applied to physiology time-series, 2) Causal inference for observational data, and 3) Quantitative brain imaging. Every year, more than 500,000 Americans have a cardiac arrest. Brain injury is the number one cause of death for patients surviving initial resuscitation, and refractory seizures and other seizure-like brain activity are diagnosed in up to 50% of patients. Despite being a common complication, outcomes are dismal and current treatment strategies for seizures post-cardiac arrest are limited. Dr. Amorim aims to identify physiology-driven biomarkers of resilience to hypoxic-ischemic brain injury by utilizing state-of-the-art computational methods and a massive EEG and neuroimaging dataset with >1,500 subjects. His central hypothesis is that specific time- dependent changes in spike and accompanying EEG activity during cardiac arrest treatment predict seizure control and, ultimately, neurological recovery. The primary objectives of this proposal are: 1) Identify early longitudinal epileptiform EEG phenotypes predictive of neurological recovery using interpretable and deep learning algorithms; 2) Establish quantitative EEG biomarkers of seizure treatment response to anesthetics; and 3) Estimate the causal effect of rapid seizure treatment with anesthetics in preventing structural brain injury quantified with brain MRI. Dr. Amorim has generated preliminary data to demonstrate the feasibility of modeling EEG phenotypes longitudinally for outcome prediction and has applied quantitative EEG biomarkers to predict degree of brain injury on brain MRI. His primary mentor in this proposal will be Dr. Edward Chang, a neuroscientist and leader in human neurophysiology research. His co-mentors will include Dr. Brandon Westover, an authority in machine learning applied to critical care EEG, and Dr. Donna Ferriero, an accomplished translational and neuroimaging investigator in hypoxic-ischemic brain injury. Additional mentoring in quantitative neuroimaging (Dr. Srikantan Nagarajan) and biostatistics (Dr. Charles McCulloch) will be essential components of his training. These aims are expected to establish early non-invasive predictive biomarkers of neurological recovery and seizure control that may: 1) Guide patient selection for clinical trials enrichment and 2) Serve as target to therapeutic interventions after hypoxic-ischemic brain injury. By leveraging the deep expertise of a cross-disciplinary group of world-class mentors and the unparalleled innovation environments of the University of California, San Francisco and the Bay Area, Dr. Amorim will be ideally positioned to uncover fundamental knowledge about epileptogenesis after acute brain injury as well as spearhead clinical trials focused on improving outcomes meaningful to cardiac arrest patients.