EEG and MRI Biomarkers to Predict Post-traumatic Epilepsy

脑电图和 MRI 生物标志物可预测创伤后癫痫

• 批准号: 10448381
• 负责人: Jennifer A Kim
• 金额: $ 18.98万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10448381
• 关键词: Acute; Acute Brain Injuries; Address; Admission activity; Algorithms; Animals; Antiepileptogenic; Atrophic; Award; Benchmarking; Biological Markers; Biometry; Blinded; Brain Injuries; Caring; Characteristics; Chronic; Cognition; Collection; Complication; Contusions; Critical Care; Critical Illness; Data; Development; Development Plans; Disease; Early identification; Electroencephalography; Enrollment; Epilepsy; Epileptogenesis; Foundations; Frequencies; Functional Imaging; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Hemorrhage; Heterogeneity; Hippocampus (Brain); Hospitals; Human; Image; Image Analysis; Injury; Intervention; Knowledge; Lead; Lesion; Location; Machine Learning; Magnetic Resonance; Magnetic Resonance Imaging; Malignant - descriptor; Measures; Mentors; Mentorship; Methods; Monitor; Morbidity - disease rate; Multicenter Trials; Neurologist; Outcome; Paper; Patient Monitoring; Patient imaging; Patient-Focused Outcomes; Patients; Phase; Population; Post-Traumatic Epilepsy; Prevention trial; Provider; Publishing; Research; Research Proposals; Resolution; Rest; Risk; Rodent Model; Sclerosis; Secondary to; Seizures; Severities; Structure; TBI Patients; Techniques; Technology; Thick; Training; Translating; Traumatic Brain Injury; United States National Institutes of Health; Work; axon injury; base; biomarker development; biomarker identification; care costs; career; career development; cost estimate; didactic education; disability; early detection biomarkers; follow-up; high risk; hippocampal atrophy; human imaging; imaging biomarker; imaging study; improved; magnetic resonance imaging biomarker; multimodality; neuroimaging; neuroimaging marker; neurophysiology; patient biomarkers; patient oriented research; prediction algorithm; predictive marker; prevent; preventable epilepsy; prospective; radiological imaging; risk stratification; signal processing; skills; therapy development; tool; translational scientist; treatment trial; white matter

Project Summary Dr. Jennifer A. Kim is a critical care neurologist and neuroscientist at Yale-New Haven Hospital. Her long-term career goal is to become an independently funded translational investigator with expertise in signal processing of neurophysiologic and neuroimaging data to identify early biomarkers of secondary brain injury in critically ill patients, particularly related to post-traumatic epilepsy. Post-traumatic epilepsy is a disabling complication of traumatic brain injury (TBI). There is an urgent need to find biomarkers of post-traumatic epilepsy to identify patients at high risk for developing this complication. It is a population in which early biomarker identification could improve patient monitoring and ultimately treatment development to circumvent epileptogenesis. Post- traumatic epilepsy contributes to worsening of the already high rates of TBI morbidity, disability and cost of care, thus emphasizing the importance of preventing this complication. We need to find biomarkers to best define those most likely to benefit from potential treatments and make such treatment discovery trials more feasible. During the proposed training period, the candidate will expand upon her knowledge of EEG signal processing and machine learning techniques and acquire new skills in neuroimaging analysis using Magnetic Resonance technologies and biostatistics. To accomplish this, Dr. Kim has brought together a strong mentorship team of Dr. Hal Blumenfeld (primary mentor) and co-mentors Drs. Todd Constable, Brandon Westover and Brian Edlow who have expertise in multi-modal approaches to studying epilepsy, functional MRI analysis, computational EEG analysis and structural TBI imaging, respectively. Under their mentorship, Dr. Kim proposes to: 1) quantify epileptiform abnormality (EA) frequency and identify EA waveform features that optimally predict PTE, 2) determine if direct hippocampal injury, assessed by cortical thickness and contusion volume, stratifies PTE risk 3) assess whether indirect hippocampal injury, based on structural and functional MRI connectivity analyses, portend PTE. The overall goal is to identify early biomarkers of patients at high risk for post-traumatic epilepsy to target development of anti-epileptogenesis treatments. Bringing together advanced neurophysiologic and neuroimaging analysis and this strong mentorship support, this project opens new avenues for optimizing follow-up care and advancing potential treatment development for all traumatic brain injury patients at risk for post-traumatic epilepsy. This well-defined patient-oriented research proposal, in concert with the mentorship and structured didactic curriculum, will provide Dr. Kim with the skills that are essential to develop an independent career in neurophysiological and neuroimaging research that translates to improving patient outcomes.

项目概要 Jennifer A. Kim 博士是耶鲁-纽黑文医院的重症监护神经科医生和神经科学家。她的长期 职业目标是成为一名独立资助的具有信号处理专业知识的转化研究者 神经生理学和神经影像学数据，以确定危重患者继发性脑损伤的早期生物标志物 患者，特别是与创伤后癫痫有关的患者。创伤后癫痫是一种致残性并发症 创伤性脑损伤（TBI）。迫切需要找到创伤后癫痫的生物标志物来识别 发生这种并发症的高风险患者。这是一个早期生物标志物识别的人群 可以改善患者监测并最终开发治疗方法以避免癫痫发生。邮政- 创伤性癫痫导致本已很高的 TBI 发病率、残疾率和治疗费用进一步恶化 护理，从而强调预防这种并发症的重要性。我们需要找到最好的生物标志物 定义那些最有可能从潜在治疗中受益的人，并使此类治疗发现试验更加有效 可行的。在建议的培训期间，候选人将扩展她对脑电图信号的了解 处理和机器学习技术，并使用 Magnetic 获得神经影像分析的新技能 共振技术和生物统计学。为了实现这一目标，金博士汇集了强大的 Hal Blumenfeld 博士（主要导师）和共同导师 Drs. 的导师团队。托德·康斯特勃尔、布兰登 Westover 和 Brian Edlow 拥有研究癫痫、功能性 MRI 的多模式方法方面的专业知识 分别是分析、计算脑电图分析和结构 TBI 成像。在他们的指导下，Kim 博士 建议：1) 量化癫痫样异常 (EA) 频率并识别 EA 波形特征 最佳预测 PTE，2) 确定是否存在直接海马损伤，通过皮质厚度和挫伤进行评估 体积，分层 PTE 风险 3) 根据结构和功能评估是否存在间接海马损伤 MRI 连接性分析预示着 PTE。总体目标是识别高危患者的早期生物标志物 针对创伤后癫痫，以开发抗癫痫发生治疗为目标。汇聚在一起 先进的神经生理学和神经影像分析以及强大的指导支持，该项目启动 优化后续护理和推进所有创伤患者潜在治疗开发的新途径 脑损伤患者有患创伤后癫痫的风险。这项明确的以患者为导向的研究计划， 与指导和结构化教学课程相结合，将为 Kim 博士提供以下技能： 对于在神经生理学和神经影像学研究领域发展独立的职业生涯至关重要 改善患者的治疗效果。