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: 10192851
• 负责人: Jennifer A Kim
• 金额: $ 19.11万
• 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/10192851
• 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; Diagnostic radiologic examination; 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; 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.

项目摘要 博士Jennifer A. Kim是耶鲁-纽黑文医院的重症监护神经学家和神经科学家。她的长期 我的职业目标是成为一名独立资助的翻译研究员，具有信号处理方面的专业知识 神经生理学和神经影像学数据，以确定重症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 患者有发生这种并发症的高风险。这是一个早期生物标志物鉴定 可以改善病人的监测和最终的治疗开发，以避免癫痫发生。后 创伤性癫痫导致已经很高的TBI发病率、残疾率和治疗费用的恶化。 因此，强调预防这种并发症的重要性。我们需要找到生物标记物 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多 可行在建议的培训期间，候选人将扩大她对EEG信号的了解 处理和机器学习技术，并获得神经成像分析的新技能， 共振技术和生物统计学。为了实现这一目标，金博士召集了一个强大的 由Hal Blumenfeld博士（主要导师）和共同导师托德·康斯特布尔博士、布兰登博士组成的导师团队 Westover和Brian Edlow在研究癫痫的多模式方法，功能性MRI 分析，计算EEG分析和结构TBI成像。在他们的指导下，金博士 提出：1）量化癫痫样异常（EA）频率并识别 最佳预测PTE，2）确定是否直接海马损伤，通过皮质厚度和挫伤评估 3）根据结构和功能评估是否存在间接海马损伤 MRI连通性分析，预示PTE。总体目标是确定高危患者的早期生物标志物 用于创伤后癫痫，以开发抗癫痫治疗。汇集 先进的神经生理学和神经影像学分析和这种强大的导师支持，这个项目打开 优化随访护理和推进所有创伤性疾病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。这一明确的以患者为导向的研究提案， 音乐会与导师和结构化的教学课程，将提供金博士的技能， 在神经生理学和神经影像学研究中发展独立的职业生涯至关重要， 从而改善患者结果。