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.

项目摘要 詹妮弗·A·金（Jennifer A.她的长期 职业目标是成为具有信号处理专业知识的独立资助的转化调查员 神经生理学和神经影像学数据，以识别重病患病的早期生物标志物 患者，特别是与创伤后癫痫有关的患者。创伤后癫痫是一种残疾的并发症 创伤性脑损伤（TBI）。迫切需要寻找创伤后癫痫的生物标志物来识别 患有这种并发症的高风险患者。这是早期生物标志物识别的人群 可以改善患者监测并最终治疗发育以规避癫痫发生。邮政- 创伤性癫痫有助于使TBI发病率，残疾和成本的率恶化 护理，因此强调了防止这种并发症的重要性。我们需要找到最佳的生物标志物 定义最有可能受益的人，并使此类发现试验更多 可行的。在拟议的培训期间，候选人将根据她对脑电图信号的了解 加工和机器学习技术，并使用磁性获得神经影像分析的新技能 共振技术和生物统计学。为此，金博士汇集了一个强大的 Hal Blumenfeld博士（小学导师）和联合主管Drs的指导团队。托德·康斯特布尔（Todd Constable），布兰登（Brandon） Westover和Brian Edlow在研究癫痫，功能性MRI方面具有专业知识 分析，计算脑电图分析和结构TBI成像。在他们的指导下，金博士 提出至：1）量化癫痫样异常（EA）频率并确定EA波形特征 最佳预测PTE，2）确定通过皮质厚度和挫伤评估的直接海马损伤是否直接损伤 数量，分层PTE风险3）评估基于结构和功能的间接海马损伤是否是 MRI连接分析，Portend PTE。总体目标是确定高风险患者的早期生物标志物 用于创伤后癫痫，以靶向抗癫痫发作的发展。汇聚 高级神经生理学和神经影像学分析以及强大的指导支持，该项目开放 用于优化后续护理和推进所有创伤的潜在治疗开发的新途径 脑损伤患者有创伤后癫痫的风险。这项定义明确的以患者为导向的研究建议， 与指导和结构化教学课程的音乐会，将为Kim博士提供技能 发展神经生理学和神经影像学研究的独立职业至关重要，该研究转化为 改善患者的预后。