Intraoperative Localization of Epileptic Brain Regions Under Sevoflurane Anesthesia.

七氟烷麻醉下癫痫脑区域的术中定位。

• 批准号: 10678530
• 负责人: Ethan Joseph Firestone
• 金额: $ 4.74万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-10 至 2025-07-09
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678530
• 关键词: 3-Dimensional; Anatomy; Anesthesia procedures; Anesthetics; Area; Atlases; Biological Markers; Brain; Brain imaging; Brain region; Child; Childhood; Clinical; Cognitive deficits; Cohort Studies; Consumption; Coupling; Critical Thinking; Data; Development; Diagnostic; Drug resistance; Electrodes; Electroencephalography; Entropy; Epilepsy; Ethics; Etiology; Evaluation; Event; Excision; FDA approved; Fellowship; Fostering; Foundations; Grant; High Frequency Oscillation; Human; Intervention; Intractable Epilepsy; Isoflurane; Lesion; Logistics; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medical; Michigan; Modeling; Observational Study; Operating Rooms; Operative Surgical Procedures; Outcome; Partial Epilepsies; Pathway interactions; Patients; Pediatric Hospitals; Pediatric Surgical Procedures; Phase; Physicians; Postoperative Period; Procedures; Process; Protocols documentation; Proxy; Regimen; Research; Research Design; Resected; Risk Factors; Risk Reduction; Scientist; Seizures; Signal Transduction; Site; Slow-Wave Sleep; Specificity; Techniques; Testing; Time; Training; Travel; Visual; Visualization; Volatilization; brain tissue; career; cost effectiveness; implantation; improved; indexing; insight; neural; neurophysiology; pediatric patients; prospective; repository; sevoflurane; standard care; success; tool; tractography; treatment optimization; white matter

Drug-resistant, focal epilepsy impacts millions of children, and treatment often requires invasive evaluation. This process entails identification of intracranial electroencephalography (iEEG) biomarkers such as spike-and-wave discharges (SWDs), to guide surgical removal of the presumed epileptogenic zone responsible for generating habitual seizures. In pediatric patients, extra-operative iEEG evidence indicated that a SWD proxy measuring coupling between delta wave phase and high-frequency oscillation (HFO) amplitude – Modulation Index (MI) – accurately tracks epileptogenicity. Since MI does not detail the causality of neural propagations, it’s powerful to also consider iEEG Transfer Entropy (TE), which measures effective connectivity, and dynamic tractography to provide plausible propagation pathways. Granted, capturing adequate interictal and ictal epileptic events often requires days of extra-operative iEEG recording, and this procedure is grueling, expensive, and replete with major risk factors. Thus, development of intra-operative techniques for induction and reliable measurement of epileptic iEEG biomarkers is imperative to avoid the above pitfalls and help expand utility of one-stage procedures. Pertinently, sevoflurane anesthesia reversibly activates spike activity, but there is much debate over its specificity. Preliminary iEEG results in children suggest that sevoflurane may intra-operatively augment both MI and HFO effective connectivity (TE) in seizure foci. However, large cohort studies are needed to validate this finding, as it is unknown how sevoflurane impacts intra-operative MI and HFO-TE in healthy versus epileptogenic brain areas and if these signals spread via major white matter tracts. Thus, the main aims of the current proposal are to: 1) build normative atlases of intra-operative MI and HFO-TE, at varying concentrations of sevoflurane, and 2) determine if sevoflurane-induced modulation of these features can localize seizure foci and predict seizure outcomes. To accomplish these aims, the trainee will map patient electrodes to 3-dimensional magnetic resonance brain images, quantify the intra-operative iEEG metrics at stepwise increases of sevoflurane, and combine iEEG effective connectivity with white matter tractography (i.e. dynamic tractography). Characterizing the endogenous distribution of MI and HFO effective connectivity, with and without sevoflurane, will provide critical baseline reference for iEEG interpretation. In addition, understanding how sevoflurane impacts these metrics in epileptic networks is expected to improve interictal localization efforts during surgery, reduce invasive diagnostic burden by mitigating the need for extra-operative recording, optimize treatment cost effectiveness, and ultimately improve seizure outcomes. Through this project, the trainee will: (1) gain insight into and help refine clinical epilepsy treatment, (2) enhance scientific understanding of how neural oscillatory coupling and effective connectivity respond under sevoflurane, and (3) will undergo a training regimen to foster development of critical thinking and hypothesis-driven, ethical research design. The cumulative effect of the research and didactics will provide a critical foundation for the trainee’s career as a physician-scientist.

耐药性局灶性癫痫影响数百万儿童，治疗通常需要侵入性评估。这 这一过程需要识别颅内脑电图（iEEG）生物标志物，如棘波和波 放电（SWD），以指导手术切除负责产生癫痫的假定致痫区 习惯性癫痫在儿科患者中，手术外iEEG证据表明，SWD替代测量 三角波相位与高频振荡（HFO）振幅之间的耦合-调制指数（MI）- 准确地追踪致癫痫性由于多元智能没有详细说明神经传播的因果关系，它对 还可以考虑iEEG传输熵（TE），它可以测量有效的连接性，以及动态纤维束描记术， 提供合理的传播路径。诚然，捕捉足够的发作间期和发作癫痫事件往往 需要几天的额外手术iEEG记录，这个过程是艰苦的，昂贵的，充满了 主要风险因素。因此，开发用于诱导和可靠测量的术中技术， 癫痫iEEG生物标志物是必要的，以避免上述陷阱，并有助于扩大实用性的一个阶段 程序.七氟醚麻醉可逆地激活棘波活性，但有很多争议 超过了它的特异性。儿童的初步iEEG结果表明，七氟烷可在术中增加 MI和HFO在癫痫灶中的有效连接（TE）。然而，需要大规模的队列研究来验证 这一发现，因为尚不清楚七氟烷如何影响健康人与 致癫痫脑区，如果这些信号通过主要的白色物质束传播。因此， 目前的建议是：1）建立术中MI和HFO-TE的规范性图谱， 七氟烷浓度，和2）确定七氟烷诱导的这些特征的调节是否可以 定位癫痫灶并预测癫痫发作结果。为了实现这些目标，受训者将映射病人 电极到三维磁共振脑图像，量化术中iEEG指标， 逐步增加七氟烷，并将联合收割机iEEG有效连接与白色纤维束描记术（即 动态纤维束成像）。表征MI和HFO有效连通性的内源性分布， 和无七氟烷时，将为iEEG解释提供关键基线参考。此外，理解 七氟烷如何影响癫痫网络中的这些指标，预计将改善发作间期定位工作 在手术过程中，通过减少对手术外记录的需求， 治疗成本效益，并最终改善癫痫发作的结果。通过本项目，学员将：（1） 深入了解并帮助完善临床癫痫治疗，（2）提高对神经系统如何 振荡耦合和有效的连接反应下七氟烷，（3）将接受训练方案 培养批判性思维和假设驱动的道德研究设计。累计影响 的研究和教学将提供一个重要的基础，为受训者的职业生涯作为一个医生，科学家。