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着数百万儿童，治疗通常需要侵入性评估。 该过程需要识别颅内脑电图 (iEEG) 生物标志物，例如棘波和波 放电（SWD），以指导手术切除负责产生癫痫的推定致痫区 在儿科患者中，术外 iEEG 证据表明 SWD 替代测量。 δ波相位和高频振荡 (HFO) 幅度之间的耦合 – 调制指数 (MI) – 由于 MI 没有详细说明神经传播的因果关系，因此它的功能非常强大。 还可以考虑 iEEG 传递熵 (TE)，它测量有效的连接性和动态纤维束描记术 当然，通常可以捕获足够的发作间期和发作期癫痫事件。 需要数天的术外 iEEG 记录，这个过程非常艰苦、昂贵，而且充满了 因此，开发用于诱导和可靠测量的术中技术。 癫痫 iEEG 生物标志物对于避免上述陷阱并帮助扩大一阶段的效用至关重要 相应地，七氟烷麻醉可逆地激活尖峰活动，但存在很多争议。 儿童的初步 iEEG 结果表明七氟醚可能会在术中增强作用。 MI 和 HFO 在癫痫病灶中均有效连接 (TE) 然而，需要大型队列研究来验证。 这一发现，因为目前尚不清楚七氟醚如何影响健康人与手术中的 MI 和 HFO-TE 致癫痫的大脑区域以及这些信号是否通过主要白质束传播。 目前的建议是：1）建立术中 MI 和 HFO-TE 的规范图集，在不同的情况下 七氟醚的浓度，以及 2) 确定七氟醚诱导的这些特征的调节是否可以 为了实现这些目标，学员将绘制患者地图。 将电极连接到 3 维磁共振脑图像，量化术中 iEEG 指标 逐步增加七氟烷，并将 iEEG 有效连接与白质纤维束描记相结合（即 动态纤维束成像）。表征 MI 和 HFO 有效连接的内源分布， 并且没有七氟醚，将为 iEEG 解释提供关键的基线参考。 七氟醚如何影响癫痫网络中的这些指标有望改善发作间期定位工作 在手术期间，通过减少术外记录的需要来减少侵入性诊断负担，优化 通过该项目，学员将：(1) 深入了解并帮助完善临床癫痫治疗，(2) 增强对神经元如何发挥作用的科学理解 振荡耦合和有效连接在七氟烷下响应，并且 (3) 将接受训练方案 促进批判性思维和假设驱动的道德研究设计的发展。 研究和教学将为学员作为医师科学家的职业生涯提供重要的基础。