Seizure localization for epilepsy surgery using high frequency electrophysiological markers

使用高频电生理标记进行癫痫手术的癫痫发作定位

• 批准号: 10570953
• 负责人: Beth Ann Lopour
• 金额: $ 34.24万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570953
• 关键词: Accounting; Anticonvulsants; Antiepileptic Agents; Area; Biological Markers; Blinded; Brain; Brain imaging; Brain region; Characteristics; Classification; Clinical; Clinical Trials; Complex; Coupled; Data; Decision Making; Detection; Electrocorticogram; Electrodes; Electroencephalography; Electrophysiology (science); Epilepsy; Event; Excision; Failure; Freedom; Frequencies; Goals; High Frequency Oscillation; Implant; Implanted Electrodes; Individual; Intuition; Knowledge; Measurement; Measures; Methodology; Methods; Modeling; Monitor; Morphology; Operative Surgical Procedures; Outcome; Pathologic; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Physiological; Postoperative Period; Procedures; Prospective Studies; Quality of life; Recommendation; Research; Resected; Seizures; Sensitivity and Specificity; Signal Transduction; Specificity; Surface; Surgeon; Surgical Management; Techniques; Testing; Tissues; Vision; Work; brain electrical activity; brain tissue; childhood epilepsy; clinical implementation; computerized tools; density; high standard; improved; improved outcome; minimally invasive; neurotransmission; novel; prospective; risk minimization; simulation

PROJECT SUMMARY/ABSTRACT In the most severe cases of epilepsy, where seizures persist despite multiple trials of anti-seizure medications, patients may benefit from surgical removal of seizure-generating brain tissue. Prior to surgery, electrodes are often implanted directly into or onto the patient’s brain and are used to continuously record electrical brain activity over days. This is done to capture seizure activity and determine its point of origin, i.e. the seizure onset zone. If the seizure onset zone is identified, clinicians then use this information, in combination with the results of brain imaging and other testing, to guide removal of the corresponding brain tissue. While epilepsy surgery may lead to seizure freedom, 70-90% of surgery patients remain on anti-seizure medications and roughly 50% of patients continue to have seizures. The long-term goal of this work is to improve the outcomes of patients undergoing epilepsy surgery by developing more accurate methods to localize seizure-generating tissue. High frequency oscillations (HFOs) have garnered considerable excitement for their potential to identify and localize epileptogenic brain tissue. HFOs are short bursts of high-frequency electrical activity that occur in the brains of patients with epilepsy. They occur more frequently in the epileptogenic zone (EZ, the hypothetical area that must be excised to attain post-operative seizure freedom), and surgically removing HFO-generating brain tissue increases the likelihood of seizure freedom. While ongoing clinical trials are attempting to assess their prospective value for epilepsy surgery planning, there are multiple barriers to their widespread use. While group-level results are robust, HFO analysis is not yet predictive for single subjects. Recordings lack the sensitivity to reliably measure HFOs in every patient, and the occurrence of non-epileptic HFOs confounds the results. Therefore, HFOs are poised to revolutionize epilepsy surgery, but there is a critical need to optimize their measurement and maximize single-subject accuracy. The overall objective of this proposal is to improve EZ localization accuracy through systematic determination of the optimal HFO measurement methodology, coupled with novel, robust methods for HFO analysis. The rationale is that developing these novel methods with improved measurement techniques will increase the accuracy and robustness of HFOs as a biomarker of the seizure onset zone, thus improving the surgical management of epilepsy. To attain our objective, we will pursue three specific aims: (1) Demonstrate that electrode size is a crucial factor in HFO measurement. (2) Develop an automated method for patient-specific localization of the EZ based on HFOs. (3) Evaluate the effects of electrode size and HFO analysis method on EZ localization. The proposed research is significant because it will provide specific recommendations for the measurement and analysis of HFOs, enabling accurate, detailed localization of epileptogenic brain tissue. The expected outcome of this work is that it will guide surgeons in choosing which brain regions to remove and will increase the pool of potential surgical candidates. Overall, this will have a positive impact by leading to a greater chance of seizure freedom and improved quality of life for patients with the most severe cases of epilepsy.

项目概要/摘要 在最严重的癫痫病例中，尽管进行了多次抗癫痫药物试验，癫痫发作仍持续存在， 患者可能会受益于手术切除引起癫痫发作的脑组织，在手术前放置电极。 通常直接植入患者的大脑，用于连续记录脑电 这样做是为了捕获癫痫发作活动并确定其起源点，即癫痫发作。 如果确定了癫痫发作区域，则人群可以结合使用该信息。 脑部影像学等检测结果，指导切除相应的脑组织而进行癫痫治疗。 手术可能会导致癫痫发作消失，70-90% 的手术患者仍在服用抗癫痫药物，并且 大约 50% 的患者持续出现癫痫发作 这项工作的长期目标是改善结果。 通过开发更准确的方法来定位癫痫发作的患者接受癫痫手术 高频振荡（HFO）因其识别组织的潜力而引起了人们的极大兴趣。 HFO 是发生在脑组织中的短时高频电活动。 癫痫患者的大脑中，它们更常见于致癫痫区（EZ，假设的区域）。 必须切除的区域才能实现术后癫痫发作），并通过手术去除产生 HFO 的区域 脑组织增加了无癫痫发作的可能性，而正在进行的临床试验正在尝试评估。 它们对于癫痫手术规划的预期价值，虽然其广泛使用存在多种障碍。 团体层面的结果是稳健的，但 HFO 分析尚无法对单个受试者进行预测。 可靠地测量每位患者的 HFO 的敏感性，并且非癫痫性 HFO 的出现混淆了 因此，HFO 有望彻底改变癫痫手术，但迫切需要优化。 该提案的总体目标是提高其测量结果并最大限度地提高单个受试者的准确性。 通过系统确定 HFO 测量方法实现最佳 EZ 定位精度， 结合新颖、稳健的 HFO 分析方法，其基本原理是开发这些新颖的方法。 改进的测量技术将提高 HFO 作为生物标志物的准确性和稳健性 癫痫发作区，从而改善癫痫的手术治疗 为了实现我们的目标，我们将 追求三个具体目标： (1) 证明电极尺寸是 HFO 测量的关键因素。 开发一种基于 HFO 的 EZ 患者特异性定位的自动化方法 (3) 评估。 电极尺寸和 HFO 分析方法对 EZ 定位的影响本研究具有重要意义。 因为它将为 HFO 的测量和分析提供具体建议，从而使 这项工作的预期结果是准确、详细地定位致癫痫脑组织。 指导外科医生选择要切除的大脑区域，并将增加潜在的手术机会 总体而言，这将产生积极影响，使他们有更大的机会摆脱癫痫发作。 改善最严重癫痫患者的生活质量。