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: 10368114
• 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/10368114
• 关键词: Accounting; 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; Lead; 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; base; brain electrical activity; brain tissue; childhood epilepsy; clinical implementation; computerized tools; density; feature detection; 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.

项目摘要/摘要 在最严重的癫痫病例中，尽管多次试验抗癫痫药物，癫痫仍在发作， 患者可能受益于手术切除导致癫痫发作的脑组织。在手术前，电极是 通常被直接植入或植入患者的大脑中，用于连续记录脑电 连续几天的活动。这样做是为了捕捉癫痫活动并确定其起源点，即癫痫发作 起始区。如果确定了癫痫发作的起始区，临床医生就会将这一信息与 脑部成像等检测结果，指导切除相应脑组织。而癫痫 手术可能导致癫痫缓解，70%至90%的手术患者仍在服用抗癫痫药物和 大约50%的患者仍有癫痫发作。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产生，对接受癫痫手术的患者进行评估 组织。高频振荡(HFO)因其识别的潜力而引起了相当大的兴奋 并定位致痫的脑组织。HFO是短时爆发的高频电活动，发生在 癫痫患者的大脑。它们更多地出现在致痫区域(EZ，假设的 必须切除以获得术后癫痫自由的区域)，并通过手术移除产生HFO的区域 脑组织增加了癫痫发作自由的可能性。而正在进行的临床试验试图评估 它们对于癫痫手术计划的预期价值，它们的广泛使用存在着多重障碍。而当 群体水平的结果是稳健的，HFO分析对单个受试者还不能预测。录音缺少 在每个患者中可靠地测量HFO的敏感性，以及非癫痫HFO的发生使 结果。因此，高频电切手术有望给癫痫手术带来革命性的变化，但仍有迫切的需要进行优化 他们的测量，并最大限度地提高单一受试者的准确性。这项建议的总体目标是改进 通过系统确定最佳HFO测量方法的EZ定位精度， 与新的、稳健的HFO分析方法相结合。其基本原理是开发这些新方法 改进的测量技术将增加HFO作为生物标志物的准确性和稳健性 癫痫的起始区，从而改进了癫痫的外科治疗。为了达到我们的目标，我们将 追求三个具体目标：(1)证明电极尺寸是测量HFO的关键因素。(2) 开发一种基于HFOS的患者特定EZ定位的自动化方法。(3)评估 电极尺寸和HFO分析方法对EZ局部化的影响。这项拟议的研究具有重要意义 因为它将为衡量和分析HFO提供具体建议，从而使 准确、详细的致痫脑组织定位。这项工作的预期结果是，它将 指导外科医生选择要切除的大脑区域，并将增加潜在的外科手术池 候选人。总体而言，这将产生积极影响，导致更大的扣押自由和 改善最严重癫痫患者的生活质量。