Seizure localization for epilepsy surgery using high frequency electrophysiological markers

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， 患者可受益于手术切除产生肿瘤的脑组织。在手术之前， 通常直接植入患者的大脑中或大脑上， 活动日。这样做是为了捕捉癫痫发作活动并确定其起源点，即癫痫发作 起始区如果识别出癫痫发作区，则临床医生随后将该信息与 脑成像和其他测试的结果，以指导相应脑组织的切除。虽然癫痫 手术可能导致癫痫发作的自由，70-90%的手术患者保持抗癫痫药物， 大约50%的病人继续癫痫发作。这项工作的长期目标是改善成果 通过开发更准确的方法来定位癫痫发生， 组织.高频振荡（HFO）因其识别 定位致癫痫脑组织HFO是高频电活动的短暂爆发， 癫痫病人的大脑它们更频繁地发生在致痫区（EZ，假设的 必须切除以获得术后癫痫发作自由的区域），并通过手术切除产生HFO的 脑组织会增加癫痫发作的可能性虽然正在进行的临床试验试图评估 虽然它们对癫痫手术规划的前瞻性价值，但它们的广泛使用存在多种障碍。而 组水平的结果是稳健的，HFO分析还不能预测单个受试者。记录缺乏 可靠地测量每个患者的HFO的灵敏度，非癫痫HFO的发生混淆了 结果因此，HFO有望彻底改变癫痫手术，但迫切需要优化 最大限度地提高单个受试者的准确性。本建议的总体目标是改善 通过系统地确定最佳HFO测量方法来提高EZ定位精度， 再加上新的，强大的HFO分析方法。基本原理是，开发这些新方法 随着测量技术的改进，将提高HFO作为生物标志物的准确性和鲁棒性。 癫痫发作区，从而改善癫痫的外科治疗。为了实现我们的目标，我们将 具体目标有三：（1）证明电极尺寸是HFO测量的关键因素。（二） 开发基于HFO的患者特定EZ定位的自动化方法。(3)评价 电极尺寸和HFO分析方法对EZ定位的影响。所提出的研究是有意义的 因为它将为氢氟烯烃的测量和分析提供具体的建议， 准确详细地定位致癫痫脑组织这项工作的预期成果是， 指导外科医生选择要切除的大脑区域， 候选人总的来说，这将产生积极的影响，导致更大的机会癫痫发作的自由， 改善最严重癫痫患者的生活质量。

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.