Advancing Epilepsy Diagnosis with Flexible, High-Resolution Thin-Film Electrodes

项目摘要 为了推动新一代个人化治疗方法的发展，以长期解除癫痫发作，我们 迫切需要技术来改善癫痫诊断，同时降低与侵入性疾病相关的风险 神经外科手术。在100多万患有失控的局灶性癫痫的美国人中，许多人 局部性癫痫发作灶较差。这些人面临着最高的失败率(即持续的癫痫发作) 在癫痫手术后。这一失败反映了他们癫痫的生物学特征以及癫痫发作灶与 基本的皮质区域。然而，当前技术的局限性也是导致高故障率的关键因素，因为 我们目前在对新皮质的大范围区域进行采样(即立体脑电)或记录大范围脑电方面的能力有限 不会引起疼痛、肿胀和神经炎性组织损害的新皮质区域(即硬膜下网格 和脱衣录音)。 为了满足对更安全、更有效的侵入性电极研究的需求，同时使发现 先进的下一代疗法，这个UG3/UH3临床试验项目利用一个成功的、长期的 临床医生、工程师、材料科学家、神经科学家和行业合作伙伴在New 纽约大学医学院、杜克大学、犹他大学、黑石大学 MicroSystems和Dyconex将现代薄膜技术转化为FDA批准的下一代 植入式神经装置。我们已经开发并广泛测试了一种新型的电极阵列，该阵列基于 液晶聚合物薄膜(LCP-TF)技术与合作伙伴Dyconex，AG。当与大规模的 数据采集系统，LCP-TF电极将提供比现有FDA更高质量的神经记录 经批准的电极阵列，具有改进的安全性和可承受的成本。 我们建议从FDA获得传统的510(K)批准，用于短期植入LCP-TF(&lt；30天) 电极：(1)改善新皮质、局灶性、耐药癫痫患者的手术耐受性 正在进行侵入性电极研究和(2)先进的诊断能力，以确定 癫痫灶。我们在非人类灵长类动物模型中的初步工作导致了一个几乎相同的原型装置 到计划用于临床测试的最终设备设计。这项工作为进入建立了支持数据 为期3年的UG3阶段(目标1-3)的临床前测试，将导致510(K)批准的设备(目标4)用于 在为期2年的UH3阶段(目标5)进行的单地点随机对照试点临床试验，将检验该假设 使用LCP-Tf电极进行癫痫诊断研究，与CG电极相比，两者都有改善 手术耐受性和诊断有效性。这些努力将推动下一代的发展 治疗癫痫的精确方法以及支持LCP-Tf电极的未来发展 神经紊乱。FDA批准的低成本LCP-Tf电极有可能彻底改变 治疗多种神经性疾病

Project Summary To advance the development of next-generation personalized therapies for long-term seizure freedom, we urgently need technologies that improve seizure diagnostics while reducing risks associated with invasive neurosurgical procedures. Among the more than 1,000,000 Americans with uncontrolled focal epilepsy, many have poorly localized seizure foci. These individuals face the highest rates of ‘failure’ (i.e., ongoing seizures) after epilepsy surgery. That failure reflects the biology of their epilepsy as well as the overlap of seizure foci with essential cortical areas. However, limits of current technologies also play a critical role in the high failure rate as we are currently limited in our ability to sample wide regions of the neocortex (i.e., stereoEEG) or to record broad neocortical regions without inducing pain, swelling, and neuroinflammatory tissue damage (i.e., subdural grid and strip recordings). To meet this need for safer, more effective invasive electrode studies and simultaneously enable discovery to advance next-generation therapies, this UG3/UH3 clinical trial project leverages a successful, long-term collaboration between clinicians, engineers, material scientists, neuroscientists and industrial partners at New York University School of Medicine, New York University, Duke University, the University of Utah, Blackrock Microsystems, and Dyconex to translate modern thin-film technology into next generation FDA-approved implantable neurological devices. We have developed and extensively tested a novel electrode array based on liquid crystal polymer thin-film (LCP-TF) technology with partner Dyconex, AG. When combined with large-scale data acquisition systems, LCP-TF electrodes will provide higher quality neural recordings than existing FDA approved electrode arrays, with improved safely and at an affordable cost. We propose to obtain traditional 510(k) approval from the FDA for short-term implantation (<30 days) of LCP-TF electrodes to (1) improve surgical tolerability for patients with neocortical, focal, drug-resistant epilepsy undergoing invasive electrode studies and (2) advance diagnostic capabilities to determine the location of seizure foci. Our preliminary work in a non-human primate animal model led to a prototype device nearly identical to the final device design planned for clinical testing. This work establishes supporting data for entry into preclinical testing in the 3-year UG3 phase (Aims 1-3) that will lead to 510(k)-approved devices (Aim 4) for a single-site, randomized-controlled pilot clinical trial in the 2-year UH3 phase (Aim 5) that will test the hypothesis that performing epilepsy diagnostic studies with LCP-TF electrodes, compared to CG electrodes, improves both surgical tolerability and diagnostic effectiveness. These efforts will advance the development of next-generation precision approaches to treating epilepsy as well as support future development of LCP-TF electrodes for other neurological disorders. Low-cost, FDA-approved LCP-TF electrodes have the potential to revolutionize the treatment of a wide range of neurological disorders