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

项目概要 为了推进下一代个性化疗法的开发，以实现长期无癫痫发作，我们 迫切需要改进癫痫诊断的技术，同时降低与侵入性相关的风险 神经外科手术。在超过 1,000,000 名患有不受控制的局灶性癫痫的美国人中，许多人 癫痫病灶定位不佳。这些人面临最高的“失败”率（即持续癫痫发作） 癫痫手术后。这种失败反映了他们癫痫的生物学特性以及癫痫病灶与癫痫病灶的重叠。 重要的皮质区域。然而，当前技术的局限性也是导致高故障率的一个关键因素： 目前，我们对新皮质大范围区域（即立体脑电图）进行采样或记录大范围区域的能力受到限制。 新皮质区域不会引起疼痛、肿胀和神经炎性组织损伤（即硬膜下网格 和条带录音）。 为了满足对更安全、更有效的侵入性电极研究的需求，同时使发现能够 为了推进下一代疗法，该 UG3/UH3 临床试验项目利用了成功的长期 New 临床医生、工程师、材料科学家、神经科学家和工业合作伙伴之间的合作 约克大学医学院、纽约大学、杜克大学、犹他大学、贝莱德大学 Microsystems 和 Dyconex 将现代薄膜技术转化为 FDA 批准的下一代技术 植入式神经设备。我们开发并广泛测试了一种基于 与合作伙伴 Dyconex, AG 合作的液晶聚合物薄膜 (LCP-TF) 技术。当与大规模结合时 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，以可承受的成本安全地进行改进。 我们建议获得 FDA 对 LCP-TF 短期植入（<30 天）的传统 510(k) 批准 电极 (1) 提高新皮质、局灶性、耐药性癫痫患者的手术耐受性 进行侵入性电极研究以及（2）先进的诊断能力以确定电极的位置 癫痫病灶。我们在非人类灵长类动物模型中的初步工作产生了几乎相同的原型设备 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支持数据 3 年 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） 为期 2 年的 UH3 阶段（目标 5）的单中心、随机对照试点临床试验将检验该假设 与 CG 电极相比，使用 LCP-TF 电极进行癫痫诊断研究可以改善两者 手术耐受性和诊断效果。这些努力将推动下一代的发展 治疗癫痫的精确方法，并支持其他领域 LCP-TF 电极的未来开发 神经系统疾病。经 FDA 批准的低成本 LCP-TF 电极有可能彻底改变 治疗多种神经系统疾病

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