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

项目摘要 为了促进下一代个性化治疗的发展，以实现长期无癫痫发作，我们 迫切需要技术，改善癫痫诊断，同时减少与侵入性疾病相关的风险。 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， 癫痫灶定位不好这些人面临着最高的“失败”率（即，正在进行的缉获） 癫痫手术后这种失败反映了他们癫痫的生物学以及癫痫灶与癫痫的重叠。 重要的皮质区然而，当前技术的局限性也在高故障率中起着关键作用， 我们目前在对新皮层的宽区域进行采样的能力方面受到限制（即，立体EEG）或记录宽 新皮层区域而不引起疼痛、肿胀和神经炎性组织损伤（即，硬膜下网格 和条带记录）。 为了满足对更安全、更有效的侵入性电极研究的需求，同时能够发现 先进的下一代疗法，这个UG 3/UH 3临床试验项目利用了一个成功的，长期的 临床医生，工程师，材料科学家，神经科学家和工业合作伙伴之间的合作， 约克大学医学院、纽约约克大学、杜克大学、犹他州大学、贝莱德 微系统公司和Dyconex将现代薄膜技术转化为FDA批准的下一代产品 可植入的神经系统装置我们已经开发并广泛测试了一种新型电极阵列， 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 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LCP-TF短期植入（<30天）的传统510（k）批准 电极（1）改善新皮质、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和（2）先进的诊断能力，以确定位置 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设备 计划用于临床试验的最终器械设计。这项工作建立了支持数据， 3年UG 3阶段的临床前试验（目标1-3），将导致510（k）批准器械（目标4）， 将检验假设的2年UH 3期（目标5）的单中心、随机对照初步临床试验 与CG电极相比，使用LCP-TF电极进行癫痫诊断研究， 手术耐受性和诊断有效性。这些努力将推动下一代的发展 精确的方法来治疗癫痫，并支持未来开发LCP-TF电极，用于其他 神经系统疾病低成本、FDA批准的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