Improving Sound Perception with an Advanced Intracochlear Electrode Array and Integrated Insertion Platform

主要研究者：Bhatti，Pamela提案编号：1133625本提案的研究目的是检验以下假设：与当代耳蜗电极阵列相比，使用聚合物高密度电极阵列的耳蜗内电刺激能够更集中和选择性地激活听觉神经元。为了实现研究目标，我们必须开发一种方法，将柔性高密度阵列与硅胶插入平台（IP）集成，并对集成设备进行机械、电气、体外和最终体内测试。我们将研究分为两个阶段。在第一阶段，我们将重点关注使用已经在人类中验证的IP，以及（a）微制造薄膜阵列并将其与IP集成，（B）使用3D人类耳蜗模型，通过弯曲测试和插入研究机械地验证集成阵列，以及通过阻抗测量电气地验证集成阵列，以及（c）在猫模型中比较高密度阵列与当代阵列的脑内电刺激的功效。在第二阶段，我们利用第一阶段建立的方法，通过将薄膜阵列与模制硅胶插入平台集成，开发出专门针对猫模型的阵列。全世界有超过180，000人使用人工耳蜗，许多人实现了高水平的语音识别。但是仍然有一组患者在嘈杂的环境中实现较差的语音识别和难以理解语音。克服这一挑战的一种潜在手段是提供具有高密度阵列的电到神经接口之间的增强耦合。用当代的制造方法实现这样的阵列是不可能的，其中阵列由封装在硅树脂中的线束手工构造。耳蜗中没有足够的空间来扩大这种方法。这一建议是第一次努力将基于薄膜的阵列与IP集成在一起。这是一种变革性的方法，因为它利用了微加工薄膜提供的精细特征分辨率（1微米），并将此类阵列与在人类中验证的当代阵列的相同机械灵活性，尺寸和特征的IP相结合。此外，引入集成的高密度阵列大小的猫模型将使基础研究探索和比较新的电场成形策略，如电流导向和电流聚焦，用于优化电神经接口。更广泛的IMPLENT集成薄膜阵列打开了一个主机的可能性，以进一步提高患者的性能与人工耳蜗植入。最近的研究已经说明了组合电（高频）和声（低频）刺激对于改善言语感知的益处，特别是在嘈杂的环境中。一个重要的组成部分是插入耳蜗底部的短（10 mm）阵列，通过最大限度地减少创伤来保留任何剩余的低频神经元件。通过将平台的机械设计与阵列分离，我们的方法能够在保持高密度电极配置的同时继续开发创伤较小的平台。 此外，将薄膜阵列与插入平台集成可以使得这样的阵列能够接近其他结构，诸如刺激前庭（平衡）假体的前庭神经纤维以及潜在地深部脑刺激以减轻帕金森病、癫痫和抑郁症。 为了扩大代表性不足的群体的参与，PI保持她的研究与推广，指导和教学相结合的战略，以吸引学生在整个K-毕业生连续体。这包括在Fernbank科学中心（佐治亚州亚特兰大）举办的"科学之夜"，以及与当地初中/高中教师共同开发科学模块。她在她的生物系统接口实验室指导本科生和研究生研究人员，辅导少数民族学生，并正在创建一个研究生水平的混合生物系统课程，解决前庭，耳蜗和心脏生物系统。PI开发了人工耳蜗信号处理器的LabVIEW仿真，作为IEEE真实的世界工程项目，支持免费开放许可的教育材料，从而使她能够接触到国际学生/教师群体。最后，PI正在与当地的人工耳蜗社区合作，为她实验室的聋人学生创造本科生和研究生的研究机会。

PI: Bhatti, PamelaProposal Number: 1133625The research objective of this proposal is to test the hypothesis that intracochlear electrical stimulation with a polymeric high-density electrode array enables a more focused and selective activation of auditory neurons when compared with contemporary cochlear electrode arrays. To achieve the research objective we must develop a method for integrating a flexible high-density array with a silicone insertion platform (IP), and test the integrated device mechanically, electrically, in-vitro, and eventually in-vivo. We divide the proposed research into two phases. In Phase I we will focus on using an IP that has been validated in humans and (a) microfabricate and integrate a thin-film array with the IP, (b) using a 3D human cochlear model, validate the integrated array mechanically through bend tests and insertion studies, and electrically by impedance measurement, and (c) compare the efficacy of intracochlear electrical stimulation of the high-density array with a contemporary array in the cat model. In Phase II we leverage the methods established in Phase I to develop an array specifically sized for the cat model by integrating a thin-film array with a molded silicone insertion platform. INTELLECTUAL MERIT Over 180,000 individuals use cochlear implants worldwide and many achieve a high level of speech recognition. But there remains a group of patients achieving poor speech recognition and difficulty understanding speech in noisy environments. One potential means to overcome this challenge is to provide an enhanced coupling between the electrical to neural interface with a high-density array. Implementing such an array is impossible with contemporary fabrication methods where arrays are constructed by hand from bundles of wire encased in silicone. There simply is not enough room in the cochlea to scale up this method. This proposal is the first effort at integrating a thin-film based array with an IP. This is a transformative approach as it leverages the fine feature resolution (1ìm) offered by microfabricated thin-films and combines such arrays with an IP commanding the same mechanical flexibility, dimensions and features of contemporary arrays validated in humans. Furthermore, the introduction of integrated high-density arrays sized for the cat model will enable fundamental studies exploring and comparing novel electric fields shaping strategies, such as current steering and current focusing, employed to optimize the electrical-to-neural interface.BROADER IMPACTS Integrated thin-film arrays open a host of possibilities to further improve patient performance with cochlear implants. Recent studies have illustrated the benefit of combined electrical (high frequency) and acoustic (low frequency) stimulation for improving speech perception, especially in noisy environments. An important component is a short (10mm) array inserted into the base of the cochlea that preserves any remaining low frequency neural elements by minimizing trauma. By decoupling the mechanical design of the platform from the array, our approach enables continued development of less traumatic platforms while retaining the high-density electrode configuration. Furthermore, integrating a thin-film array with an insertion platform may enable such arrays to approach other structures such as stimulation of vestibular nerve fibers for a vestibular (balance) prosthesis and potentially deep brain stimulation to mitigate Parkinson's disease, epilepsy and depression. To broaden the participation of underrepresented groups, the PI maintains a strategy for integrating her research with outreach, mentoring, and teaching to engage students across the K-graduate continuum. This includes "Science Nights" at the Fernbank Science Center (Atlanta, GA) and codeveloping science modules with local middle/high schoolteachers. She guides undergraduate and graduate researchers in her BioSystems Interface Lab, mentors minority students, and is creating a graduate-level Hybrid Biosystems course addressing vestibular, cochlear and cardiac biosystems. The PI has developed a LabVIEW simulation of a cochlear implant signal processor as an IEEE Real World Engineering Project supporting free open-licensed educational materials thereby enabling her to reach an international student/teacher population. And finally, the PI is partnering with the local cochlear implant community to create undergraduate and graduate research opportunities for deaf students in her lab.