Development and Translation of an Intracranial Auditory Nerve Implant

摘要 该项目将建立和评估一种新型颅内听觉系统的安全性和设计需求， 针对耳蜗和脑干之间的听神经的假体（听神经植入物，ANI） 为了在当前的护理标准上显著改善听力性能，耳蜗植入物 （CI）。目前的CI为许多接受者提供了关键的语音信息，但不能恢复正常的听力， 在嘈杂或复杂的声学环境中尤其具有挑战性。尽管在过去的共同努力下， 25年来，CI性能几乎没有得到全面改善，主要是由于电极性能差， 其中CI电极浸入耳蜗液中并与听觉分离的神经界面 耳蜗骨壁的神经。新方法将建立在动物研究的令人鼓舞的数据基础上， 成熟的人类手术技术进入听神经，高密度电极和安全 目前可供人类使用的刺激技术，以测试ANI的安全性和有效性 这使得电极和听觉神经之间能够直接接触。ANI提供了巨大的承诺， 改善其潜在受众的语音和音乐感知，通过克服挑战， 在过去的四分之一世纪，CI的改善有限。第一个目标是设计和建立一个完整的ANI系统 符合法规要求，包括必要的可靠性、安全性、功能性、生物相容性， 和人类使用的灭菌测试。ANI系统将通过结合成熟的CI设备来构建 在听觉植入领域，已经在人体中评估了新的电极和电缆技术， 患者用于其他临床应用。第二个目标是在人尸体上完善ANI手术 在其他相关的体内操作期间， 电极阵列和电缆连接到目标区域。第三个目标是开发和验证关键的 心理物理测试，以适当评估ANI在初步人体研究期间的表现，这可以 然后通知未来临床ANI设备的设计。第四个目标是寻求监管部门的批准， 临床试验基础设施和监测实体。第五个也是最后一个目标是在最多的国家进行试点ANI研究。 三个耳聋患者获得安全性，可靠性和功能性数据，可以正确指导设计， 进行临床装置和可行性研究。

ABSTRACT The proposed project will build and evaluate the safety and design needs of a new type of intracranial auditory prosthesis that targets the auditory nerve between the cochlea and the brainstem (auditory nerve implant, ANI) in order to substantially improve hearing performance over the current standard of care, the cochlear implant (CI). Current CIs provide crucial speech information to many recipients, but do not restore normal hearing, and are particularly challenged in noisy or complex acoustic environments. Despite concerted efforts over the past 25 years, little overall improvement in CI performance has been obtained, primarily due to the poor electrode- neural interface in which the CI electrodes are immersed in cochlear fluids and separated from the auditory nerve by the cochlea's bony wall. The new approach will build upon encouraging data from animal studies, well-established human surgical techniques to access the auditory nerve, and high-density electrode and safe stimulation technologies currently available for human use in order to test the safety and efficacy of the ANI that enables direct contact between the electrodes and the auditory nerve. The ANI provides great promise of improved speech and music perception for its prospective recipients, by overcoming the challenge that has limited improvements in CIs for the past quarter century. The first aim is to design and build a full ANI system in accordance with regulatory requirements, including necessary reliability, safety, functional, biocompatibility, and sterilization testing for human use. The ANI system will be built by combining a well-established CI device in the auditory implant field with a novel electrode and cabling technology already being evaluated in human patients for other clinical applications. The second aim is to refine the ANI surgery in human cadaver experiments and acutely during other relevant in vivo operations to consistently position and anchor the electrode array and cabling into the target region. The third aim is to develop and validate critical psychophysical tests to properly evaluate the performance of the ANI during the pilot human study, which can then inform the design of a future clinical ANI device. The fourth aim is to seek regulatory approvals and set up the clinical trial infrastructure and monitoring entities. The fifth and final aim is to perform a pilot ANI study in up to three deaf patients to obtain safety, reliability and functionality data that can properly guide the design of a proceeding clinical device and a feasibility study.