Establishing the maximum safe stimulation parameters for platinum cochlear implant electrode arrays.

建立铂人工耳蜗电极阵列的最大安全刺激参数。

• 批准号: 9331628
• 负责人: Robert K Shepherd
• 金额: $ 31.16万
• 依托单位: UNIVERSITY OF MELBOURNE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9331628
• 关键词: Acoustic Nerve; Acute; Adopted; Adult; Animals; Area; Auditory; Charge; Child; Chronic; Clinic; Clinical; Cochlea; Cochlear Implants; Communities; Custom; Development; Devices; Electric Stimulation; Electrodes; Electrophysiology (science); Growth; Guidelines; Hearing; Implanted Electrodes; Industry Standard; Manufacturer Name; Measures; Medical; Metabolic; Metabolic stress; Neurons; Osteogenesis; Outcome; Patients; Phase; Physiologic pulse; Platinum; Property; Reaction; Research; Safety; Scala Tympani; Stimulus; Surface; Techniques; Technology; Tissues; United States Food and Drug Administration; Work; base; density; design; experience; hearing impairment; improved; insight; instrumentation; neural prosthesis; next generation; platinum electrode; preclinical study; public health relevance; relating to nervous system; response

 DESCRIPTION (provided by applicant): Cochlear implants stimulate the auditory nerve using stimuli that minimize the release of toxic electrochemical byproducts and damage associated with metabolic stress of the stimulated neurons. However, these guidelines were based on acute stimulation of cortical neurons and thus do not reflect the safe levels of stimulation for us in a cochlear implant. This application will establish safe stimulation limits specifically for cochlear implants using chronic electrical stimulation. The project will use clinical implants and electrode fabrication technology to manufacture customized electrode arrays for this research with carefully defined surfaces as small as 0.05 mm2. We hypothesize that safe stimulation levels will be significantly greater than the present levels defined by acute studies. If this hypothesis is correct the next generation of cochlear implants could include smaller electrodes and new stimulation strategies leading to improved clinical outcomes for cochlear implant users. This project has three specific aims: i) establish the threshold stimulus levels for electrochemical damage using platinum electrodes. In this study stimulus rate and charge per phase will be held constant while charge density will be varied from 100-400 µC/cm2/phase using purpose built electrode arrays. The prime measures used to evaluate the extent of electrochemical damage will be the degree of tissue response in stimulated versus control cochleae, neural survival and evidence of electrode degradation; ii) establish the threshold stimulus parameters giving rise to metabolic damage following chronic electrical stimulation of the auditory nerve. This study will co-vary charge per phase (0.39-0.78 µC/phase; i.e. from "safe" to the "unsafe" levels defined acutely), stimulation rate (250 - 1000 pulses per second) and duty cycle (25 - 100%). These combinations will allow us to examine the effects of each parameter independently. Metabolic damage is expected to specifically target auditory neurons and therefore electrophysiological response properties and neural survival will be the primary measures to establish the extent of damage and to define safe limits in both chronically stimulated versus control cochleae; and iii) establish the interaction between electrochemical and metabolic damage by co-varying charge density, charge per phase, stimulation rate and duty cycle around the safe / unsafe boundaries determined in aims i) and ii). These results will allow us to determine the extent of interaction, if any, between the electrochemical and metabolic damage, again impacting on safe stimulation levels.

 描述（由应用提供）：人工耳蜗使用刺激刺激听觉神经，从而最大程度地减少有毒电化学副产品的释放以及与刺激神经元的代谢应力相关的损伤。但是，这些准则基于对皮质神经元的急性刺激，因此不能反映我们在人工耳蜗中对我们的安全刺激水平。该应用将使用慢性电模拟建立专门针对人工耳蜗的安全刺激极限。该项目将使用临床直接和 电极制造技术，用于制造本研究的定制电极阵列，仔细定义的表面小至0.05 mm2。我们假设安全刺激水平将显着大于急性研究定义的当前水平。如果该假设是正确的，那么下一代的人工耳蜗可能包括较小的电极和新的刺激策略，从而改善了人工耳蜗使用者的临床结果。项目具有三个特定的目的：i）使用铂电极建立电化学损伤的阈值刺激水平。在这项研究中，使用专用的电极阵列，刺激速率和电荷将保持恒定，而电荷密度将与10​​0-400 µC/cm2/phoe不同。用于评估电化学损伤程度的主要措施将是刺激与对照耳蜗的组织反应程度，神经存活以及电极降解的证据。 ii）建立慢性电刺激听觉神经后，建立阈值刺激参数。这项研究将每个阶段共同充电（0.39-0.78 µC/阶段；即从“安全”到急性定义的“不安全”水平），刺激率（每秒250-1000脉冲）和占空比（25-100％）。这些组合将使我们能够独立检查每个参数的效果。预计代谢损伤将专门针对听觉神经元，因此电生理反应的特性和神经生存将是确定损害程度并定义两个长期刺激的损害程度并定义安全限制的主要措施； iii）通过电荷密度，每相电荷，刺激速率和占空比的相互作用建立电化学和代谢损伤之间的相互作用，围绕在目标i）和II中确定的安全 /不安全边界周围。这些结果将使我们能够确定电化学和代谢损害之间的相互作用程度（如果有的话），从而再次影响了安全刺激水平。