Diagnosing outer hair cell health along the cochlear partition

感音神经性听力损失是由耳蜗和听觉内各种结构的损伤引起的 神经。目前，正在探索遗传和组织移植策略作为治疗策略， 治疗听力损失不幸的是，没有可用的诊断技术来分离和区分 耳蜗或听神经内损伤的解剖部位。一种测试电池，用于识别 病变将允许医生瞄准适当的解剖部位进行医疗干预。长期 这项研究的目的是开发这些诊断测试。在本提案中，R21阶段的目标是 确定耳蜗颤噪音（CM）是否响应于嵌入在高通滤波器中的低频音调， 噪声可以用于量化沿着耳蜗分区沿着缺失的外毛细胞的位置。累计 外毛细胞的分布函数（CDF）通过绘制掩蔽CM的振幅相对于 特定掩蔽频率的未掩蔽振幅。我们假设高原的位置 CDF（或CDF中的某个其他变量或对应的概率密度函数）将与位置相关 外毛细胞的缺失这是通过将缺失的外毛细胞的位置与由神经细胞的位置估计的外毛细胞的位置相关联来测试的。 毛细胞病变动物的CDF和解剖测量。在临床人群中，外毛细胞可能 存在但功能异常。在R33阶段，我们从毛细胞换能器开发指数 决定存活的外毛细胞的健康状况。我们假设：1）传感器功能 可以沿着耳蜗的长度获得指数，以及2）指数可以量化外毛细胞健康 尽管对其他耳蜗结构有损伤。第一个目标是通过关联高原的位置进行测试 在暂时性听力损失的动物中， 各种频率。第二个假设是通过比较各组动物的指数来检验的， 外毛细胞和其他结构的病变。 该提案中的研究可能会转化为人类患者。目前，CM记录在 美国和欧洲的听力诊所。未来的研究优化刺激和记录位置是 被设想为下一步发展的诊断测试，恭维新的医疗 感音神经性听力损失的治疗策略。

Sensorineural hearing loss results from damage to a variety of structures within the cochlea and auditory nerve. Presently, genetic and tissue transplantation strategies are being explored as therapeutic strategies for curing hearing loss. Unfortunately there are no available diagnostic techniques that isolate and distinguish the anatomic site(s) of damage within the cochlea or auditory nerve. A test battery that identifies the locus of lesion(s) will allow physicians to target the appropriate anatomic sites for medical intervention. The long-term goal of this research is to develop these diagnostic tests. In this proposal, the aim of the R21 phase is to determine if the cochlear microphonic (CM), in response to a low-frequency tone embedded in high-pass noise, can be used to quantify the location of missing outer hair cells along the cochlear partition. A cumulative distribution function (CDF) of outer hair cells is obtained by plotting the amplitude of the masked CM relative to the unmasked amplitude for specific masker frequencies. We hypothesize that the location of a plateau in the CDF (or some other variable in the CDF or corresponding probability density function) will relate to the location of missing outer hair cells. This is tested by correlating the location of missing outer hair cells estimated by the CDF with anatomic measurements in animals with hair cell lesions. In clinic populations, outer hair cells may be present but functioning abnormally. In the R33 phase we develop indices from hair cell transducer functions to determine the health of surviving outer hair cells. We hypothesize that 1) transducer function indices can be obtained along the length of the cochlea and 2) the indices can quantify outer hair cell health despite damage to other cochlear structures. The first goal is tested by correlating the location of the plateau of the CDF of an index with the location of maximum hearing loss in animals with temporary hearing loss at various frequencies. The second hypothesis is examined by comparing indices among groups of animals with lesions to outer hair cells and other structures. The studies in this proposal are likely to be translated to human patients. Presently, the CM is recorded in Audiologic clinics in the United States and Europe. Future studies optimizing stimuli and recording location are envisioned as the next step for developing diagnostic tests that compliment the new medical treatment strategies that are being explored to cure sensorineural hearing loss.