Diagnosing outer hair cell health along the cochlear partition

感音神经性听力损失是由于耳蜗内和听觉内的各种结构受损所致。 很有胆量。目前，基因和组织移植策略正在探索作为治疗策略 治愈听力损失。不幸的是，没有可用的诊断技术来隔离和区分 耳蜗神经或听神经损伤的解剖部位(S)。一个测试电池，它能识别出 病变(S)将允许医生针对适当的解剖位置进行医疗干预。长期的 这项研究的目标是开发这些诊断测试。在本提案中，R21阶段的目标是 确定耳蜗声是否为麦克风(CM)，以响应嵌入在高通中的低频音 噪声，可以用来量化沿耳蜗区丢失的外毛细胞的位置。一次累积 外毛细胞的分布函数(CDF)是通过绘制掩蔽的CM相对于 特定掩码频率的未屏蔽幅度。我们假设地球上一个高原的位置 CDF(或CDF中的某个其他变量或相应的概率密度函数)将与该位置相关 丢失的外毛细胞。这是通过将丢失的外毛细胞的位置与 毛细胞损伤动物的CDF和解剖学测量。在临床人群中，外毛细胞可能 在场但功能不正常。在R33阶段，我们开发了毛细胞换能器的指标 决定幸存的外毛细胞健康状况的功能。我们假设1)换能器的功能 可以获得沿耳蜗长的指标，以及2)这些指标可以量化外毛细胞的健康 尽管对其他耳蜗结构造成了损害。第一个目标是通过将高原的位置关联起来进行测试 具有暂时性听力损失的动物的最大听力损失位置的指数的CDF 不同的频率。第二个假设是通过比较不同动物群体之间的指数来检验的 损害到外毛细胞和其他结构。 这项提案中的研究很可能适用于人类患者。目前，CM记录在 美国和欧洲的听力学诊所。未来优化刺激和记录位置的研究是 被设想为下一步开发与新的医疗疗法相辅相成的诊断测试 正在探索的治疗感音神经性听力损失的策略。

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.