Diagnosing outer hair cell health along the cochlear partition

描述（由申请人提供）： 感音神经性听力损失是由耳蜗和听神经内的各种结构受损引起的。目前，基因和组织移植策略正在探索作为治疗听力损失的治疗策略。不幸的是，没有可用的诊断技术来隔离和区分耳蜗或听神经内的损伤的解剖部位。识别病变部位的测试组合将允许医生瞄准适当的解剖部位进行医疗干预。这项研究的长期目标是开发这些诊断测试。在该提议中，R21阶段的目的是确定响应于嵌入高通噪声中的低频音调的耳蜗颤噪（CM）是否可以用于量化沿着耳蜗分区沿着缺失的外毛细胞的位置。外毛细胞的累积分布函数（CDF）通过绘制特定掩蔽频率的掩蔽CM相对于未掩蔽振幅的振幅来获得。我们假设CDF中平台的位置（或CDF中的一些其他变量或相应的概率密度函数）将与缺失的外毛细胞的位置相关。这是通过将CDF估计的缺失外毛细胞的位置与毛细胞病变动物的解剖测量相关联来测试的。在临床人群中，外毛细胞可能存在，但功能异常。在R33阶段，我们开发了毛细胞换能器功能的指数，以确定存活的外毛细胞的健康状况。我们假设：1）换能器功能指数可以沿着耳蜗的长度沿着获得，2）这些指数可以量化外毛细胞的健康状况，尽管对其他耳蜗结构有损伤。第一个目标是通过将指数的CDF的平台的位置与在各种频率下具有暂时性听力损失的动物中的最大听力损失的位置相关联来测试的。第二个假设是通过比较外毛细胞和其他结构损伤的动物组之间的指数来检验的。 该提案中的研究可能会转化为人类患者。目前，CM在美国和欧洲的听力诊所记录。优化刺激和记录位置的未来研究被设想为开发诊断测试的下一步，这些测试补充了正在探索的治疗感音神经性听力损失的新医疗策略。 公共卫生相关性： 听力损失是由内耳和听神经内的各种解剖结构的损伤引起的。目前，有一个科学和医学的运动，以治疗听力损失的基因和/或组织移植技术。不幸的是，没有诊断技术可以识别特定患者听力损失的基础结构的位置和健康状况。这项研究的目的是开发诊断测试，确定病变的部位，使医生可以指导新的医学治疗，以适当的目标。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Hearing loss is caused by damage to a variety of anatomic structures both within the inner ear and auditory nerve. Presently, there is both a scientific and medical movement towards curing hearing loss with genetic and/or tissue transplantation techniques. Unfortunately there are no diagnostic techniques that can identify the location and health of the structures underlying hearing loss in a particular patient. The goal of this research is to develop diagnostic tests that identify the locus of lesion so that physicians can direct new medical treatments to the appropriate target.