Inner Ear Fluid Interactions

描述（由申请人提供）：内耳液紊乱是许多临床疾病的原因。目前的研究主要集中在内淋巴容积紊乱与内耳功能的关系上。已经开发了对小的内淋巴体积干扰敏感的生理测量，即使耳蜗敏感性未受损。它们基于偶数阶失真（二次谐波（2f），f2-f1和f2+f1发射），当Corti器官从其正常静止位置移位时，这些失真会发生变化，从而改变毛细胞的转导特性。耳蜗换能器的“工作点”可以从耳蜗颤噪和微创声发射记录中得出。在干扰操作点或内淋巴体积的操作期间，将表征失真和操作点之间的相互关系。将结果与预测失真对工作点的依赖性的模型进行比较。通过声发射记录记录异常内淋巴容量状态的能力具有临床相关性，因为它可以诊断内淋巴积水。还将研究以微创方式操纵内耳液体的技术。药物在耳蜗中的分布将在其应用于圆窗膜后通过各种方案进行量化。新的外淋巴液采样技术将用于记录耳蜗中的纵向药物梯度。药物在耳朵中的分布模型将被细化，并用于预测药物在人耳中的分布模式。3D模型将与我们现有的内耳流体模拟进行比较。将测量与内淋巴体积紊乱和恢复相关的生理变化。将筛选可能影响内淋巴体积的处理。这些综合研究的结果预计将直接影响梅尼埃病的诊断和治疗。

DESCRIPTION (provided by applicant): Disturbances of the inner ear fluids are responsible for a number of clinical disorders. The proposed studies focus on the relationships between endolymph volume disorders and inner ear function. Physiologic measures have been developed that are sensitive to small endolymph volume disturbances even when cochlear sensitivity is not impaired. They are based on even-order distortions (second harmonic (2f), f2-f1 and f2+f1 emissions) that change when the organ of Corti is displaced from its normal resting position, thereby altering hair cell transduction properties. Cochlear transducer "operating point" can be derived from cochlear microphonic and from less-invasive acoustic emissions recordings. The interrelationships between distortions and operating point will be characterized during manipulations that disturb operating point or endolymph volume. Results will be compared with models that predict the dependence of distortion on operating point. The ability to document abnormal endolymph volume states through acoustic emissions recordings is clinically relevant as it may allow endolymphatic hydrops to be diagnosed. Techniques for manipulating inner ear fluids in a minimally invasive manner will also be investigated. The distribution of drugs in the cochlea will be quantified following their application to the round window membrane with a variety of protocols. Novel perilymph sampling techniques will be used to document longitudinal drug gradients in the cochlea. Models of drug distribution in the ear will be refined and used to predict drug distribution patterns in the human ear. 3-D models will be compared with our existing simulations of inner ear fluids. Physiologic changes associated with endolymph volume disturbance and recovery will be measured. Treatments will be screened that could potentially influence endolymph volume. The findings from these combined studies are expected to directly impact both the diagnosis and management of Meniere's disease.