Biomechanical Measurement and Modeling of Normal and Diseased Middle Ears

描述（申请人提供）：中耳由听骨和鼓膜、韧带、关节等软组织组成，在声音的传递和听觉中起着至关重要的作用。中耳炎等中耳疾病中软组织的力学特性发生改变。因此，听骨链的活动性降低，在中耳炎耳中发生显著的传导性听力损失。然而，与疾病相关的软组织力学特性变化在很大程度上尚未得到研究。根据目前的临床工具，几乎不可能识别与听力损失有关的中耳组织的力学变化。本项目的目标是表征正常和病变耳中软组织的生物力学行为，识别与正常听力变化相关的软组织变化，并提供改进的三维（3D）耳模型，以可视化和量化各种疾病中的结构-功能关系。中耳炎（OM）将是该项目的主要焦点。本研究提出了三个具体目的：目的1：确定OM中耳软组织力学特性的变化。我们假设耳膜组织力学特性的变化与耳膜组织在液体、压力和持续时间下的形态学变化有关。通过动态力学分析仪、分离式霍普金森张力杆、激光多普勒振动仪（LDV）声驱动、条纹Moiri系统和软组织有限元模型对龙猫正常和病变耳组织测量结果的比较，验证了这一假设。目的2：量化中耳生物力学变化对OM中声音传播的影响。据推测，OM的听力损失是由耳组织、液体和中耳压力的变化共同引起的。本文将通过测量鼠耳的ABR阈值、中耳传递函数和声能传递的变化来验证这一假设，并结合鼠耳的有限元模型，对鼠耳的流体、压力和组织特性进行新颖的理论分析，以描述鼠耳的机制。目标3：继续开发具有临床应用价值的人耳三维有限元模型。我们将在模型中加入Aims 1和Aims 2中确定的组织特性，TM和ISJ的微观结构以及镫骨肌功能。为研究幼儿OM，建立小儿耳部FE模型。病变耳中耳的声-机械振动和能量传递将通过模型推导的4条新型“听觉测试曲线”在三维有限元模型中进行可视化和量化，分别为：中耳传递函数（METF）、能量吸收（EA）、导纳鼓膜图（AT）和TM全息图，帮助医生和听力学家解释诊断测试结果，识别中耳疾病的具体类型。

DESCRIPTION (provided by applicant): The middle ear, composed of ossicles and soft tissues including the tympanic membrane, ligaments, and joints plays a vital role in the transmission of sound and the sense of hearing. The mechanical properties of soft tissues change in middle ear diseases such as otitis media. As a consequence, the mobility of ossicular chain is reduced and significant conductive hearing loss occurs in otitis media ears. However, the mechanical property changes in soft tissue associated with disease are largely unstudied. It is almost impossible to identify mechanical changes of middle ear tissues in relation to hearing loss based on current clinical tools. The goal of this project is to characterize the biomechanical behaviors of soft tissues in normal and diseased ears, identify soft tissue changes which are associated with changes in normal hearing, and provide an improved 3-dimensional (3D) ear model to visualize and quantify structure-function relations in various diseases. Otitis media (OM) will be the primary focus for the project. Three specific aims are proposed: Aim 1: To Identify changes of mechanical properties of middle ear soft tissue in OM. We hypothesize that the change of mechanical properties of ear tissues in OM is related to morphological changes of the tissue in response to fluid, pressure, and duration of the OM. This hypothesis will be tested by comparison of measurement results of the ear tissues between normal and diseased ears in chinchillas using dynamic mechanical analyzer, split Hopkinson tension bar, acoustic driving with laser Doppler vibrometry (LDV), fringe Moiri system, and FE modeling of soft tissue. Aim 2: To quantify the effect of biomechanical changes of the middle ear on sound transmission in OM. It is hypothesized that the hearing loss in OM is caused by a combination of changes of ear tissues, fluid, and pressure in the middle ear. This hypothesis will be tested by measuring the ABR thresholds and the changes of middle ear transfer function and sound energy transmission in chinchilla OM ears with a novel theoretical analysis of fluid, pressure, and tissue properties with the aid of FE model of chinchilla ear to describe the mechanism of OM. Aim 3: To continue the development of our 3D FE model of the human ear with clinically-relevant applications. We will incorporate into the model with tissue properties determined in Aims 1 and 2, the microstructures of the TM and ISJ, and the stapedius muscle function. A FE model of pediatric ear will be created for studying OM in young children. The acoustic-mechanical vibration and energy transmission through the middle ear in diseased ears will be visualized and quantified in the 3D FE model by 4 novel model-derived "auditory test curves", named as: the middle ear transfer function (METF), energy absorbance (EA), admittance tympanogram (AT), and TM holography, which will assist physicians and audiologists to interpret the diagnostic test results and identify the specific type of middle ear disorders. PUBLIC HEALTH RELEVANCE: Middle ear diseases often result in conductive hearing loss due to the changes of middle ear structure and soft tissue properties caused by the diseases. Understanding the relationship between the middle ear structural change and function of the middle ear will help diagnosis of different middle ear diseases. The proposed research project is to determine mechanical property changes in ear tissues associated with middle ear diseases and provide a computational model of the human ear to visualize and quantify structure-function relations in various diseases.