Human middle-ear imaging, physiology, and biomechanics

描述（申请人提供）：中耳在听觉的感觉和灵敏度中起着至关重要的作用，但目前对哺乳动物中耳高频声音传输的机制还缺乏了解。该项目的总体目标是了解中耳形态与导致生理和临床反应的生物力学过程之间的关系。该方法是将中耳分解为子系统，每个子系统都具有形态和生理测量的特征，以及三维线性和非线性数学分析。然后，这些子系统在数学上重新组合，形成一个完整的“虚拟中耳”模型，可用于检查与各种动物的高频声音传输相关的问题，并在手术前后修复中耳。具体目标1：在高频率下，实验证据表明，声音传导不受中耳骨惯性的限制，这与预期相反。最近的惯性矩计算表明，锤骨从低频的铰接运动切换到高频的新的扭转运动，以利用与扭转运动相关的减少的惯性。据推测，活动的鞍状锤骨-砧骨关节能够适当地将这种扭转运动转移到砧骨上。这将使用微型ct成像、低温透射电子显微镜、光学二次谐波产生、激光多普勒振动计的铰链和扭转运动测量以及生物计算模型进行测试。针对性# 2:人类的中耳腔是一个形状不规则的空间在颞骨,因人而异。有限元建模方法将被用来测试的假设人类的中耳腔的复杂形状函数分解谐振模式,否则听力灵敏度在特定的共振频率降低。有限元方法非常适合于将鼓室张量和镫骨肌施加的力结合起来的非线性描述，也将用于了解这些肌肉如何影响中耳的声音传输。具体目标3：耳外科医生的目标是恢复语音频率范围内的听力，而不是在已知的重要声音定位线索所在的更高频率。颞骨测量和基于解剖学和物理学的虚拟中耳模型将用于了解如何改善中耳手术治疗的高频结果，例如鼓膜修复（鼓膜成形术）和听骨假体置换（鼓膜成形术）。具体目标4：我们的假设是，鼓膜成形术和鼓室成形术患者在频率高于4khz时仍然存在气骨间隙缺损，我们将对这一假设进行测试。测量骨传导灵敏度的新方法将用于高频，并与现有的空气传导测量方法相结合。虽然人们普遍认为，在陆生脊椎动物中，哺乳动物的中耳在将外部世界的声音传输到耳蜗的频率高于10千赫的能力上是独一无二的，但人们对高频声音传输的生物力学基础知之甚少，这在临床领域产生了影响。众所周知,中耳的形态测量学在声音传播起着关键的作用,但缺乏知识的中耳结构之间的关系和声音传播导致不满意的和可变的结果中耳维修,尤其是在高频率声音定位信号可能是重要的听力在嘈杂的情况下。本研究将为了解中耳声音传输的结构基础提供坚实的科学基础，为中耳外科重建的临床应用、耳声发射的解释以及提高外科医生对中耳修复所使用的被动和主动假体的理解提供依据。

DESCRIPTION (provided by applicant): The middle ear plays a vital role in the sense and sensitivity of hearing, yet there is currently a lack of knowledge about the mechanisms of high-frequency middle-ear sound transmission in mammals. The overall goal of this project is to understand the relationships between the morphometry of the middle ear and the biomechanical processes that lead to physiological and clinical responses. The approach is to deconstruct the middle ear into subsystems that are each characterized by morphological and physiological measurements, as well as three-dimensional linear and nonlinear mathematical analyses. The subsystems are then mathematically reassembled to form a complete `virtual middle-ear' model that can be used to examine issues relevant to high frequency sound transmission in a variety of animals and repaired middle ears before and after surgery. Specific Aim #1: At high frequencies, experimental evidence suggests that sound conduction is not limited by the inertia of the middle-ear bones, contrary to expectations. Recent moment of inertia calculations suggest that the malleus switches from a hinging motion at low frequencies to a new twisting motion at high frequencies, in order to take advantage of the reduced inertia associated with a twisting type of motion. It is hypothesized that the mobile saddle-shaped malleus-incus joint is able to suitably transfer this twisting motion to the incus. This will be tested using micro-CT imaging, cryogenic transmission electron microscopy, optical second harmonic generation, hinging and twisting motion measurements with a laser Doppler vibrometer, and bio-computational modeling. Specific Aim #2: The human middle-ear cavity is known to be an irregularly shaped space within the temporal bone that varies from person to person. A finite element modeling approach will be used to test the hypothesis that the complex shape of the human middle-ear cavity functions to break up resonant modes that would otherwise decrease hearing sensitivity at specific resonant frequencies. The finite element approach, which is well-suited for the nonlinear descriptions needed to incorporate the forces exerted by the tensor tympani and the stapedius muscles, will also be used to understand how these muscles affect sound transmission through the middle ear. Specific Aim #3: Ear surgeons target restoration of hearing in the speech frequency range, and not in the higher frequencies where important sound localization cues are known to reside. Temporal bone measurements and the anatomically- and physics-based virtual middle-ear model will be used to understand how to improve high-frequency outcomes of middle-ear surgical treatments, such as tympanic membrane repair (myringoplasty) and ossicle replacement with a prosthesis (tympanoplasty). Specific Aim #4: Our hypothesis that myringoplasty and tympanoplasty surgery patients continue to have air-bone gap deficits at frequencies above 4 kHz will be tested. New methods to measure bone conduction sensitivity will be developed for high frequencies and combined with existing air conduction measurement methods. While it is well accepted that amongst terrestrial vertebrates, the mammalian middle ear is unique in its ability to transmit sounds from the external world to the cochlea for frequencies above 10 kHz, the biomechanical basis for sound transmission at high frequencies is poorly understood, which has consequences in the clinical realm. It is well known that the morphometry of the middle ear plays a key role in sound transmission, but the lack of knowledge about the relationships between middle-ear structures and sound transmission has resulted in unsatisfactory and variable outcomes of middle-ear repairs, particularly at high frequencies where sound localization cues may be important for hearing in noisy situations. The proposed studies will provide a solid scientific foundation for understanding the structural basis of middle-ear sound transmission, leading to clinical applications for the surgical reconstruction of the middle ear, the interpretation of otoacoustic emissions, and improvements to the understanding of passive and active prostheses used by surgeons to repair the middle ear.