Tomographic Imaging of Cochlear Micromechanical Motions

描述(申请人提供)：耳蜗是一种非凡的传感器：活的耳蜗可以可靠地检测到引起皮米数量级的距骨运动的声音，能够进行高质量的频谱分析(Q10dB&gt；600)，并将听力的大动态范围(120分贝)压缩到相当小的神经元动态范围(20-50分贝)。现在人们普遍认为，活跃的机械放大过程是这些显著特性的基础。然而，关于放大器的性质仍有相当大的争议。虽然关于听力的细胞和分子基础的信息正在迅速增加，但对于这些组件如何相互作用来产生听力的显著特性，人们仍然知之甚少。 到目前为止，对活体耳蜗细胞运动的最成功的实验研究是使用光学方法。然而，目前的方法，如激光多普勒测振仪和视频显微镜，由于耳蜗结构的低反射率和由完整的耳蜗所提供的有限的光学通路而受到限制。这项赠款的目标是开发和应用一种新的断层成像和运动测量技术，能够确定活的完整耳蜗中所有结构的三维运动。光学相干断层扫描(OCT)将被用来获得高分辨率的耳蜗图像。图像将通过一个类似于激光多普勒测振方法中使用的狭窄开口来获取，或者可能直接通过骨骼。在声刺激期间，将通过OCT探测器信号的同步解调来生成频闪图像序列。计算机视觉算法(类似于视频显微镜方法中使用的算法)将用于确定纳米分辨率的运动。这项技术将被应用于成像和测量完整耳蜗内部微结构的三维运动，包括基底膜、网状板、覆盖膜和外毛细胞。

DESCRIPTION (provided by applicant): The cochlea is a remarkable sensor: a living cochlea can reliably detect sounds that cause motions of the stapes on the order of picometers, is capable of high-quality frequency analysis (Q10dB > 600), and compresses the large dynamic range (120 dB) of hearing into the considerably smaller dynamic range (20- 50 dB) of neurons. It is now widely accepted that an active mechanical amplification process underlies these remarkable properties. However, there is considerable debate about the nature of the amplifier. While information on the cellular and molecular basis of hearing is increasing rapidly, there is still little understanding of how the components interoperate to generate the remarkable properties of hearing. To date, the most successful experimental studies of cellular motions in living cochleae have used optical methods. However, current methods, such as laser Doppler vibrometry and video microscopy are limited by the low reflectivities of cochlear structures and the limited optical access provided by the intact cochea. The objective of this grant is to develop and apply a new tomographic imaging and motion measurement technique capable of determining the three-dimensional motions of all structures in a living, intact cochlea. Optical coherence tomography (OCT) will be used to obtain high-resolution images of the cochlea. Images will be acquired through a narrow opening similar to that used in laser Doppler vibrometry methods, or possibly directly through bone. Sequences of stroboscopic images will be generated with synchronous demodulation of the OCT detector signal during acoustic stimulation. Computer vision algorithms (similar to those used in video microscopy methods) will be used to determine motions with nanometer resolution. This technique will be applied to image and measure three-dimensional motions of the internal microstructure of an intact cochlea, including the basilar membrane, reticular lamina, tectorial membrane, and outer hair cells.