3-D optical imaging of the in vivo organ of Corti motion at a sub-nanometer scale

描述(申请人提供)：低光相干断层扫描(OCT)已被用于对生物组织成像，并且是商业上可用于成像人眼的晶状体和细胞结构的显微镜的理论基础。基于OCT的干涉仪还没有生产出来，但具有独特的特性，可用于内耳组织和细胞的振动测量。我们建议开发一种OCT干涉仪，它既能为活的Corti器官成像，又能测量其细胞在3维空间的运动，振动小至0.1 nm。OCT干涉测量的基本概念已经被证明对Corti器官的微观力学是有用的。这一提议实现了技术进步，从而实现了所需的更高分辨率，从而能够在细胞一级确定器官移位矢量的方向和相位。通过使用飞秒脉冲激光，该仪器将具有约3立方微米的成像和振动分辨率。这是通过结合一种新的相敏OCT方法来实现的，该方法允许使用该仪器来测试覆盖膜在横向(径向)上机械共振的假设。对覆膜体内机制的了解，包括共振，将打消四分之一个世纪以来关于器官如何实现内耳毛细胞立体纤毛的有效机械刺激以及随后哺乳动物听力的非凡敏感性的猜测。 公共卫生相关性：这种光学相干断层扫描(OCT)仪器将允许的耳蜗力学发现对于理解正常听力、用作临床测听测试的耳声发射的机制以及由响声和耳聋基因导致的听力缺陷至关重要。我们将开发的OCT方法在耳鼻咽喉科也有其他对人类健康的应用：OCT可以成像中耳结构的振动作为听力测量方法，测量人类内耳的血流以区分哪些突发性耳聋患者血流不足或测量和映射微血管皮瓣中的血流以提高皮瓣的存活率。

DESCRIPTION (provided by applicant): Low optical coherence tomography (OCT) has been used to image biological tissue and is the theoretical basis of microscopes that are commercially available to image the lens and cellular structures of the human eye. Interferometers based on OCT have not been produced but have unique properties useful for vibration measurements of the tissues and cells of the inner ear. We propose to develop an OCT interferometer that has the ability to both image the living organ of Corti and measure its cellular motion in 3-dimensions down to a vibration as small as 0.1 nm. The basic concept of OCT interferometry has already proven usefulness for the micromechanics of the organ of Corti. This proposal implements technical advances that permit needed higher resolution that enables determination of the direction and phase of the organ displacement vector at the cellular level. The instrument will have an imaging and vibration resolution of about 3 cubic micrometers through the use of a femtosecond pulsed laser. This is accomplished by incorporation of a novel phase-sensitive OCT approach allowing the instrument to be used to test the hypothesis that the tectorial membrane is mechanically resonant in the lateral (radial) direction. Knowledge of the in vivo mechanics of the tectorial membrane, including resonance, will set to rest a quarter century of conjecture on how the organ achieves the efficient mechanical stimulation of the inner ear hair cell stereocilia and the subsequent remarkable sensitivity of mammalian hearing. PUBLIC HEALTH RELEVANCE: The discoveries of cochlear mechanics that this optical coherence tomography (OCT) instrument will allow are critical to the understanding of normal hearing, the mechanisms of the otoacoustic emissions that are used as clinical audiometric tests and the defects in hearing caused by loud sound and by deafness genes. The OCT method we will develop also has other applications for human health in Otolaryngology: OCT could image the vibration of the middle ear structures as an audiometric method, measure blood flow in the human inner ear to classify which patients with sudden deafness have deficient flow or measure and map blood flow in a microvascular skin flap to improve the viability of flaps.