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.
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.
|Warren, Rebecca L; Ramamoorthy, Sripriya; CiganoviÄ‡, Nikola et al. (2016) Minimal basilar membrane motion in low-frequency hearing. Proc Natl Acad Sci U S A 113:E4304-10|
|Ramamoorthy, Sripriya; Zha, Dingjun; Chen, Fangyi et al. (2014) Filtering of acoustic signals within the hearing organ. J Neurosci 34:9051-8|
|Subhash, Hrebesh M; Choudhury, Niloy; Chen, Fangyi et al. (2013) Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry. J Biomed Opt 18:036003|
|Ramamoorthy, Sripriya; Nuttall, Alfred L (2012) Outer hair cell somatic electromotility in vivo and power transfer to the organ of Corti. Biophys J 102:388-98|
|Zha, Dingjun; Chen, Fangyi; Ramamoorthy, Sripriya et al. (2012) In vivo outer hair cell length changes expose the active process in the cochlea. PLoS One 7:e32757|
|Subhash, Hrebesh M; Nguyen-Huynh, Anh; Wang, Ruikang K et al. (2012) Feasibility of spectral-domain phase-sensitive optical coherence tomography for middle ear vibrometry. J Biomed Opt 17:060505|
|Subhash, Hrebesh M; Davila, Viviana; Sun, Hai et al. (2011) Volumetric in vivo imaging of microvascular perfusion within the intact cochlea in mice using ultra-high sensitive optical microangiography. IEEE Trans Med Imaging 30:224-30|
|Chen, Fangyi; Zha, Dingjun; Fridberger, Anders et al. (2011) A differentially amplified motion in the ear for near-threshold sound detection. Nat Neurosci 14:770-4|
|Wang, Ruikang K; Nuttall, Alfred L (2010) Phase-sensitive optical coherence tomography imaging of the tissue motion within the organ of Corti at a subnanometer scale: a preliminary study. J Biomed Opt 15:056005|
|Subhash, Hrebesh M; Davila, Viviana; Sun, Hai et al. (2010) Volumetric in vivo imaging of intracochlear microstructures in mice by high-speed spectral domain optical coherence tomography. J Biomed Opt 15:036024|