Understanding cochlear pathophysiology and function using picometer sensitive, spatially resolved vibrometry in the ear

In humans, many of the diagnoses for hearing loss and vertigo or disequilibrium are based on a process of elimination, rather than positive proof of a particular pathology. This is especially true for diseases of the inner ear, which can lead to misdiagnosis and improper treatment. Diseases of the inner ear while not life threatening can have a profound impact on the patient’s quality of life. Hearing loss due to all causes affects over 30 million Americans. Conclusive diagnosis of the cause of hearing loss is not possible in most cases due to our inability to interrogate the soft tissues of the inner ear responsible for hearing. In fact, there is a fundamental lack of imaging technology capable of in vivo investigation of morphological and functional changes in the soft tissues of the inner ear of humans or animal models. This stems from the fact that inner ear in mammals is located deep inside the bone of the skull, the temporal bone in humans. 

Our work in this area is aimed at filling this void for both human patients and animal models of hearing disease. Our approach is fundamentally based on Optical Coherence Tomography (OCT), a medical imaging technique used clinically for imaging the eye, coronary arteries, and esophagus. Our system development for animal imaging has focused on achieving extremely high sensitivity to vibration (~10 pm) at high imaging speeds using a fixture attached to a normal dissecting stereomicroscope. Recent results include the first measures of tectorial membrane vibration within the unopened cochlea.  For humans we are developing specialized systems that will enable imaging during surgery and  awake patients in the clinic. This work is being done in collaboration with our collegues  at Stanford University Department of Otolaryngology/Head and Neck Surgery.

OCT image of a live mouse cochlea. The otic capsule (bone) has been segmented and slowly recedes to reveal the underlying soft tissues of the cochlea in this volume rendering.

OCT image of a live mouse cochlea. The otic capsule (bone) has been segmented and slowly recedes to reveal the underlying soft tissues of the cochlea in this volume rendering.


Relevant Publications

  1. A. Xia, X. Liu, P. D. Raphael, B. E. Applegate, and J. S. Oghalai, “Hair cell force generation does not amplify or tune vibrations within the chicken basilar papilla,” Nature Comm., 7, 13133 (2016) PMID:27796310
  2. H. Y. Lee, P. D. Raphael, J. Park, A. K. Ellerbee, B. E. Applegate, and J. S. Oghalai, “Traveling wave propagation measured within tissue using volumetric optical coherence tomography vibrometry,” Proc Natl Acad Sci USA, 112, 3128-3133, (2015) PMID:25737536 
  3. J. Park, E. F. Carbajal, X. Chen, J. S. Oghalai, and B. E. Applegate, “Phase-sensitive optical coherence tomography using a Vernier-tuned distributed Bragg reflector swept laser in the mouse middle ear,” Opt. Lett., 39, 6233-6236, (2014)  PMID: 25361322
  4. S. S. Gao, R. Wang, P. D. Raphael, Y. Moayedi, A. K. Groves, J. Zuo, B. E. Applegate, and J. S. Oghalai, "Vibration of the organ of Corti within the cochlear apex in mice," J Neurophysiol (2014) PMID: 24920025    
  5. S. S. Gao, P. D. Raphael, R. Wang, J. Park, A. Xia, B. E. Applegate, and J. S. Oghalai, "In vivo vibrometry inside the apex of the mouse cochlea using spectral domain optical coherence tomography," Biomed Opt Express 4, 230-240 (2013) PMID: 23411442   
  6. B. E. Applegate, R. L. Shelton, S. S. Gao, and J. S. Oghalai, "Imaging high-frequency periodic motion in the mouse ear with coherently interleaved optical coherence tomography," Opt Lett 36, 4716-4718 (2011) PMID: 22139294    
  7. S. S. Gao, A. Xia, T. Yuan, P. D. Raphael, R. L. Shelton*, B. E. Applegate, and J. S. Oghalai, "Quantitative imaging of cochlear soft tissues in wild-type and hearing-impaired transgenic mice by spectral domain optical coherence tomography," Opt Express 19, 15415-15428 (2011) PMID: 21934905