We are proposing to purchase a two photon mating system that is specialized for microendoscopy. The gradient refractive index (GRIN) lens microendoscope allows for imaging of previously inaccessible tissue. For our research core, this means imaging the cochlea, though this is not exclusive. Along with this system, we need to incorporate the ability to assess quality of hearing, which includes, ABR, distortion product otoacoustic emissions and tympanometry. Additionally, the ability to make electrophysiological measurements is required and so micromanipulators and an amplifier are requested. This device will expand our imaging core so that whole animal hearing experiments can be performed at the cellular and systems level. This technology will give us unprecedented access to living cochlea tissue, greatly expanding and enhancing ongoing research projects within this core. To date, most measurements of cochlea mechanics are single or dual point measurements at the level of the basilar membrane. This new technology allows imaging of multiple cells or cell parts, like sensory hair bundles, tectorial membrane, etc. Proof of principal experiments have been performed with a consultant and expert on GRIN lens (Mark Schnitzer) but are limited by being in a laboratory not equipped for acoustic isolation and on a system that is not dedicated to these experiments. This device has the potential to revolutionize auditory research in the whole animal and will expand the resources of our imaging core to incorporate imaging from the molecular to cellular to system. The technology is not limited to cochlear exploration and as demonstrated in the research projects section can be used to investigate heretofore inaccessible structures in living animals, such as deep brain regions and nasal mucosal cells. Together these projects incorporate 6 presently funded RO1s from 4 investigators representing five different departments. Also there are presently three junior investigators actively pursuing this technology. Part of the mandate of our core facility is to provide access and training to graduate students and residents and so the addition of this technology will greatly enhance training. In addition, this technology allows direct translational experiments to be performed in the whole animal. We have significant departmental support funding the service contract for the instrument, support personnel involved in the training and maintenance of the equipment and the setup costs for the equipment.

Public Health Relevance

Hearing loss induced by noise exposure, aging or chemicals reduce quality of life and productivity of millions of people each year, costing our economy billions of dollars. The ability to directly assess the actions of chemicals or noise on the sensory tissue has long been hampered by the inability to access cochlear tissue, as it is surrounded by bone. The equipment requested, a two photon imaging system using microendoscopy allows minimally invasive surgery to result in our ability to directly monitor cochlea tissue in vivo and thus will expedite our understanding of the mechanisms associated with these forms of hearing loss.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1-SBIB-A (30))
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Levy, Abraham
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Stanford University
Schools of Medicine
United States
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Soons, Joris A M; Ricci, Anthony J; Steele, Charles R et al. (2015) Cytoarchitecture of the mouse organ of corti from base to apex, determined using in situ two-photon imaging. J Assoc Res Otolaryngol 16:47-66