2-photon imaging system

描述(申请人提供)：我们建议购买一种专门用于显微内窥镜检查的双光子配对系统。梯度折射率(GRIN)透镜显微内窥镜允许对以前无法触及的组织进行成像。对于我们的研究核心来说，这意味着对耳蜗进行成像，尽管这并不是排他性的。除了这个系统，我们还需要加入评估听力质量的能力，包括ABR、失真产物耳声发射和鼓室导纳。此外，需要能够进行电生理测量，因此需要微操作器和放大器。这个设备将扩展我们的成像核心，这样整个动物的听力实验就可以在细胞和系统层面上进行。这项技术将使我们前所未有地获得活的耳蜗组织，极大地扩大和加强这一核心内正在进行的研究项目。到目前为止，大多数耳蜗力学测量是在基底膜水平上的单点或双点测量。这项新技术允许对多个细胞或细胞部分进行成像，如感觉发束、覆膜等。主要实验的证据已经与GRIN透镜的顾问和专家(Mark Schnitzer)进行过，但受到限制，因为他们所在的实验室没有声学隔离设备，而且系统也不专门用于这些实验。这种设备有可能彻底改变整个动物的听觉研究，并将扩展我们成像核心的资源，将成像从分子到细胞再到系统。这项技术并不局限于耳蜗探索，正如研究项目部分所展示的那样，可以用来研究活体动物迄今无法接触到的结构，如大脑深部和鼻黏膜细胞。这些项目包括目前由代表五个不同部门的4名调查员资助的6个RO1。此外，目前有三名初级调查人员正在积极研究这项技术。我们核心设施的部分任务是为研究生和住院医生提供准入和培训，因此这项技术的加入将极大地加强培训。此外，这项技术还允许在整个动物身上进行直接的翻译实验。我们有大量的部门支持，为仪器的服务合同、参与设备培训和维护的支持人员以及设备的安装费用提供资金。 与公共健康相关：噪音暴露、老化或化学物质导致的听力损失每年会降低数百万人的生活质量和生产力，给我们的经济造成数十亿美元的损失。长期以来，直接评估化学物质或噪音对感觉组织的作用的能力，一直受到无法接触到耳蜗组织的阻碍，因为它被骨骼包围着。在所需的设备中，使用显微内窥镜的双光子成像系统允许进行微创手术，从而使我们能够直接监测体内的耳蜗组织，从而加快我们对与这些形式的听力损失相关的机制的理解。

DESCRIPTION (provided by applicant): 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.