Pediatric Percutaneous Cochlear Implantation Clinical Validation & Implementation

描述（由申请人提供）：耳蜗植入（CI）手术目前需要进入内耳，特别是耳蜗，其中电极阵列用于刺激听觉神经并允许聋人听到。在全球范围内已经放置了超过120，000个CI。预测表明，多达750，000名患有严重听力损失的美国人可能受益于CI（Mohr，Feldman，Dunbar等人，2000年，其中许多人是儿童。在我们正在进行的NIH资助的成人项目（R 01 DC 008408）中，我们已经证明了经皮耳蜗植入（PCI）的可行性。PCI将CI手术减少为从侧颅底到耳蜗的单次钻孔。通过图像引导技术规划和执行钻孔路径，以避开重要的邻近解剖结构并击中目标耳蜗的鼓阶。在临床试验中，我们已经验证了15例成人患者的统计预测表明99.9%的避免重要解剖结构，特别是面神经的技术。在随附的提交资料中，我们建议将该技术应用于儿科人群。要做到这一点，我们的技术修改是必要的。我们目前的成人技术包括以下六个步骤：（i）在门诊环境中在局部麻醉下将三个骨植入的基准标记/锚围绕耳朵放置，（ii）获得临床上可应用的CT扫描，（iii）使用CT扫描来规划从颅骨表面到耳蜗的基底圈的手术轨迹，避免重要解剖结构，（iv）构建微立体定向框架以约束钻头沿计划轨迹沿着通过（对于成人研究，框架构建需要48小时），（v）将框架固定到骨植入锚，以及（vi）使用框架来确认钻头轨迹。由于儿童和成人在解剖学上不同，我们建议通过使用儿科CT扫描的大型数据库来修改我们的技术，以产生年龄分层的解剖图谱，这将使我们能够以自动化的方式执行步骤（iii），就像我们目前为成人使用单个图谱所做的那样。由于联邦指南禁止对儿童进行风险大于最小风险且无儿童受益前景的临床研究，因此我们对步骤（ii）和（iv）进行了实质性修改，使得CT扫描的采集以及微立体定向框架的设计和构建与传统CI手术同时进行，从而将风险降低至指南规定的可接受水平。为此，我们做了大量工作，将术中CT扫描仪纳入我们的方案，并设计、开发和测试了一种新型的微立体定向框架，该框架可以在30分钟内设计和构建，远低于我们对2，256例手术的回顾中的最短手术时间。我们已经招募了另外两个备受尊敬的CI项目参与研究-男孩城（奥马哈，NE）和世界上最繁忙的CI中心，汉诺威医学医院（汉诺威，德国），我们与他们有长期的合作。我们希望这种经皮人工耳蜗植入技术能够使CI手术更快，更便宜，更容易执行，让更多的儿童受益于CI的听力康复。 公共卫生相关性：在美国，大约有20，000名失聪儿童受益于人工耳蜗植入术，这是一个2小时以上的手术，涉及切除外耳后面的一部分骨头以到达内耳，耳蜗，并放置一根刺激耳蜗的电线，从而允许听力。使用图像引导手术技术-类似于用于提供地理方向的GPS技术-我们已经证明，通过跟踪和控制钻头的路径，使得耳蜗可以通过单个钻头到达，可以实现侵入性更小的手术方法-我们称这种技术为经皮耳蜗植入术（PCI），并已在成人患者中进行了证明。我们现在建议在儿童中测试和进行PCI，我们的努力集中在成人和儿童之间的差异（例如，（i）解剖结构和（ii）管理研究的联邦法规），PCI的拟议益处包括缩短手术时间，降低手术成本，标准化手术，甚至可能改善听力结果。

DESCRIPTION (provided by applicant): Access to the inner ear, specifically the cochlea, is currently required for cochlear implant (CI) surgery, in which an electrode array is used to stimulate the auditory nerve and allow deaf people to hear. More than 120,000 CIs have been placed worldwide. Projections indicate that up to 750,000 Americans with severe hearing loss may benefit from CI (Mohr, Feldman, Dunbar et al., 2000) many of whom are children. In our ongoing, NIH-funded adult project (R01 DC008408), we have demonstrated the feasibility of percutaneous cochlear implantation (PCI). PCI reduces CI surgery to a single pass of a drill from the lateral skull base to the cochlea. The drill path is planned and executed via image-guided technology so as to avoid vital adjacent anatomy and hit the target-the scala tympani of the cochlea. In clinical trials we have validated the technique on 15 adult patients with statistical projections indicating 99.9% avoidance of vital anatomy, specifically the facial nerve. In the attached submission, we propose to translate this technology to the pediatric population. To do this, modifications to our technique are necessary. Our current adult technique consists of the following six steps: (i) placing three bone-implanted fiducial markers/anchors surrounding the ear under local anesthesia in an out-patient setting, (ii) obtaining a clinically applicable CT scan, (iii) using the CT scan to plan a surgical trajectory from the surface of the skull to the basal turn of the cochlea avoiding vital anatomy, (iv) constructing a microstereotactic frame to constrain a drill to pass along the planned trajectory (for the adult study, frame construction requires 48 hours), (v) affixing the frame to the bone-implanted anchors, and (vi) employing the frame to confirm the drill trajectory. Because children and adults differ anatomically, we propose to modify our technique by using a large database of pediatric CT scans to produce age-stratified anatomical atlases that will allow us to perform step (iii) in an automated fashion, as we are currently doing for adults with a single atlas. Because federal guidelines prohibit clinical studies on children entailing greater than minimal risk without the prospect of benefit for children, we have substantially modified steps (ii) and (iv) such that both the acquisition of the CT scan and the design and construction of the microstereotactic frame occur simultaneously with traditional CI surgery, thus reducing the risk to an acceptable level under the guidelines. To do this, we have done extensive work incorporating intraoperative CT scanner into our protocols and designed, developed, and tested a novel microstereotactic frame which can be designed and constructed in 30 minutes-well below the shortest surgical time in our review of 2,256 surgeries. We have recruited two additional well-respected CI programs to participate in the study-Boys Town (Omaha, NE) and the busiest CI center in the world, Medical Hospital of Hannover (Hannover, Germany) with whom we have a standing collaboration. Our hope is that this technique, percutaneous cochlear implantation, will make CI surgery quicker, cheaper, and easier to perform, allowing more children to benefit from aural rehabilitation with CIs. PUBLIC HEALTH RELEVANCE: In the United States about 20,000 deaf children have benefitted from cochlear implantation, a 2+ hour surgery that involves removal of a portion of the bone behind the external ear to reach the inner ear, the cochlea, and place a wire which stimulates the cochlea allowing hearing. Using image guided surgical techniques-similar to GPS technology used to provide geographic directions-we have shown that a much less invasive surgical approach is possible by tracking and controlling the path of a drill such that the cochlea may be reached by a single drill-we call this technique Percutaneous Cochlear Implantation (PCI) and have demonstrated it in adult patients. We now propose to test and perform PCI in children with our efforts focused on the differences between adults and children (for example, (i) anatomy and (ii) federal regulations governing research) with the proposed benefits of PCI including decreased operative time, decreased surgical cost, standardized surgery, and possibly even improved hearing outcomes.