ANIMAL VALIDATION OF A NEW VOLUME SENSOR FOR FEEDBACK TREATMENT OF HYDROCEPHALUS

描述(由申请人提供)：脑积水是一种疾病，每年影响1000名新生儿中的一名，或7万名患者。在美国，分流翻修的治疗费用每年高达10亿美元。尽管脑积水很重要，但其治疗仍缺乏改进。根据我们小组在颅内动力学方面的最新发现，以及先前获得NIH R-21拨款的新阻抗容量测量的原理证明，以及准备这项提案的全面前期工作，我们对改进脑积水治疗方案的可能性充满信心。我们的论点是，需要一种新的方法来适当地维持儿童和成人脑积水。在这项建议中，我们希望在小型和大型脑积水动物身上测试一种新型的阻抗体积传感器。该项目的总体愿景旨在改进基于体积感知和主动反馈的脑积水治疗。为了实现这一愿景，我们提出了以下三个具体目标：目的1.慢性植入大鼠脑积水模型。我们提出了诱导幼年大鼠脑积水的方法。动态容量测量将使用微型老鼠微型传感器进行，持续时间长达30天。脑室的核磁共振扫描将独立验证传感器的准确性。从老鼠实验中获得的经验将被纳入狗的模型中。目的#2.杂种犬的颅内容量和压力监测。传感器将被调整以用于慢性狗实验。传感器、仪器和数据采集将被植入少数脑积水动物体内。微型机电压力传感器将在测量心室容量的同时获得动态压力。据我们所知，发生在脑积水中的实时压力和容量变化从未被同时监测过。目标#3.人体监控系统的计算机辅助设计。我们将把动物实验结果纳入用于人类治疗的计算机辅助设计中。我们将模拟脑积水中的脑室扩张，以确定适合人类系统的最佳传感器参数。对具有主动反馈控制分流的传感器性能进行了仿真。这项研究将展示一种基于主动反馈控制的新型体积测量的新型治疗系统的参数和预期性能。 公共卫生相关性：这个跨学科项目的关键思想是为脑积水动物制造一种新型的基于阻抗的脑室容量传感器。微制造技术将与先进的医学成像和科学计算方法相结合，设计出具有最佳精度和灵敏度的新型传感器。该传感器将在一系列老鼠实验中进行测试。传感器和仪器将被定标为可植入的脑室大小监测器，用于杂种犬脑积水模型。通过测量诱发脑积水过程中的脑室扩张所获得的新知识将被用于设计人类的监测和控制系统。基础知识的增长将为积极的容量感知和反馈的脑积水的新治疗选择铺平道路。

DESCRIPTION (provided by applicant): Hydrocephalus is a disease affecting one in 1,000 births, or 70,000 patients a year. Treatment cost in the U.S. for shunt revision amount to one billion dollars every year. Despite the significance of hydrocephalus, there is a lack of improvement for its treatment. Based on recent findings of our group in intracranial dynamics, proof-of- principle of a new impedance volume measurement with a prior NIH R-21 grant and comprehensive preliminary work in preparation of this proposal, we have confidence in the possibility of improving hydrocephalus treatment options. Our contention is that a new approach is necessary for proper maintenance of childhood and adult hydrocephalus. In this proposal, we wish to test a novel impedance volume sensor in small and large hydrocephalic animals. The overall vision of the project aims at improving hydrocephalus therapy based on volume sensing combined with active feedback. To realize this vision, we propose the following three specific aims: Aim #1. Chronic implantation into rat hydrocephalic model. We propose to induce hydrocephalus in juvenile rats. Dynamic volume measurements will be made with a miniaturized rat micro-sensor for a period of up to 30 days. MRI scans of the ventricles will independently verify sensor accuracy. The experience gained from rat experiments will be incorporated into a dog model. Aim #2. Intracranial volume and pressure monitoring in mongrel dogs. Sensors will be scaled for chronic dog experiments. Sensor, instrumentation and data acquisition will be implanted into a small number of hydrocephalic animals. Micro-electromechanical pressure transducers will be incorporated to acquire dynamic pressure alongside ventricular volume measurements. Real-time pressure and volume changes occurring in hydrocephalus have never been monitored simultaneously to the best of our knowledge. Aim #3. Computer-aided design of a human monitoring and control system. We will incorporate animal results into a computer-aided design for a human therapy. We will simulate ventricular expansion in hydrocephalus to determine the optimal sensor parameters for a human system. Sensor performance with an active feedback control shunting will be simulated. The proposed research will lay out the parameters and expected performance of a novel treatment system based on the novel volume measurement with active feedback control. PUBLIC HEALTH RELEVANCE: The key idea in this interdisciplinary project is to manufacture a novel impedance-based ventricular volume sensor for hydrocephalic animals. Microfabrication techniques will be used in combination with advanced medical imaging and scientific computing methods to design a novel sensor with optimal accuracy and sensitivity. The senor will be tested in a series of rat experiments. The sensor and instrumentation will be scaled for an implantable ventricular size monitor for a mongrel dog hydrocephalus model. New knowledge obtained from measuring the ventricular expansion in the course of induced hydrocephalus will be used to designing a monitoring and control systems for humans. The fundamental knowledge gain will pave the way for novel treatment options of hydrocephalus with active volume sensing and feedback.