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

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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.