PROJECT SUMMARY/ABSTRACT Changes to cerebral spinal fluid flow (CSF) dynamics may occur with traumatic brain injury, subarachnoid and/or intraventricular hemorrhage, brain neoplasms, or central nervous system infection, and can all lead to increased intracranial pressure (ICP). Neurosurgeons treat elevated ICP by placing a ventricular shunt, which allows excess CSF to drain, thereby relieving the pressure on the brain. Over 50% of shunts fail in the first year, and all shunts fail eventually. Shunt failure most commonly occurs in children under the age of 1 year and accounts for over $1 billion in hospital admission costs. Unfortunately, verifying that a patient has a shunt dysfunction is particularly difficult in young patients, as symptoms are non-specific (headache, nausea, or fatigue) and existing non-invasive tests (MRI and CT) are costly and do not directly measure pressure. Only 46% of shunt patients presenting with these symptoms have a dysfunction, while the remaining patients incur unnecessary expense, exposure to radiation, or invasive investigations that may result in brain injury. To address this issue, we propose to create iPPSIS (implanted Passive Pressure Sensors Interrogated with (ultra) Sound), which is composed of a passive, microfabricated pressure sensor “target” that deflects in response to increased pressure and can be quantitatively measured with ultrasound. We hypothesized that rethinking the current approach to wireless pressure sensors and removing the dependence on RF telemetry would lead to a wireless sensor that is passive (no batteries), MRI compatible, and stable for long-term clinical monitoring (years). As requested in the FOA, no unpublished preliminary data is included. However, our analytical calculations of both the microfabricated target design and ultrasound resolution, which are grounded in decades of research, demonstrate feasibility and a high probability of success. We will initially design iPPSIS for pediatric populations given the significant need and lower technical barriers due to the reduced skull thickness. The sensor will be implanted subdurally through a standard burr hole during a shunt placement procedure, and will continue to operate as the patient's skull heals and reforms. Aim 1 focuses on the construction and characterization of a novel, extremely stable, metallic micro-pressure sensor that will be highly impervious to the physiological “harsh environment”. Aim 2 focuses on the testing of a novel operator- independent ultrasound measurements and a new wearable ultrasonic transducer that would enable long-term continuous monitoring. Aim 3 seeks to rigorously test iPPSIS in vitro as well collect in vivo feasibility data in a porcine tumor model (n=2) that experiences rapid ICP changes over several months. Attesting to the rigor of our approach, we have assembled a team of individuals with expertise spanning micro-electro-mechanical systems design, ultrasound, neurosurgery, and in vivo porcin...