Hydrocephalus is a common condition caused by the accumulation of cerebrospinal fluid (CSF) in the brain, with symptoms that include headaches, lethargy, seizures, coma, or death, and affects > 1 million patients in the United States. It is usually treated with the surgical implantation of a catheter, known as a ventricular shunt, which diverts the excess CSF in the brain to a distal absorptive site. Overall, 125,000 shunts are implanted or replaced annually in United States, with costs estimated at $2 billion per year. We have identified two unmet needs in hydrocephalus diagnostics: (i) precise, rapid, noninvasive way to monitor shunt function; (ii) a large gap in clinical knowledge of CSF hydrodynamics through shunts owing to a lack of a direct, continuous flow monitoring technology. To address this need, Rhaeos has developed the first wearable, wireless sensor for CSF flow monitoring. Our first platform, Flow Sense, exploits miniaturized thermal sensors and actuators to map thermal transport through the skin as a measure of subdermal fluid flow to make rapid spot checks to address the first challenge outlined above. Expanding these capabilities to include continuous monitoring, 24-hour of CSF flow, particularly during periods of sleep, would benefit the treatment, care and understanding of hydrocephalus. We hypothesize that continuous measurements will provide and allow for robust out-patient monitoring and enhancing in-patient monitoring capabilities, particularly in emergency departments. The resulting technology, if successful, could reduce unnecessary hospital admissions and lower in- patient stay periods by allowing for direct monitoring in patient homes. Additionally, understanding CSF hydrodynamics during sleep will be valuable in enhancing a basic scientific understanding of hydrocephalus and the glymphatic system. To address the goal, we will develop the first sensor capable of continuous, 24-hour CSF flow measurements. In the UG3 phase we will modify our hardware and software platform for safety, comfort, robustness, and usability for continuous, uninterrupted wear at home. Additionally, we will undertake DFMEA and design for manufacturability efforts in compliance with an FDA- and ISO13485 compliant quality management system. The completion and successful outsourced manufacturing run of a sensor capable of continuous use over 1 week will form the core of a set of go/no go milestones to transition to the clinical UH3 phase. In the UH3 phase, we will conduct a 1-week double-arm, single-center, blinded, longitudinal clinical study with historically stable shunt patients and patients with recent shunt revisions.

Long-term cerebrospinal fluid dynamics in patients with shunted hydrocephalus during sleep and while performing activities of daily living (ADL) are clinically and scientifically important to identify and diagnose shunt failure, identify underlying causes, and evaluate the success of surgical revision procedures. However, they remain largely unknown owing to a lack of a direct monitoring technology to noninvasively measure flow through shunts, especially through periods of sleep. In this proposal, Rhaeos will undertake quality-controlled product development (UG3 phase) of the first sensor capable of continuous flow measurements over extended periods (~1 week) in remote monitoring settings, followed by a n = 20 patient NSR-feasibility study (UH3 phase) to evaluate device performance and safety.