DESCRIPTION (provided by applicant): This Phase 1 SBIR will develop a portable, non-invasive tool which will improve the diagnostic accuracy of kinetic shunt patency testing, including radionuclide studies or ShuntCheck tests, in pediatric hydrocephalus patients. This will improve clinical care for pediatric hydrocephalus patients with suspect shunt malfunction. Hydrocephalus is a common condition in which CSF accumulates in the brain ventricles, potentially leading to brain damage and death. It is corrected by placing a VP shunt that carries excess CSF away. Although enormously successful, shunts eventually fail, usually by obstruction. However, the clinical symptoms of shunt obstruction, primarily including headache and nausea, are non-specific, making shunt failure challenging to diagnose. Suspected obstruction is typically investigated using static MRI and CT scans which are expensive, and require evidence of fluid accumulation in serial images, precluding prediction of shunt failure. Exposure to radiation is also significant in shunted children, who may require several shunt investigations annually. Radionuclide studies, which provide dynamic measures of shunt CSF flow, are invasive and carry the risk of infection. They also have reduced diagnostic specificity due to intermittent shunt flow - patent shunts do not flow continuously leading to a high level of false positive readings. A new, non-invasive test for shunt flow, ShuntCheck, also suffers from reduced specificity due to intermittent shunt flow. There are currently no tools for differentiating between intermittently flowing patent shunts and occluded shunts. NeuroDx Development (NeuroDx) has recently developed and bench tested a tool which generates a reproducible level of CSF flow through patent shunts. Used in conjunction with radionuclide studies or ShuntCheck testing, this new device can improve diagnostic specificity of both test methods. The NeuroDx "Micro-Pumper" is a small device which is held against the shunt valve during the radionuclide or ShuntCheck test. The device provides specific vibration pulses to the valve, creating a controlled level of CSF flow through the valve. Using a bench model of CSF flow, we have shown that the Micro-Pumper, used in combination with ShuntCheck can differentiate between non-flowing patent shunts and occluded or partially occluded shunts. The goal of this Phase 1 project is to extend these preliminary findings to develop a clinic-ready prototype Micro-Pumper device and to verify its ability to improve ShuntCheck's specificity in our bench model. In Phase 2, we will test the Micro- Pumper/ShuntCheck combination in a series of human studies, beginning with a 30 patient pilot study and concluding with a 300 patient clinical validation study comparing ShuntCheck patency results to clinical outcomes of symptomatic pediatric patients who present at the Emergency Departments of Children's Hospitals. By the end of Phase 2, we anticipate having accumulated sufficient data to enable submission of a pre-market notification (510(k)) to the FDA for the Micro-Pumper (in conjunction with ShuntCheck). The result of this work will be an important change in the diagnostic algorithm currently used to manage symptomatic hydrocephalus patients. Given the need for a non-invasive method to accurately diagnose shunt failure, the potential savings over alternative methods and the potential for improved patient outcomes, the data from this study will support a product which is commercially viable and extremely important.
PUBLIC HEALTH RELEVANCE: This proposal supports the development of a portable, non-invasive tool which will improve the diagnostic accuracy of CSF shunt patency testing such as radionuclide studies and ShuntCheck tests. This will improve clinical care for pediatric hydrocephalus patients with suspect shunt malfunction and could lead to an important change in the standard diagnostic pathway currently used to manage symptomatic hydrocephalus patients.