SBIR-STTR Award

Direct to Phase II

Hydrocephalus is a neurological disorder caused by buildup of excess cerebrospinal fluid (CSF) in the brain, and leads to lethargy, seizures, coma, or death. It is treated with the surgical implantation of a catheter, known as a ventricular shunt, that diverts excess CSF away from the brain and into a distal absorptive site, such as the abdomen. Unfortunately, due to occlusion or mispositioning, shunts have extremely high failure rates - 51% in 2 years, and 98% over 10 years - and often require corrective surgical procedures, known as revisions. 125,000 shunt implantations or revisions are performed annually in the United States, at a cost of $2 billion. Diagnosing shunt failure is extremely difficult, due the non-specific nature of its symptoms. Imaging tests such as CT are commonly used despite their long-term radiation exposure risks and invasive tests such as CSF aspiration and radionuclide tracing are painful and carry significant infection risks. All the above tests have poor diagnostic performance, with low sensitivities (~80%) and specificities (~55%), in large part because they do not directly measure flow dynamics, arguably the most important and relevant shunt performance metric. The continuous, non-invasive, real-time monitoring of CSF flow through implanted shunts represents a critical unmet need. Clinicians would use these data for point-of-care diagnostics, and researchers would use them to better understand shunt failure, and elucidate the pathophysiology of poorly-understood conditions such as normal-pressure hydrocephalus. The present proposal addresses this need by capitalizing on existing wireless sensor hardware to develop the first skin mounted wireless product to give quantitative CSF flow data in implanted shunts. Using precise measurements of thermal transport, we will develop novel algorithms to characterize and quantify flow through underlying shunts with high accuracy. Preliminary patient data, benchtop tests, and computer modeling confirm the ability of the sensor to produce high-quality flow data while being mechanically unobtrusive to the patient. Phase I activities will validate the sensor on large animal models, develop algorithms to deliver quantitative flow data, and implement a quality management system to govern software development, ultimately leading to IRB approval for clinical testing. Phase II activities will validate diagnostic value of the sensor's performance clinically through a human trial, ultimately leading to a marketing submission to the FDA.

Public Health Relevance Statement:
Narrative Hydrocephalus is a common and costly condition caused by the accumulation of cerebrospinal fluid (CSF) in the brain, occurring in 1-5 of every 1,000 live births, is usually treated with ventricular shunts which, unfortunately have extremely high failure rates due to a diverse set of factors including occlusion, mispositioning, or kinking. Consequently, physicians rely on a complicated, expensive, and often inconclusive suite of tests, including those that expose patients to significant radiation, to make clinical decisions. A precise, rapid, noninvasive way to quantitatively monitor shunt function represents a critical unmet need.

Project Terms:
Abdomen; Abdominal; Adult; 21+ years old; Adult Human; adulthood; Affect; Algorithms; Animals; Brain; Brain Nervous System; Encephalon; Cerebrospinal Fluid; cerebral spinal fluid; spinal fluid; Cerebrospinal fluid shunts procedure; CSF shunt; Cerebrospinal Fluid Shunts; Child; 0-11 years old; Child Youth; Children (0-21); youngster; Clinical Research; Clinical Study; Coma; Comatose; Cessation of life; Death; Diagnosis; Electronics; electronic device; Exhibits; Freezing; Goals; Gold; Head; Headache; Cephalalgia; Cephalgia; Cephalodynia; Cranial Pain; Head Pain; head ache; Human; Modern Man; Hydrocephalus; Hydrocephaly; hydrocephalic; Normal Pressure Hydrocephalus; Hakim Syndrome; NPH; Ice; Laboratories; Lethargies; Magnetic Resonance Imaging; MR Imaging; MR Tomography; MRI; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; NMR Imaging; NMR Tomography; Nuclear Magnetic Resonance Imaging; Zeugmatography; Marketing; nervous system disorder; Nervous System Diseases; Neurologic Disorders; Neurological Disorders; neurological disease; Obstruction; Pain; Painful; Patients; Peer Review; Physicians; Pilot Projects; pilot study; Program Development; Publishing; Radioisotopes; Radioactive Isotopes; Radionuclides; Research Personnel; Investigators; Researchers; Risk; Seizures; Computer software; Software; Specificity; Technology; Temperature; Testing; Time; X-Ray Computed Tomography; CAT scan; CT X Ray; CT Xray; CT imaging; CT scan; Computed Tomography; Tomodensitometry; X-Ray CAT Scan; X-Ray Computerized Tomography; Xray CAT scan; Xray Computed Tomography; Xray computerized tomography; catscan; computed axial tomography; computer tomography; computerized axial tomography; computerized tomography; Translating; United States; Universities; Washington; Work; Measures; Catheters; Device Designs; Device Safety; Journals; Magazine; base; sensor; Distal; Site; Clinical; repaired; repair; Phase; Failure; Childhood; pediatric; Measurement; Functional disorder; Dysfunction; Physiopathology; pathophysiology; academic review; fluid; liquid; Liquid substance; Contracting Opportunities; Contracts; Community Physician; tool; Diagnostic; Nature; programs; mechanical; Mechanics; Techniques; System; Live Birth; Neurological Surgery; Neurosurgical Procedures; Shunt; shunts; Shunt Device; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; interest; Medical center; Performance; cerebrospinal fluid flow; Animal Models and Related Studies; model of animal; model organism; Animal Model; novel; model-based simulation; models and simulation; ventricular system; Devices; Manpower; personnel; Human Resources; Abscission; Extirpation; Removal; Surgical Removal; resection; Excision; Radiation; Sampling; develop software; developing computer software; software development; Skin; Thickness; Thick; Address; Symptoms; Data; research clinical testing; Clinical Evaluation; Clinical Testing; clinical test; Validation; Wireless Technology; wireless; Monitor; Tracer; Ventricular; Development; developmental; Image; imaging; cost; design; designing; Implant; implantation; scientific computing; standard of care; product development; point-of-care diagnostics; clinical decision-making; Institutional Review Boards; IRB; IRBs; flexible electronics; flex circuit; Radiation exposure; clinical diagnostics; recruit; real time monitoring; realtime monitoring; infection risk; Computer Models; Computerized Models; computational modeling; computational models; computer based models; computerized modeling; algorithm development; cost estimate; cost estimation; porcine model; pig model; piglet model; swine model