SIGNAL SOLUTIONS, LLC STTR Phase I Award, April 2018

Noninvasive Seizure Screening in Preclinical Models of Epilepsy There is an urgent need for research into treatment options for epilepsy and other seizure disordersAnimal models are increasingly used to understand disease mechanisms and to screen promising therapeutic approachesAnimal epilepsy model use typically requires expensive and labor intensive experimentationwith invasive EEG measurements being the preferred method of validationThis severely limits the pace and scale of investigationIn models of acquired epilepsyanimals usually undergo treatment to induce status epilepticusa period of unremitting seizure followed by a latent period during which the brain rewires itself to generate spontaneously recurring seizuresevidence of chronic epilepsyThe duration of the latent period and the likelihood that an animal will develop epilepsy are both uncertainAnimals must be observed for weeks to confirm epilepsy before they are ready for experimentationDuring this latent periodseizures are commonly documented by visual observation or video reviewwhich are tedious and prone to errorA commercial system for automated noninvasive seizure detection would therefore be attractive to epilepsy researchersSignal SolutionsLLChas developed technology based on piezoelectric sensors for noninvasivehighthroughput behavioral monitoring of rodents that is currently used by research groups around the world to identify genes related to sleep and circadian rhythmsThe system discriminates sleep from wakefulness with overaccuracyThe Sunderam Lab at the University of Kentucky has further demonstrated using EEG analysis that these piezo sensors can be used to label REM and NREM stages of sleep in miceIn this STTR proposalPI Sunderam and co investigator Bauer will work with Signal Solutions to develop methods based on the piezo technology for accurate noninvasive seizure screening in rodent models of epilepsyThe result will be a validated system that minimizes the need for invasive and resource intensive EEG analysis or tedious video monitoringThe objectives of the project are the followingTest the feasibility of coarse detection of epilepsy onset in rodents using a noninvasive piezo sensorTrain a piezo classifier to accurately detect and quantify seizures in rodents with confirmed epilepsyandTest the utility of a miniature piezo sensor for seizure screening and an infrared imager for seizure verification and severity assessmentThe envisioned product is a turnkey system for convenient and noninvasive seizure screening in small animal models of epilepsy in custom or commercial cagesPotential customers include academic research labs as well as labs in the pharmaceutical sector engaged in high volume screening of antiepileptic drugs The development of treatments for epilepsy depends heavily on laboratory animal studies in which the effect of treatment on seizures is measuredSeizures are rare and unpredictableand monitoring animals for seizures requires tedious observation or review of video recordingsthe alternative is to record brain signalswhich requires invasive surgery to implant electrodesA new technology is proposed here that would enable completely noninvasive detection of seizures in animalsThe accuracy of this method will be compared with EEG analysis in an animal model of epilepsy