EpiZode: Noninvasive Seizure Screening in Preclinical Models of Epilepsy

EpiZode：癫痫临床前模型中的无创癫痫筛查

基本信息

批准号：
10260562
负责人：
Sridhar Sunderam
金额：
$ 84.3万
依托单位：
SIGNAL SOLUTIONS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-15 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10260562
关键词：
Acute Address Aftercare Algorithms Animal Experimentation Animal Model Animals Antiepileptic Agents Behavior Behavior monitoring Behavioral Brain Chronic Circadian Rhythms Communities Computer software Convulsants Custom Detection Development Disease Drug Screening Electrodes Electroencephalography Epilepsy Epileptogenesis Essential Tremor Evaluation Family Feedback Film Floor Frontal Lobe Epilepsy Funding Genes Genetic Models Government Harmaline Industrialization Investigation Kentucky Knock-out Laboratory Animals Lafora Disease Measurement Measures Methods Modeling Monitor Mus Outcome Persons Pharmacologic Substance Phase Post-Traumatic Epilepsy Pre-Clinical Model Rattus Research Research Personnel Resources Rodent Rodent Model SCN8A gene Sampling Seizures Signal Transduction Sleep Sleep Stages Small Business Technology Transfer Research Status Epilepticus System Technology Temporal Lobe Epilepsy Testing Therapeutic Time Tonic - clonic seizures Tremor United States National Institutes of Health Universities Validation Video Recording Visual Wakefulness acquired epilepsy base circadian dravet syndrome drug development feasibility testing imager interest kainate natural hypothermia non rapid eye movement non-invasive monitor novel perinatal stroke pressure prototype relating to nervous system respiratory screening sensor sensor technology social source localization success trait treatment effect voltage

项目摘要

EpiZode: Noninvasive Seizure Screening in Preclinical Models of Epilepsy There is an urgent need for research into treatment options for epilepsy and other seizure disorders. Animal models are increasingly used to understand disease mechanisms and to screen promising therapeutic approaches. Animal epilepsy model use typically requires expensive and labor-intensive experimentation, with invasive EEG measurements being the preferred method of validation. This severely limits the pace and scale of investigation. In models of acquired epilepsy, animals usually undergo treatment to induce status epilepticus— a period of unremitting seizure—followed by a latent period during which the brain rewires itself to generate spontaneously recurring seizures, the hallmark of chronic epilepsy. The duration of the latent period and the likelihood that an animal will develop epilepsy are both uncertain. Animals must be observed for weeks to confirm epilepsy before they are ready for experimentation. During this latent period, seizures are commonly documented by visual observation or video review, which are tedious and prone to error. A commercial system for automated noninvasive seizure detection would therefore be invaluable to epilepsy researchers. Signal Solutions, LLC, has developed piezoelectric sensor technologies for noninvasive, high-throughput behavioral monitoring in rodents. This is being used by sleep/circadian researchers around the world, and discriminates sleep from wakefulness with >90% accuracy. The Sunderam Lab at the University of Kentucky has further demonstrated that these piezo sensors can distinguish REM and NREM stages of sleep in mice. To address the needs of epilepsy researchers, we performed a Phase I STTR study to: 1. Test the feasibility of epilepsy onset detection in rodents using noninvasive piezo film sensors; 2. Validate piezo detections against simultaneous EEG recordings in rodents with epilepsy; and 3. Test the feasibility of using smaller profile piezo sensors and an infrared imager for seizure screening and verification. The study successfully confirmed the feasibility of these aims. In this Phase II STTR proposal, we will further develop methods for accurate noninvasive seizure screening in rodent models through the following objectives: 1. Develop algorithms for detection of both overt and subtle seizures using small form factor piezo sensors; 2. Send a prototype system out for beta testing on different animal models and refine the system based on feedback; 3. Develop and validate novel sensor configurations algorithms for accurate seizure detection and attribution in group-housed epileptic animals. The envisioned product is a turnkey system for convenient noninvasive seizure screening in small animal models of epilepsy in custom or commercial cages that minimizes the need for invasive and resource-intensive EEG analysis. Potential customers include academic research labs as well as labs in the pharmaceutical sector engaged in high-volume screening of antiepileptic drugs.

Epizode：癫痫临床前模型中的无创癫痫发作筛查迫切需要研究癫痫和其他癫痫病的治疗选择。动物模型越来越多地用于理解疾病机制并筛查有希望的治疗方法。动物癫痫模型的使用通常需要昂贵且劳动密集型的实验，并需要侵入性脑电图测量是首选的验证方法。这严重限制了投资。在获得癫痫的模型中，动物通常接受治疗以诱导癫痫持续状态 - 一个不易癫痫发作的时期 - 由一个潜在时期遵循，在此期间，大脑会重新布线产生赞助癫痫发作，这是慢性癫痫的标志。潜在时期和动物发育癫痫的可能性都是不确定的。必须观察动物数周在准备实验之前确认发作。在这个潜在时期，癫痫发作通常是通过视觉观察或视频审查记录，这些审查乏味且容易出错。商业系统因此，对于自动化的非侵入性癫痫发作检测对于癫痫研究人员来说将是无价的。 Signal Solutions，LLC已开发了无创，高通量的压电传感器技术啮齿动物的行为监测。这是由世界各地的睡眠/昼夜研究人员使用的 > 90％的精度将睡眠与清醒区分开。肯塔基大学的Sunderam实验室进一步证明，这些压电传感器可以区分小鼠睡眠的REM和NREM阶段。为了满足癫痫研究人员的需求，我们进行了I期STTR研究：1。测试的可行性使用非侵入性压电膜传感器在啮齿动物中检测癫痫发作； 2。验证压电检测简单的脑电图记录癫痫病啮齿动物；和3。测试使用较小的轮廓压电的可行性传感器和红外成像仪用于癫痫发作和验证。该研究成功证实了这些目标的可行性。在此II阶段的STTR提案中，我们将进一步开发用于准确非侵入性癫痫发作筛查的方法通过以下对象的啮齿动物模型：1。开发算法，以检测明显和微妙的算法使用小型压电传感器的癫痫发作； 2。发送原型系统以进行不同的beta测试动物模型并根据反馈来完善系统； 3。开发和验证新型传感器配置在癫痫动物中精确癫痫发作检测和属性的算法。设想的产品是一个交钥匙系统，用于在小动物中方便的无创癫痫发作筛查定制或商业笼子中癫痫的模型，可以最大程度地减少对侵入性和资源密集型的需求脑电图分析。潜在客户包括学术研究实验室以及药品领域的实验室从事抗癫痫药的大规模筛查。