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筛查迫切需要研究癫痫和其他动物癫痫病的治疗方案。模型越来越多地用于了解疾病机制和筛选有前途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。侵入性脑电图测量是首选的验证方法，这严重限制了验证的速度和规模。在获得性癫痫模型中，动物通常接受治疗以诱发癫痫持续状态—— 一段持续的癫痫发作期——随后是一段潜伏期，在此期间大脑重新布线以产生自发性反复发作，是慢性癫痫的标志，潜伏期的持续时间和发作期。动物患癫痫的可能性尚不确定，必须对动物进行数周的观察。在准备实验之前确认癫痫。在这个潜伏期，癫痫发作很常见。通过目视观察或视频审查进行记录，这是乏味且容易出错的商业系统。因此，自动无创癫痫发作检测对于癫痫研究人员来说是非常宝贵的。 Signal Solutions, LLC 开发了用于非侵入性、高通量的压电传感器技术世界各地的睡眠/昼夜节律研究人员正在使用啮齿动物的行为监测，以及肯塔基大学桑德拉姆实验室区分睡眠和清醒的准确率超过 90%。进一步证明这些压电传感器可以区分小鼠的 REM 和 NREM 睡眠阶段。为了满足癫痫研究人员的需求，我们进行了 I 期 STTR 研究，以： 1. 测试可行性使用无创压电薄膜传感器检测啮齿类动物的癫痫发作；2. 验证压电检测；患有癫痫的啮齿类动物的同步脑电图记录；以及 3. 测试使用更小外形压电的可行性用于癫痫筛查和验证的传感器和红外成像仪该研究成功证实了这一点。这些目标的可行性。在此 II 期 STTR 提案中，我们将进一步开发准确的无创癫痫筛查方法啮齿动物模型通过以下目标： 1. 开发用于检测明显和微妙的行为的算法使用小型压电传感器进行癫痫发作； 2. 发送原型系统在不同的设备上进行 beta 测试；动物模型并根据反馈完善系统；3.开发和验证新型传感器配置对群养的癫痫动物进行准确的癫痫发作检测和归因的算法。设想的产品是一个交钥匙系统，用于方便地对小动物进行无创癫痫筛查在定制或商业笼子中建立癫痫模型，最大限度地减少侵入性和资源密集型的需求脑电图分析的潜在客户包括学术研究实验室以及制药行业的实验室。从事抗癫痫药物的大批量筛选。