EpiZode: Noninvasive Seizure Screening in Preclinical Models of Epilepsy

EpiZode：癫痫临床前模型的无创性癫痫发作筛查 迫切需要研究癫痫和其他癫痫发作疾病的治疗方案。动物 模型越来越多地用于了解疾病机制和筛选有希望的治疗方法， 接近。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EEG测量是首选的验证方法。这严重限制了发展的速度和规模。 调查在获得性癫痫模型中，动物通常接受治疗以诱导癫痫持续状态- 一段持续的沉默期，然后是一段潜伏期，在这段时间里，大脑会重新连接， 自发性复发性癫痫是慢性癫痫的标志潜伏期的持续时间和 动物患癫痫的可能性都是不确定的。动物必须观察数周， 在他们准备好进行实验之前确认癫痫。在此潜伏期，癫痫发作通常是 通过视觉观察或视频审查来记录，这是乏味的并且容易出错。商业系统 因此，自动无创性癫痫发作检测对癫痫研究人员来说是非常宝贵的。 Signal Solutions，LLC开发了压电传感器技术，用于非侵入性、高通量 啮齿动物的行为监测世界各地的睡眠/昼夜节律研究人员都在使用这一方法， 以>90%的准确度区分睡眠和清醒。肯塔基州大学的Sunderam实验室 进一步证明了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，以：1。测试的可行性 使用非侵入性压电膜传感器检测啮齿动物中的癫痫发作; 2.压电检测， 癫痫啮齿类动物的同步EEG记录;以及3.测试使用较小剖面压电的可行性 传感器和红外成像仪，用于缉获筛查和核查。该研究成功证实了 这些目标的可行性。 在这个II期STTR提案中，我们将进一步开发准确的非侵入性癫痫筛查方法， 啮齿动物模型通过以下目的：1.开发用于检测显性和隐性的算法 使用小型压电传感器的癫痫发作; 2.发送一个原型系统进行beta测试， 动物模型和完善系统的基础上反馈; 3.开发和验证新型传感器配置 算法，用于准确的癫痫发作检测和归属组圈养的癫痫动物。 设想的产品是一个交钥匙系统，方便的非侵入性癫痫筛查小动物 定制或商业笼中的癫痫模型，最大限度地减少了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制药行业的实验室 从事抗癫痫药物的高容量筛选。

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.