EpiZode: Noninvasive Seizure Screening in Preclinical Models of Epilepsy

EpiZode：癫痫临床前模型中的无创性癫痫筛查 迫切需要研究癫痫和其他癫痫发作障碍的治疗方案。动物 模型越来越多地被用于了解疾病机制和筛选有前景的治疗方法 接近了。动物癫痫模型的使用通常需要昂贵和劳动密集型的实验， 有创性脑电测量是验证的首选方法。这严重限制了 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- 无休止的癫痫发作--之后是一段潜伏期，在此期间大脑重新连接自身以产生 自发性癫痫发作，是慢性癫痫的标志。潜伏期的持续时间和 动物罹患癫痫的可能性都是不确定的。动物必须观察数周才能 在他们准备好进行实验之前，先确认癫痫。在这一潜伏期内，癫痫发作通常 通过目视观察或视频审查来记录，这些方法繁琐且容易出错。一个商业体系 因此，自动化的非侵入性癫痫检测对癫痫研究人员来说是非常有价值的。 Signal Solutions，LLC已开发出用于非侵入性、高通量的压电传感器技术 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技术，而且 以90%的准确率区分睡眠和清醒状态。肯塔基大学的桑达姆实验室 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，我们进行了一项第一阶段的STTR研究：1.测试 使用非侵入性压电膜传感器检测啮齿动物癫痫发作；2.验证压电检测对 同时记录患有癫痫的啮齿动物的脑电；以及3.测试使用较小剖面压电体的可行性 传感器和红外成像仪，用于癫痫筛查和核实。这项研究成功证实了 这些目标的可行性。 在第二阶段的建议中，我们将进一步发展准确的非侵入性癫痫筛查方法。 通过以下目标建立啮齿动物模型：1.开发检测显性和隐蔽性的算法 建立动物模型，并根据反馈改进系统；3.开发和验证新型传感器配置 群养癫痫动物癫痫发作的准确检测和归因的算法。 设想的产品是一种交钥匙系统，用于对小动物进行方便的非侵入性癫痫筛查 定制或商用笼子中的癫痫模型，最大限度地减少了对侵入性和资源密集型的需求 脑电分析。潜在客户包括学术研究实验室和制药部门的实验室。 从事抗癫痫药物的大批量筛选。

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.