Optical Detection of the Pre-seizure State

癫痫发作前状态的光学检测

• 批准号: 8738724
• 负责人: DEVIN K BINDER
• 金额: $ 43.75万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8738724
• 关键词: Acute; Animal Model; Animals; Behavioral; Benchmarking; Biomedical Engineering; Brain; Brain Diseases; Characteristics; Chronic; Clinical; Data; Detection; Development; Electroencephalography; Epilepsy; Extracellular Space; Focal Seizure; Generalized seizures; Goals; Gold; Health; Hippocampus (Brain); Human; Image; Implant; In Vitro; Injection of therapeutic agent; Kainic Acid; Knowledge; Lead; Light; Measures; Methods; Microelectrodes; Mission; Modeling; Monitor; Mus; Neurosciences; Optical Coherence Tomography; Optical Methods; Optics; Patients; Public Health; Quality of life; Recurrence; Refractory; Research; Resolution; Seizures; Sensitivity and Specificity; Signal Transduction; Slice; Structure; System; Techniques; Technology; Testing; Time; Tissues; United States National Institutes of Health; Work; absorption; base; clinical application; clinically relevant; constriction; electric impedance; improved; in vitro Model; in vitro activity; in vivo; innovation; innovative technologies; minimally invasive; multidisciplinary; novel; relating to nervous system; research study; spatiotemporal; symposium

DESCRIPTION (provided by applicant): Reliable means of detecting changes which occur during the "pre-seizure state" could serve as a method of seizure prediction, a benchmark in epilepsy research (NIH Curing Epilepsy Conferences, 2000 and 2007). Our preliminary data indicate pre-seizure constriction in brain extracellular space (ECS) accompanied by reduction in near-infrared (NIR) optical scattering prior to detection of seizure by electroencephalography (EEG). The objective in this application is to determine the optical characteristics of the pre-seizure state in clinically relevant animal models of epilepsy. Three specific aims will be pursued: (1) To test the hypothesis that optical signals of the pre-seizure state can be used to predict epileptiform activity in vitro. Our preliminary data indicate that optical coherence tomography (OCT)-derived signals precede epileptiform activity in vitro. In this Aim, we will characterize the optical changes that occur prior to epileptiform activity in vitro in the hippocampal slice using simultaneous high-resolution microelectrode array (MEA) and OCT recordings. These experiments will fully define the optical changes occurring during the pre-seizure state and during epileptiform activity in vitro. (2) To test the hypothesis that optical signals of the pre-seizure state can be used to predict acute seizures in vivo. Our preliminary data indicate that OCT-derived reflectance intensity decreases prior to seizures in vivo (Eberle et al., 2012). In this Aim, we will test the ability of optical signal detection via OCT imaging to detect the pre-seizure state in vivo in well-established models of generalized and focal acute cortical seizures. These experiments will validate the existence of pre-seizure optical changes in distinct seizure models and provide proof-of-concept for the prediction of seizure onset in vivo with optical methods. (3) To test the hypothesis that implanted fiberoptic NIR probes can be used to detect the pre-seizure state of epileptic animals. Our preliminary data indicate that fiberoptics stereotactically implanted in mouse hippocampus demonstrate reduction in NIR reflectance prior to acute seizures in vivo. The gold standard for clinical application would be to reliably detect a spontaneous seizure in an epileptic animal. Therefore, in this Aim we will apply our novel fiberoptic NIRS detection system to a well-established animal model of chronic epilepsy (intrahippocampal kainic acid model). Sensitivity, specificity, and time course of optical NIR reflectance changes before and during chronic spontaneous seizures will be determined. These experiments will provide proof-of-principle for the efficacy of implanted fiberoptic monitoring to detect epileptic seizures for the first time. Our approach is innovative in (i) focusing on optical scattering changes rather than absorption changes as in prior studies; (ii) the first combination of MEA and OCT technologies in vitro and in vivo; (iii) use of novel fiberoptic NIR probes to measure optical changes in deep brain structures prior to seizures in vivo for the first time. The proposed research is significant because the results will elucidate optical characteristics of the pre-seizure state and lead to methods to detect focal and generalized seizures with unprecedented spatiotemporal resolution.

描述（由申请人提供）：检测“癫痫发作前状态”期间发生的变化的可靠方法可以作为癫痫发作预测的方法，癫痫研究的基准（NIH 治疗癫痫会议，2000 年和 2007 年）。我们的初步数据表明，在通过脑电图（EEG）检测癫痫发作之前，大脑细胞外空间（ECS）发生癫痫前收缩，并伴有近红外（NIR）光学散射的减少。本申请的目的是确定临床相关癫痫动物模型中癫痫发作前状态的光学特征。我们将追求三个具体目标：（1）检验癫痫发作前状态的光信号可用于体外预测癫痫样活动的假设。我们的初步数据表明，光学相干断层扫描（OCT）产生的信号先于体外癫痫样活动。在这个目标中，我们将使用同步高分辨率微电极阵列 (MEA) 和 OCT 记录来表征海马切片中癫痫样活动之前发生的光学变化。这些实验将充分定义在癫痫发作前状态和体外癫痫样活动期间发生的光学变化。 (2)检验癫痫发作前状态的光信号可用于预测体内急性癫痫发作的假设。我们的初步数据表明，OCT 衍生的反射强度在体内癫痫发作之前降低（Eberle 等，2012）。在此目标中，我们将测试通过 OCT 成像进行光信号检测的能力 在全面和局灶性急性皮质癫痫发作的完善模型中检测体内癫痫发作前状态。这些实验将验证不同癫痫模型中癫痫发作前光学变化的存在，并为利用光学方法预测体内癫痫发作提供概念验证。 (3) 检验植入式光纤近红外探头可用于检测癫痫动物癫痫前状态的假设。我们的初步数据表明，立体定向植入小鼠海马体中的光纤在体内急性癫痫发作之前表现出近红外反射率的降低。临床应用的黄金标准是 可靠地检测癫痫动物的自发性癫痫发作。因此，在这个目标中，我们将把我们的新型光纤 NIRS 检测系统应用于成熟的慢性癫痫动物模型（海马内红藻氨酸模型）。光学的灵敏度、特异性和时程 将确定慢性自发性癫痫发作之前和期间的近红外反射率变化。这些实验将首次为植入式光纤监测检测癫痫发作的有效性提供原理验证。我们的方法具有创新性：（i）关注光学散射变化，而不是像之前的研究那样关注吸收变化； (二) 首次将 MEA 和 OCT 技术在体外和体内结合； (iii) 首次使用新型光纤近红外探头测量体内癫痫发作前深部脑结构的光学变化。拟议的研究意义重大，因为结果将阐明癫痫发作前状态的光学特征，并产生以前所未有的时空分辨率检测局灶性和全身性癫痫发作的方法。