Noninvasive Functional and Cellular Imaging of Epilepsy

描述(申请人提供)：目前约有250万美国人患有癫痫和癫痫相关缺陷，超过帕金森病或脑瘤致残的人数。癫痫在美国的影响是巨大的，全国在癫痫发作和癫痫方面的总成本约为125亿美元。癫痫由40多种临床症状组成，影响全球4000万人。大约25%接受抗癫痫药物治疗的患者癫痫发作控制不充分；然而，如果能够准确定位癫痫发作灶，80%的药物抵抗型癫痫患者可能会通过手术治愈。这项拟议的研究将极大地提高我们定位这些病灶的能力，从而为这种毁灭性的疾病提供根治性的癫痫手术。我们假设扩散光学断层扫描(DOT)为非侵入性追踪癫痫发作过程中的动态变化提供了一种新的功能和细胞神经成像手段。DOT具有成像组织功能的能力，包括氧合血红蛋白(HBO2)、脱氧血红蛋白(Hb)、脑血容量(CBV)、脑血流量(CBF)和脑氧代谢率(CMRO2)。此外，我们还表明，DOT还可以提供来自组织散射光谱的脑细胞形态。鉴于光学模式的高时间和空间分辨率，拟议的血流动力学和细胞成像将提供对发作期和发作间期发作活动的前所未有的定位，这是任何现有的神经成像技术都无法提供的特征。虽然本项目的主要目标是开发一种用于准确定位癫痫灶的DOT系统，但我们也建议在癫痫动物模型中使用并行脑电(EEG)和DOT无创性地研究神经元活动和血流动力学/细胞反应之间的神经-血管和神经细胞耦合。这种耦合研究对解释功能/细胞成像结果正变得越来越重要，并可能有助于预测癫痫发作。为了验证这一假设，我们建议完成以下具体目标：(1)设计、构建和测试用于功能/细胞DOT成像的快速多光谱光学系统；(2)开发一套用于改善小动物DOT成像的图像增强方案，并开发将电生理记录与DOT测量的血流动力学/细胞响应相耦合的线性和非线性模型；(3)通过模拟和体模实验，评估和优化多光谱DOT系统硬件和软件组件的集成功能；(4)利用动物模型对所提出的DOT系统和神经-血管/神经细胞耦合模型进行验证和评价。

DESCRIPTION (provided by applicant): Approximately 2.5 million Americans live with epilepsy and epilepsy-related deficits today, more than disabled by Parkinson disease or brain tumors. The impact of epilepsy in the US is significant with a total cost to the nation for seizures and epilepsy of approximately $12.5 billion. Epilepsy consists of more than 40 clinical syndromes affecting 40 million people worldwide. Approximately 25 percent of individuals receiving antiepileptic medication have inadequate seizure control; however, 80% individuals with medication resistant epilepsy might be cured through surgery if one were able to precisely localize the seizure focus. The proposed research will significantly advance our ability to localize such foci, and thereby offer curative epilepsy surgery for this devastating disease. We hypothesize that diffuse optical tomography (DOT) provides a new functional and cellular neuroimaging modality for non-invasively tracking dynamical changes during seizure occurrence. DOT has the ability to image tissue functions including oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), cerebral blood volume (CBV), cerebral blood flow (CBF) and rate of cerebral oxygen metabolism (CMRO2). In addition, we show that DOT can also provide cerebral cellular morphology that is derived from tissue scattering spectra. Given the high temporal and spatial resolution for optical modalities, the proposed hemodynamic and cellular imaging will offer unprecedented localization of both ictal and interictal seizure activities, a feature that is unavailable from any of the existing neuroimaging techniques. While the primary goal of this project is to develop a DOT system for accurate localization of epileptic focus, we also propose to study the neuro-vascular and neuro-cellular coupling between neuronal activity and hemodynamic/cellular response using concurrent electroencephalography (EEG) and DOT noninvasively in animal models of seizure. Such coupling study is becoming increasingly important for interpreting functional/cellular imaging results, and may be useful in predicting seizure onset. To test the hypothesis, we propose to complete the following specific aims: (1) To design, construct and test a fast multispectral optical system for functional/cellular DOT imaging; (2) To develop a set of image enhancement schemes for improved DOT imaging of small animals, and To develop both linear and nonlinear models that couple the electrophysiological recordings with the hemodynamic/cellular response measured by DOT; (3) To evaluate and optimize the integrated functioning of the hardware and software components of the multispectral DOT system, using simulation and phantom experiments; (4) To test and evaluate the proposed DOT system and neuro-vascular/neuro-cellular coupling models using animal models.