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Noninvasive Functional and Cellular Imaging of Epilepsy

癫痫的无创功能和细胞成像

基本信息

批准号：
8415577
负责人：
HUABEI JIANG
金额：
$ 29.26万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-15 至 2015-01-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：今天大约有250万美国人患有癫痫和癫痫相关的缺陷，超过帕金森病或脑瘤的残疾。癫痫在美国的影响是巨大的，全国癫痫发作和癫痫的总成本约为125亿美元。癫痫由40多种临床综合征组成，影响着全球4000万人。大约25%接受抗癫痫药物治疗的人癫痫发作控制不佳;然而，如果能够精确定位癫痫发作病灶，80%的耐药癫痫患者可能会通过手术治愈。这项研究将大大提高我们定位这些病灶的能力，从而为这种毁灭性疾病提供治疗性癫痫手术。我们假设，扩散光学断层扫描（DOT）提供了一个新的功能和细胞神经成像模式，非侵入性跟踪动态变化，在癫痫发作的发生。 DOT具有成像组织功能的能力，包括氧合血红蛋白（HbO 2）、脱氧血红蛋白（Hb）、脑血容量（CBV）、脑血流量（CBF）和脑氧代谢率（CMRO 2）。此外，我们表明，DOT也可以提供脑细胞形态，是来自组织散射光谱。鉴于光学模态的高时间和空间分辨率，所提出的血流动力学和细胞成像将提供前所未有的发作和发作间期癫痫发作活动的定位，这是现有神经成像技术无法提供的功能。虽然这个项目的主要目标是开发一个DOT系统，准确定位癫痫病灶，我们还建议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使用并发脑电图（EEG）和DOT非侵入性癫痫发作的动物模型。这种耦合研究对于解释功能/细胞成像结果变得越来越重要，并且可能有助于预测癫痫发作。为了验证这一假设，我们提出了以下具体目标：（1）设计、构建和测试一个用于功能/细胞DOT成像的快速多光谱光学系统：（2）开发一套用于改进小动物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/细胞反应耦合的线性和非线性模型;（3）通过仿真和体模实验，对多光谱DOT系统的硬件和软件组件的集成功能进行评估和优化;（4）通过动物模型对所提出的DOT系统和神经-血管/神经-细胞耦合模型进行测试和评估。