Noninvasive Functional and Cellular Imaging of Epilepsy

癫痫的无创功能和细胞成像

• 批准号: 8020033
• 负责人: HUABEI JIANG
• 金额: $ 26.64万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-15 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8020033
• 关键词: Affect; American; Animal Model; Animals; Antiepileptic Agents; Blood Vessels; Blood Volume; Brain Neoplasms; Cellular Morphology; Cerebrovascular Circulation; Cerebrum; Clinical; Computer software; Coupling; Development; Disabled Persons; Disease; Electroencephalography; Epilepsy; Functional Imaging; Goals; Image; Image Enhancement; Imaging technology; Individual; Life; Linear Models; Measures; Metabolism; Modality; Modeling; Neurons; Non-linear Models; Operative Surgical Procedures; Optics; Oxygen; Oxyhemoglobin; Parkinson Disease; Pharmaceutical Preparations; Research; Resistance; Resolution; Scheme; Seizures; Syndrome; System; Techniques; Testing; Tissues; cellular imaging; cost; deoxyhemoglobin; design and construction; diffuse optical tomography; hemodynamics; improved; in vivo; neuroimaging; public health relevance; research study; response; simulation

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. PUBLIC HEALTH RELEVANCE: Many 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 by developing a new imaging technology, and thereby offer curative epilepsy surgery for this devastating disease. Both technological development and in vivo animal studies are proposed in this application.

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缺陷，比帕金森病或脑肿瘤致残的人数还要多。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。癫痫包括40多种临床综合征，影响全世界4000万人。大约25%接受抗癫痫药物治疗的个体癫痫发作控制不足；然而，如果能够精确定位癫痫发作的病灶，80%的耐药性癫痫患者可能会通过手术治愈。拟议的研究将大大提高我们定位这种病灶的能力，从而为这种毁灭性疾病提供治愈性癫痫手术。我们假设漫射光学断层扫描（DOT）提供了一种新的功能和细胞神经成像方式，用于无创跟踪癫痫发作期间的动态变化。DOT能够对组织功能进行成像，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（cro2）。此外，我们表明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前所未有的癫痫发作和发作间期活动的定位，这是任何现有神经成像技术都无法提供的功能。虽然本项目的主要目标是开发一种精确定位癫痫病灶的DOT系统，但我们也建议在癫痫动物模型中使用并发脑电图（EEG）和DOT无创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)开发一套改进小动物DOT成像的图像增强方案，并建立将电生理记录与DOT测量的血流动力学/细胞反应相结合的线性和非线性模型；(3)通过仿真和模拟实验，对多光谱DOT系统的软硬件集成功能进行评估和优化；(4)利用动物模型对DOT系统和神经-血管/神经细胞耦合模型进行测试和评估。