Neocortical hemodynamics during epileptic activity in primates and humans

灵长类动物和人类癫痫活动期间的新皮质血流动力学

• 批准号: 7738550
• 负责人: DARYL William HOCHMAN
• 金额: $ 35.54万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738550
• 关键词: Accounting; Action Potentials; Address; Area; Atrophic; Blood; Blood Volume; Blood flow; Brain; Brain region; Cerebrovascular Circulation; Cerebrum; Clinical; Coupling; Data; Epilepsy; Erythrocytes; Goals; Heart; Hemoglobin; Human; Image; Imaging Techniques; Intractable Epilepsy; Knowledge; Label; Lasers; Light; Linear Models; Maps; Measurement; Measures; Methods; Microscopy; Modeling; Morphologic artifacts; Motion; Neocortex; Neurons; Neurosurgeon; Operative Surgical Procedures; Optics; Oxygen; Patients; Physiology; Primates; Qualitative Methods; Research; Resolution; Seizures; Signal Transduction; Statistical Methods; Surface; Techniques; Tissues; Work; absorption; arteriole; brain tissue; hemodynamics; imaging probe; in vivo; neocortical; optical imaging; public health relevance; research study; response; spatial relationship; tool

DESCRIPTION (provided by applicant): Statement of work: How do cerebral blood flow (CBF), volume (CBV), and oxygenation (CBO) vary in response to normal and epileptic neuronal activity in the neocortex? The focus of this proposal is to investigate this question in primates in humans using optical imaging techniques combined with electrophysiological and pharmacological studies. Optical imaging of intrinsic optical signals (OI), a technique of focus in these studies, depends on the differential absorption of light by oxy- and deoxy-hemoglobin. OI can selectively measure changes in cortical tissue due to either blood volume or blood oxygenation. Further study of neocortical hemodynamics is important for at least three reasons. First, a better elucidation of the quantitative relationships between cerebral hemodynamics and neuronal activity represents basic knowledge required for a more complete understanding of in vivo brain physiology. Second, identifying the differences in the coupling of cerebral hemodynamics between normal and epileptic activity may shed light on how hemodynamic-related phenomena, such as abnormal changes in blood volume or deoxygenation of neocortical tissue elicited by seizure activity may contribute to tissue atrophy and other pathological aspects of the "epileptic brain". Third, quantifying the temporal and spatial relationships between neuronal activity and neocortical hemodynamics is a necessary step towards developing optical imaging as a practical clinical tool for localizing functional and epileptic neocortex in neurosurgical patients. To date, OI has been of limited use in epilepsy research for at least two reasons: i) The problem of interpreting optical signals acquired at the various optical wavelengths has not been fully resolved, and ii) ad hoc or qualitative methods have typically been used for the analysis of optical imaging data, with very little work devoted towards developing rigorous statistical methods necessary for making OI a quantitative technique. A major goal of this project is to resolve these issues. Three specific aims will be addressed in the proposal: Aim 1: To quantify relationships between changes in neuronal activity, CBF, CBV, CBO, and optical imaging; Aim 2: To develop practical statistical methods for modeling and analysis of OI data, and Aim 3: To elucidate the relationships between hemodymanic changes and optical signals in neocortex during ictal and interical activity . PUBLIC HEALTH RELEVANCE: Non-technical explanation: When areas of the brain become active, there are increases in the oxygenation and flow of blood to those active regions. These activity-dependent changes in blood result from both normal activity, as well as from pathological epileptic activity. This proposal will address two major goals which could have clinical implications in the treatment of epilepsy. First, it will study how epileptic activity alters blood flow and oxygenation changes in the brain in primates and in humans suffering from epilepsy. This information may be helpful in better understanding the basic mechanisms of epilepsy. Second, an experiment optical imaging technique will be further developed that is capable of mapping activity-evoked changes in blood oxygenation and blood flow with very high spatial resolution. This optical imaging technique has the potential to provide the neurosurgeon with a new and better method for identifying epileptic brain regions during the surgical treatment for medically intractable epilepsy.

描述（由申请人提供）： 工作说明：脑血流量 (CBF)、容量 (CBV) 和氧合 (CBO) 如何响应新皮质中的正常和癫痫神经元活动而变化？该提案的重点是利用光学成像技术结合电生理学和药理学研究，在人类灵长类动物中研究这个问题。内在光信号（OI）的光学成像是这些研究的重点技术，它取决于氧合血红蛋白和脱氧血红蛋白对光的吸收差异。 OI 可以选择性地测量由于血容量或血氧引起的皮质组织的变化。出于至少三个原因，进一步研究新皮质血流动力学很重要。首先，更好地阐明脑血流动力学和神经元活动之间的定量关系代表了更全面地理解体内脑生理学所需的基础知识。其次，识别正常和癫痫活动之间脑血流动力学耦合的差异可能有助于揭示血流动力学相关现象（例如癫痫活动引起的血容量异常变化或新皮质组织脱氧）如何导致组织萎缩和“癫痫脑”的其他病理方面。第三，量化神经元活动和新皮质血流动力学之间的时间和空间关系是开发光学成像作为定位神经外科患者功能性和癫痫性新皮质的实用临床工具的必要步骤。迄今为止，OI 在癫痫研究中的应用有限，至少有两个原因：i）解释在各种光波长下获取的光信号的问题尚未完全解决，ii）通常使用临时或定性方法来分析光学成像数据，很少有工作致力于开发使 OI 成为定量技术所需的严格统计方法。该项目的一个主要目标是解决这些问题。该提案将解决三个具体目标： 目标 1：量化神经元活动、CBF、CBV、CBO 和光学成像变化之间的关系；目标 2：开发用于 OI 数据建模和分析的实用统计方法，目标 3：阐明发作期和间期活动期间新皮质的血流变化与光信号之间的关系。公共卫生相关性：非技术解释：当大脑区域变得活跃时，流向这些活跃区域的氧合和血流量就会增加。血液中这些活动依赖性变化是由正常活动以及病理性癫痫活动引起的。该提案将解决两个可能对癫痫治疗具有临床意义的主要目标。首先，它将研究癫痫活动如何改变灵长类动物和癫痫患者大脑中的血流和氧合变化。这些信息可能有助于更好地了解癫痫的基本机制。其次，将进一步开发一种实验光学成像技术，能够以非常高的空间分辨率绘制活动引起的血氧和血流变化。这种光学成像技术有可能为神经外科医生在难治性癫痫的手术治疗过程中提供一种新的、更好的方法来识别癫痫大脑区域。