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: 8101880
• 负责人: DARYL William HOCHMAN
• 金额: $ 33.49万
• 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/8101880
• 关键词: Accounting; Action Potentials; Address; Area; Atrophic; Blood; Blood Volume; Blood flow; Brain; Brain region; Cerebrovascular Circulation; Cerebrum; Clinical; Core-Binding Factor; Coupling; Data; Epilepsy; Erythrocytes; Goals; Health; 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; 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（CBF），体积（CBV）和氧合（CBO）如何因新皮层中的正常和癫痫神经元活性而异？该提案的重点是使用光学成像技术与电生理学和药理学研究结合使用的人类灵长类动物进行研究。内在光学信号（OI）的光学成像是这些研究中的一种重点技术，取决于氧和脱氧 - 血红蛋白对光的差异吸收。由于血容量或血液氧化，OI可以选择性地测量皮质组织的变化。新皮质血流动力学的进一步研究至少出于三个原因很重要。首先，更好地阐明脑血液动力学和神经元活性之间的定量关系代表了对体内脑生理学的更完整理解所需的基本知识。其次，确定正常和癫痫活性之间脑血动力学偶联的差异可能会阐明与血液动力学相关现象（例如血液体积的异常变化或新皮层组织的异常变化）通过癫痫发作引起的新皮层组织会导致组织的脑含量和其他病理学上的病理学上的epillectics of epiLeptics“”。第三，量化神经元活动与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在神经外科患者中定位功能和癫痫新皮层的实用临床工具的必要步骤。迄今为止，由于至少有两个原因，OI在癫痫研究中的使用有限：i）解释在各种光波长下获得的光学信号的问题尚未得到充分解决，ii）ii）ii）通常使用的是用于分析光学成像数据的临时方法，几乎​​没有用于开发严格的统计方法来制定量化的量化技术。该项目的主要目标是解决这些问题。提案中将解决三个具体目标：目标1：量化神经元活动的变化，CBF，CBV，CBO和光学成像之间的关系；目标2：开发用于建模和分析OI数据的实用统计方法，并旨在阐明在ICTAL和ICTICTAIS活动期间新皮层中血液机器人的变化与光学信号之间的关系。公共卫生相关性：非技术解释：当大脑的区域变得活跃时，血液的氧合和血流增加了这些活跃地区。这些活性依赖性的血液变化来自正常活性以及病理癫痫活性。该提案将解决两个主要目标，这些目标可能对癫痫的治疗具有临床意义。首先，它将研究癫痫活性如何改变灵长类动物和患有癫痫患者的人类大脑的血流和氧合的变化。该信息可能有助于更好地理解癫痫的基本机制。其次，将进一步开发一种实验光学成像技术，该技术能够以非常高的空间分辨率绘制活性引起的血液氧合和血流的变化。这种光学成像技术有可能为神经外科医生提供一种新的，更好的方法，用于在手术治疗期间识别癫痫发作的脑区域，以进行医学上棘手的癫痫。