Optical Imaging of Seizure Activity in Adult Neocortex

描述(由申请人提供)： 脑组织光学特性的变化与神经元活动水平的变化有关。绘制这些由活动引起的光学变化的方法被称为内部光学信号成像(IIOS)，可以提供脑组织功能和病理活动的高分辨率地图。本征光学信号(LOS)被认为是由至少三种不同的生理机制的组合产生的：i)血容量的变化，ii)血液氧合的变化，iii)与神经元活动相关的离子通量引起的血液非依赖性光散射变化。这些成分中的每一个都提供了重要且独特的生理信息类型。与其他成像方法相比，iIOS具有几个优势，包括相对较低的成本，以及以高时间和空间分辨率绘制发作间期和发作期癫痫样活动的独特能力。因此，iIOS有可能成为癫痫研究和治疗的有力工具，具有广泛的适用性。然而，由于至少两个原因，iIOS在临床和实验室中的应用仍然有限。首先，对在脑组织中产生功能性和癫痫诱发的光学变化的生理机制的不完全了解限制了我们解释iIOS数据的能力。其次，在确定iIOS数据在空间和时间上与灵长类动物和人类的功能和癫痫样神经元活动的相关性方面，相对较少的严格努力。这个项目的主要目标是确定产生正常和癫痫诱发的LOS的生理机制，并建立LOS和癫痫样神经元活动之间的空间和时间关联。一旦这些目标实现，将采取第一步开发iIOS作为一种实用的方法，用于术中定位成年人类患者的新皮质癫痫灶。该项目的具体目标是：i)开发基于光学成像的光谱技术，使iIOS能够提供灵长类动物和人类患者的血液氧合、血容量和血液非依赖性变化的高分辨率地图；ii)结合iIOS和电生理学研究，更全面地了解癫痫发作活动与癫痫样皮质血流动力学和代谢变化之间的联系；iii)应用iIOS对术中癫痫发作活动的高分辨率定位。

DESCRIPTION (provided by applicant): Changes in the optical properties of brain tissue are associated with changes in the level of neuronal activity. The method of mapping these activity-evoked optical changes is known as 'imaging of intrinsic optical signals' (IIOS), and can provide high-resolution maps of functional and pathological activity in brain tissue. Intrinsic optical signals (lOS) are thought to be generated by a combination of at least three distinct physiological mechanisms: i) changes in blood volume, ii) changes in blood oxygenation, and iii) blood-independent light scattering changes resulting from ion fluxes associated with neuronal activity. Each of these components provides important and distinct types of physiological information. IIOS has several advantages over other imaging modalities that include its relative low cost, and its unique ability to map interictal and ictal epileptiform activity with high temporal and spatial resolution. Consequently, IIOS has the potential to become a powerful tool with broad applicability in the study and treatment of epilepsy. However, IIOS has remained of limited clinical and laboratory use for at least two reasons. First, incomplete knowledge about the physiological mechanisms that generate functionally- and seizure-evoked optical changes in brain tissue limits our ability to interpret IIOS data. Second, there has been relatively little rigorous effort in determining how well IIOS data correlates spatially and temporally to functional and epileptiform neuronal activity in primates and humans. The major goals of this project are to determine the physiological mechanisms that generate normal and seizure-evoked lOS, and to establish the spatial and temporal correlates between lOS and epileptiform neuronal activity. Once these goals are achieved, the first steps will be taken to develop IIOS as a practical method for the intraoperative localization of neocortical seizure foci in adult human patients. The specific aims of this project are to: i) develop optical imaging-based spectroscopic techniques that will enable IIOS to provide high-resolution maps of changes in blood oxygenation, blood volume, and blood-independent changes in primates and human patients; ii) combine IIOS and electrophysiological studies towards gaining a more complete understanding of the links between seizure activity and the epileptiform-evoked changes in cortical hemodynamics and metabolism; and iii) apply IIOS towards the high-resolution intraoperative localization of seizure activity in human patients.