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相关。绘制这些活动诱发的光学变化的方法被称为“内在光学信号成像”（IIOS），并且可以提供脑组织中功能和病理活动的高分辨率地图。固有光信号（IOS）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）血氧的变化，以及iii）由与神经元活动相关的离子通量引起的与血液无关的光散射变化。这些组件中的每一个都提供重要且不同类型的生理信息。与其他成像方式相比，IIOS具有多项优势，包括其相对较低的成本，以及其以高时间和空间分辨率绘制发作间隙和发作癫痫样活动的独特能力。因此，IIOS有可能成为一个强大的工具，广泛适用于癫痫的研究和治疗。然而，至少有两个原因，IIOS在临床和实验室的使用仍然有限。首先，对脑组织中产生功能性和神经性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，相对较少进行严格的努力。本项目的主要目标是确定产生正常和癫痫诱发的IOS的生理机制，并建立IOS和癫痫样神经元活动之间的时空相关性。一旦这些目标实现，第一步将采取发展IIOS作为一个实用的方法，在成人患者的新皮层癫痫灶术中定位。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氧变化、血容量变化和非血液依赖性变化的高分辨率地图; ii）将联合收割机和电生理学研究结合起来，以便更全面地了解癫痫发作活动和癫痫样发作之间的联系-诱发皮质血流动力学和代谢的变化;和iii）将IIOS应用于人类患者中癫痫发作活动的高分辨率术中定位。

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.