Nanoelectronic enabled chronic quantification of neurovascular coupling

项目概要： 神经血管耦合，神经活动与血流动力学之间的密切时空关系 调节代谢底物的传递以满足神经元激活的需求，对于神经元的功能至关重要。 大脑结构和功能的完整性它也是现代神经成像技术的基础， 功能性磁共振成像利用血液动力学反应来描绘大脑功能。尽管其重要的基本和 临床重要性，血流动力学变化与神经活动之间的定量关系 包括耦合的空间范围仍然是基本的;脑血管的定量影响 疾病对神经血管偶联的影响及其对疾病严重程度和进展的依赖性， 替补演员这种知识差距限制了广泛应用的药物的精确临床解释。 神经影像学技术，以及明确针对神经血管损伤的治疗机会 耦合治疗。该项目的目标是提供时空分辨的量化 神经血管耦合在健康和中风和高血压的进展。前提是 神经血管耦合可以通过应用一种新的慢性多模式神经平台来量化和跟踪 同时映射神经活动和血液动力学参数， 解决了几个星期到几个月的动物行为。这是因为我们最近开发了一部小说 一种提供空间分辨神经活动记录的超柔性纳米电子神经电极 无缝组织整合和慢性光学访问。我们将联合收割机这些电极与一种新颖的 功能性光学成像系统，其同时成像和量化全视野脑血流 氧分压（pO 2）。我们将在行为小鼠中应用这种多模式系统来量化神经血管 耦合包括时空模式、功能形式和因发展而产生的变化 局部缺血、高血压以及两者。申请人认为，该申请极具创新性，因为它 整合了多个前沿的技术进步，提供了一个高度新颖和强大的组合， 技术，允许量化神经血管耦合在以前无法达到的时间和空间 政权。该应用程序是重要的，因为它预计将具有广泛的翻译重要性，无论是在 神经影像技术的精确临床解释，以及脑血管介入治疗 已知神经血管耦合严重受损的疾病。长期目标是 本研究旨在了解脑卒中和高血压患者神经血管耦联受损的机制 与人类患者发生的类似，以解开高血压的机制为主导， 脑卒中的危险因素，并改善高血压脑卒中患者的预防和干预策略。

PROJECT SUMMARY: Neurovascular coupling, the close spatial and temporal relationship between neural activity and hemodynamics that regulates delivery of metabolic substrates to meet the demands of neuronal activation, is crucial to the structural and functional integrity of the brain. It also forms the basis of modern neuroimaging techniques such as fMRI that use hemodynamic responses to map brain function. Despite of its significant fundamental and clinical importance, the quantitative relationship between changes in hemodynamics and neural activity including the spatial extent of the coupling remains rudimentary; the quantitative effects of cerebrovascular diseases on neurovascular coupling and their dependence on the severity and progression of the diseases are understudied. Such knowledge gaps impose limitations on the precise clinical interpretation of widely applied neuroimaging techniques, and the therapeutic opportunities to clearly target the impairment of neurovascular coupling for treatment. The objective of this project is to provide spatiotemporally resolved quantification of neurovascular coupling in health and during the progression of stroke and hypertension. The hypothesis is that neurovascular coupling can be quantified and tracked by applying a novel chronic multimodal neural platform that simultaneously map both neural activity and hemodynamic parameters with high spatial- and temporal resolution over weeks to months in behaving animals. This is enabled by our recent development of a novel type of ultraflexible nanoelectronic neural electrodes that provide spatially resolved neural activity recording with seamless tissue integration and chronic optical access. We will combine these electrodes with a novel functional optical imaging system that simultaneously images and quantifies the full-field cerebral blood flow and oxygen tension (pO2). We will apply this multimodal system in behaving mice to quantify neurovascular coupling including the spatiotemporal pattern, the functional form, and the alteration due to progressing ischemia, hypertension and both. The application is highly innovative, in the applicant’s opinion, because it integrates technical advancements at multiple fronts to provide a highly novel and powerful combination of techniques that permits quantification of neurovascular coupling in previously unattainable temporal and spatial regimes. The application is significant, because it is expected to have broad translational importance both in the precise clinical interpretation of neuroimaging techniques, and in the intervention of cerebrovascular diseases where neurovascular coupling is known to be severely compromised. The long-term goal of this project is to understand the impairment of neurovascular coupling in stroke and hypertension with mechanisms similar to those occurred in human patient in order to unravel the mechanism of hypertension as the leading risk factor for stroke, and to improve prevention and intervention strategies for hypertensive stroke patients.