Nanoelectronic enabled chronic quantification of neurovascular coupling

纳米电子技术实现了神经血管耦合的长期定量

基本信息

批准号：
10115788
负责人：
Lan Luan
金额：
$ 17.8万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-12-18 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10115788
关键词：
Acute Affect Anesthesia procedures Angiotensin II Animals Blood - brain barrier anatomy Blood Pressure Brain Cerebrovascular Circulation Cerebrovascular Disorders Chronic Cicatrix Clinical Coupling Dependence Development Disease Progression Disease model Dose Electrodes Functional Magnetic Resonance Imaging Goals Health Human Hypertension Image Impairment Infarction Intervention Ischemia Knowledge Location Maps Measurement Measures Metabolic Modeling Modernization Mus Nature Nerve Degeneration Neurons Normal tissue morphology Operative Surgical Procedures Optical Methods Optics Oxygen Patients Pattern Phase Prevention strategy Research Risk Factors Role Severities Severity of illness Stimulus Stroke Structure Surface System Techniques Therapeutic Thrombosis Tissues awake brain tissue cerebrovascular effective therapy flexibility hemodynamics high resolution imaging imaging system implantation improved innovation longitudinal animal study mouse model multimodality nanoelectronics neuroimaging neurophysiology neurovascular coupling novel optical imaging phosphorescence preventive intervention relating to nervous system response spatiotemporal stroke model stroke patient temporal measurement

项目摘要

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.

项目摘要：神经血管耦合，神经活动与血液动力学之间的紧密空间和临时关系调节代谢底物的递送以满足神经元激活的需求，对大脑的结构和功能完整性。它还构成了现代神经影像学技术的基础作为使用血流动力学反应来映射脑功能的fMRI。尽管它具有重要的基本性和临床重要性，血液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；脑血管的定量作用神经血管耦合及其对疾病严重程度和进展的疾病是研究了。这种知识差距对广泛应用的精确临床解释施加局限性神经影像学技术以及明确针对神经血管障碍的治疗机会耦合进行治疗。该项目的目的是提供空间解决的量化在健康和中风和高血压进展过程中，神经血管耦合。假设是可以通过应用新型慢性多模式平台来量化和跟踪神经血管耦合简单地绘制具有高空间和临时性的神经活动和血流动力学参数在行为动物的几周到几个月内解决。这是我们最近的小说发展所启用的超列出的纳米电子神经电极的类型，可提供空间分辨的神经活动记录无缝组织整合和慢性光学获取。我们将将这些电极与小说结合在一起功能性光学成像系统，简单地图像和量化全场脑血流和氧张力（PO2）。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，功能形式以及由于进展而引起的变化缺血，高血压和两者。该应用程序认为，该应用程序具有很高的创新性多个方面的综合技术进步，提供了高度新颖和强大的组合允许在以前无法实现的临时和空间中量化神经血管耦合的技术政权。该应用很重要，因为预计它将具有广泛的翻译重要性神经影像技术的精确临床解释以及脑血管干预已知神经血管耦合的疾病受到严重损害。这个长期目标项目是要了解中风和高血压中神经血管耦合的损害与人类患者发生的那些相似，以揭示高血压的机制中风的危险因素，并改善高血压中风患者的预防和干预策略。