Longitudinal multimodal mapping to decipher the neurovascular impact of microinfarcts

纵向多模态映射破译微梗塞对神经血管的影响

• 批准号: 10542275
• 负责人: Lan Luan
• 金额: $ 7.06万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10542275
• 关键词: Acute; Anesthesia procedures; Animal Model; Animals; Brain; Brain Injuries; Brain region; Cerebrovascular Circulation; Cerebrovascular Disorders; Chronic; Clinical; Detection; Electrodes; Electrophysiology (science); Event; Evolution; Functional Imaging; Goals; Histologic; Histology; Human; Image; Imaging Techniques; Impaired cognition; Impairment; Individual; Infarction; Intervention; Investigation; Lead; Lesion; Link; Location; Maps; Measurement; Methods; Microscopic; Microvascular Dysfunction; Neurodegenerative Disorders; Neurologic; Neurologic Dysfunctions; Neurons; Optical Methods; Optics; Outcome; Pathologic; Patients; Pattern; Physiological; Recording of previous events; Resolution; Risk Factors; Site; Spatial Distribution; Stroke; Surface; System; Techniques; Therapeutic; Time; Time Factors; Tissues; Work; aged; awake; cerebral microinfarct; clinically relevant; density; effective intervention; experimental study; flexibility; hemodynamics; implantation; improved; in vivo; innovation; insight; millimeter; mouse model; multimodality; neuroimaging; neurophysiology; neurovascular; novel; relating to nervous system; response; serial imaging; spatiotemporal; two-dimensional

PROJECT SUMMARY: Cerebral microinfarcts are in association with neurologic dysfunctions in aged and injured brain where they are found to be prevalent, but often escape clinical detection owing to their small sizes. Although evidence suggests that microinfarcts likely have a distinct time course and spatial pattern compared to larger infarcts, spatially-resolved, longitudinal tracking of both hemodynamic and neural responses in the same brain has not been realized, largely due to a lack of methods capable of quantifying multiple neurophysiological and hemodynamic parameters with sufficient spatial resolution over periods of weeks to months. As a result, the neurophysiological consequences of individual or cumulative microinfarcts, including their spatiotemporal evolution and long-term outcome, remain largely unknown, limiting our ability to identify and target them for intervention strategies. The long-term goal is to understand the pathological impacts of microinfarcts with variability in abundance, spatial distribution, occurrence time and risk factors similar to human patients. The objective of this project is to determine the neural and hemodynamic impact of individual and cumulative cerebral microinfarcts in a mouse model. The hypothesis is that microinfarcts lead to spatiotemporally varying neuronal impairment and hemodynamic deficits that extend well beyond the lesion site and into chronic time scales, which requires spatially resolving and longitudinal tracking of multiple neurophysiological parameters over weeks to months to reveal their full impacts. We will use two types of ultra-flexible neural electrode arrays for spatially-resolved surface and intracortical recording, both of which are compatible with chronic optical methods. We will combine neural recording with a set of optical systems that are able to induce targeted micro- occlusions with controlled size, location and onset time, and to map and quantify cerebral blood flow and oxygenation over a global field of view and at depth-resolved microscopic scales. Using awake, behaving animals, we will 1) determine the correlation between hemodynamic and neural changes induced by individual microinfarcts, 2) map and track the spatial extent of microinfarcts at controlled lesion sizes, and 3) determine the hemodynamic and neural impacts of cumulative microinfarcts with delayed onset time. The application is highly innovative, in the applicant’s opinion, because it integrates technical advancements on both functional imaging and neural recording to provide a highly novel and powerful combination that permits longitudinal, spatially resolved quantification of multiple neurophysiological parameters in the same brain region and allows for investigation of microinfarcts in previously unattainable regimes. The project will improve the understanding of the physiological impact of microinfarcts and their contribution to neurologic dysfunctions in a variety of neurodegenerative and cerebrovascular diseases that they coexist with, and provide new insight into the therapeutic time window for intervention.

项目摘要： 脑微感染与它们所在的衰老和受伤的大脑中的神经功能障碍相关 发现很普遍，但由于其小尺寸，经常逃脱临床检测。虽然证据 表明，与较大的Infacts相比，微感染可能具有不同的时间过程和空间模式， 同一大脑中血液动力学和神经反应的空间分辨，纵向跟踪尚未 被实现的，很大程度上是由于缺乏能够量化多重神经生理学和 在数周到几个月内具有足够空间分辨率的血液动力学参数。结果， 个体或累积微量信息的神经生理后果，包括其时空 进化和长期结局，在很大程度上未知，限制了我们识别和瞄准它们的能力 干预策略。长期目标是通过使用微观感染的病理影响 抽象，空间分布，发生时间和风险因素的变异性与人类患者类似。 该项目的目的是确定个体和累积的神经和血流动力学影响 小鼠模型中的脑微感染。假设是微感染导致空间暂时变化 神经元损伤和血流动力学定义远远超出病变部位并延伸到慢性时间 量表，需要在空间上解析和纵向跟踪多个神经生理参数 在数周到几个月的时间里，揭示了它们的全部影响。我们将使用两种类型的超芬兰神经电极阵列 用于空间分辨的表面和皮质内记录，两者都与慢性光学兼容 方法。我们将将神经元记录与一组能够诱导靶向微型的光学系统相结合 具有控制尺寸，位置和发病时间的闭塞，并绘制并量化脑血流和 在全球视野和深度分辨显微镜尺度上的氧合。使用清醒，行为 动物，我们将1）确定个体引起的血液动力学和神经变化之间的相关性 微量摄入量，2）在受控病变大小下绘制并跟踪微观摄影的空间范围，3）确定 累积微吸收时间的血液动力学和神经影响，发作时间延迟。该应用程序是 申请人认为，高度创新性，因为它将技术进步整合到两个功能上 成像和神经记录，提供了一种高度新颖和强大的组合，允许纵向， 在同一大脑区域的空间分辨量的多个神经生理参数，并允许 用于在以前无法实现的政权中进行微观侵入的投资。该项目将改善理解 微吸收的物理影响及其对各种神经功能障碍的贡献 它们与之共存的神经退行性和脑血管疾病，并提供了新的见解 干预的治疗时间窗口。