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: 10317128
• 负责人: Lan Luan
• 金额: $ 45.95万
• 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/10317128
• 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.

项目概要： 脑微梗塞与老年和受伤大脑的神经功能障碍有关 虽然有证据表明它们很普遍，但由于其体积小而经常逃避临床检测。 表明与较大的梗塞相比，微梗塞可能具有独特的时间过程和空间模式， 对同一大脑中的血流动力学和神经反应进行空间分辨的纵向跟踪尚未实现 之所以能够实现，很大程度上是由于缺乏能够量化多种神经生理学和 因此，在数周至数月的时间内具有足够空间分辨率的血流动力学参数。 个体或累积微梗塞的神经生理学后果，包括其时空 进化和长期结果仍然很大程度上未知，限制了我们识别和瞄准它们的能力 干预策略的长期目标是了解微梗塞的病理影响。 丰度、空间分布、发生时间和危险因素的变异性与人类患者相似。 该项目的目标是确定个体和累积的神经和血液动力学影响 小鼠模型中的脑微梗塞假设是微梗塞导致时空变化。 神经元损伤和血流动力学缺陷远远超出病变部位并持续到慢性时间 尺度，这需要对多个神经生理学参数进行空间解析和纵向跟踪 我们将使用两种类型的超灵活神经电极阵列，花费数周至数月的时间来揭示它们的全部影响。 用于空间分辨表面和皮质内记录，两者都与慢性光学兼容 我们将把神经记录与一组能够诱导目标微信号的光学系统结合起来。 控制大小、位置和发生时间的闭塞，并绘制和量化脑血流和 使用清醒的行为在全局视野和深度分辨的微观尺度上进行氧合。 动物，我们将 1）确定个体引起的血流动力学和神经变化之间的相关性 微梗塞，2) 绘制并跟踪受控病变大小的微梗塞的空间范围，以及 3) 确定 具有延迟发作时间的累积性微梗塞的血流动力学和神经影响。 申请人认为，它具有高度创新性，因为它集成了功能和功能方面的技术进步 成像和神经记录提供高度新颖和强大的组合，纵向允许， 对同一大脑区域中的多个神经生理学参数进行空间分辨量化，并允许 用于研究以前无法实现的微梗塞，该项目将提高人们的理解。 微梗塞的生理影响及其对各种神经功能障碍的影响 它们同时存在的神经退行性疾病和脑血管疾病，并提供了新的见解 干预的治疗时间窗口。