Wearable real-time functional brain mapping for a non-human primate stroke model

用于非人类灵长类中风模型的可穿戴实时功能性大脑绘图

• 批准号: 10452501
• 负责人: Randolph J. Nudo
• 金额: $ 57.06万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10452501
• 关键词: 3-Dimensional; Action Potentials; Acute; Alzheimer' s Disease; Animal Behavior; Animal Model; Animals; Area; Autopsy; Behavior; Behavioral; Blood; Blood Volume; Blood flow; Brain; Brain Mapping; Brain imaging; Brain region; Cause of Death; Cephalic; Chronic; Development; Disease; Epilepsy; Failure; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Human; Image; Imaging technology; Implant; Industry; Ischemic Stroke; Lateral; Light; Link; Longitudinal Studies; Macaca mulatta; Maps; Metabolic Marker; Microelectrodes; Modality; Modeling; Monitor; Monkeys; Morphologic artifacts; Motion; Motor; Motor Cortex; Optics; Outcome; Oxygen Consumption; Parkinson Disease; Perfusion; Pharmaceutical Preparations; Play; Pre-Clinical Model; Process; Real-Time Systems; Recommendation; Recovery; Research; Resolution; Rodent; Role; Stroke; Surface; System; Techniques; Technology; Thalamic structure; Time; Training; Translating; Ultrasonic Transducer; United States; United States National Institutes of Health; Vascular remodeling; Visualization; absorption; awake; base; brain research; cerebral artery; cerebrovascular; clinically relevant; cost; design; disability; efficacious treatment; hemodynamics; imaging approach; imaging modality; imaging platform; imaging probe; imaging system; in vivo; method development; nonhuman primate; photoacoustic imaging; post stroke; preclinical study; relating to nervous system; response; sound; stroke model; stroke therapy; success; temporal measurement; therapy development; tool

ABSTRACT Non-human primate (NHP) models have been recommended as ideal animal models for preclinical, translational stroke research by the Stroke Therapy Academic Industry Roundtable (STAIR) committee due to translational failures in rodents and significant cerebrovascular, neuroanatomical and biomolecular similarities between NHPs and humans. In response to this recommendation, Dr. Nudo (one of PIs on the current proposal), has pioneered and further developed NHP stroke models in the past few decades. Although clinically-relevant NHP stroke models are now available, limitations in imaging modalities that can map neural activates in deep brains of awake monkeys are hindering the current research. Functional magnetic resonance imaging (fMRI) has been widely used to detect functional changes in the brain. However, this technique is limited by poor temporal and spatial resolution when collecting functional information. Particularly, for brain research involving awake, behaviorally active monkeys, the limited temporal resolution of fMRI can be a significant barrier because of motion artifacts. Alternatively, many studies have used chronic, invasive microelectrode implants for recording action potential and local field potentials in awake monkeys; however, microelectrode electrical recording is quite invasive, has poor spatial resolution, and does not provide depth-resolved information. We propose to develop a wearable, whole brain imaging system based on the emerging photoacoustic (PA) imaging (PAI) for ischemic stroke research with NHP models. Ischemic stroke is characterized by changes in hemodynamics in the brain. Triggered by the occlusion of a major cerebral artery or its branches, ischemic stroke leads to cerebrovascular adaptations both acutely and chronically. PAI, based on optical absorption contrast, is intrinsically sensitive to the changes in brain hemodynamics including both blood volume (perfusion) and blood oxygenation (oxygen consumption). Therefore, PAI offers excellent ability to understand the acute and chronic cerebrovascular adaption after stroke, as well as hemodynamic changes resulting from functional activation in the brain. Built on our strong expertise in PA brain imaging, especially in PAI of an awake behaviorally active rhesus monkey, we propose to develop a real-time wearable PA brain imaging system that can be used for deep brain mapping through a cranial window. By utilizing state-of-the-art capacitive micromachined ultrasonic transducer (CMUT) technology, the proposed PAI technology can provide depth-resolved functional information in deep brain regions in real-time with high spatial resolution. Two aims are proposed: 1) Evaluate and optimize a wearable, multi-wavelength CMUT-based PAI system for real-time visualization of functional activation in the NHP brain; and 2) Image changes in brain functional activations and cerebrovascular adaptations in an NHP stroke model in a longitudinal study. The success of this study will provide answers to important scientific questions about stroke with NHP models, and pave the way for new stroke therapy development.

抽象的 非人灵长类动物（NHP）模型已被推荐为临床前、 中风治疗学术产业圆桌会议 (STAIR) 委员会的转化性中风研究 啮齿类动物的翻译失败以及显着的脑血管、神经解剖学和生物分子相似性 NHP 和人类之间。为了回应这一建议，Nudo 博士（当前提案的 PI 之一）， 在过去的几十年里，开创并进一步发展了 NHP 中风模型。尽管与临床相关 NHP 中风模型现已可用，但成像方式的局限性无法绘制深层神经活动图 清醒猴子的大脑正在阻碍当前的研究。功能磁共振成像 (fMRI) 已被广泛用于检测大脑功能变化。然而，该技术受到较差的限制 收集功能信息时的时间和空间分辨率。特别是对于涉及大脑的研究 对于清醒、行为活跃的猴子来说，功能磁共振成像有限的时间分辨率可能是一个重大障碍，因为 运动伪影。或者，许多研究使用慢性、侵入性微电极植入来记录 清醒猴子的动作电位和局部场电位；然而，微电极电记录相当 侵入性，空间分辨率差，并且不提供深度分辨信息。 我们建议开发一种基于新兴光声（PA）的可穿戴全脑成像系统 使用 NHP 模型进行缺血性中风研究的成像 (PAI)。缺血性中风的特点是 大脑中的血流动力学。由大脑大动脉或其分支闭塞引发，缺血性中风 导致脑血管的急性和慢性适应。 PAI，基于光吸收对比， 对大脑血流动力学的变化（包括血容量（灌注）和血液）本质上敏感 氧合（耗氧量）。因此，PAI 提供了了解急性和慢性疾病的卓越能力。 中风后的脑血管适应，以及功能激活引起的血流动力学变化 大脑。建立在我们在 PA 脑成像方面的强大专业知识之上，特别是在清醒行为活跃的 PAI 方面 恒河猴，我们建议开发一种实时可穿戴 PA 脑成像系统，可用于深度 通过颅窗绘制大脑图。通过利用最先进的电容式微机械超声波 传感器（CMUT）技术，提出的PAI技术可以提供深度分辨的功能信息 具有高空间分辨率的实时大脑深部区域。提出两个目标：1）评估和优化 基于 CMUT 的可穿戴多波长 PAI 系统，用于实时可视化功能激活 NHP 大脑； 2) NHP 中大脑功能激活和脑血管适应的图像变化 纵向研究中的中风模型。这项研究的成功将为重要的科学问题提供答案 关于 NHP 模型中风的问题，并为新中风治疗的发展铺平道路。