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

基本信息

批准号：
10656378
负责人：
Randolph J. Nudo
金额：
$ 55.01万
依托单位：
UNIVERSITY OF KANSAS LAWRENCE
依托单位国家：
美国
项目类别：
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/10656378
关键词：
3-Dimensional Action Potentials Acute Alzheimer&apos 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 Implanted Electrodes Industry Ischemic Stroke Lateral Light Link Longitudinal Studies Macaca mulatta Maps Metabolic Marker Microelectrodes Modality Modeling Monitor Monkeys Morphologic artifacts Motion Motor Motor Cortex Neuroanatomy 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 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 neural neuroprotection nonhuman primate photoacoustic imaging post stroke preclinical study response sound stroke model stroke therapy success temporal measurement therapy development tool

项目摘要

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.

抽象的已建议将非人类灵长类动物（NHP）模型作为临床前的理想动物模型，中风治疗学术行业圆桌会议（楼梯）委员会的转化中风研究啮齿动物的翻译失败以及明显的脑血管，神经解剖和生物分子相似性在NHP和人类之间。为了应对这一建议，Nudo博士（当前建议的PI之一），在过去的几十年中，率先开发并进一步开发了NHP中风模型。虽然与临床相关现在可以使用NHP中风模型，成像方式的局限性可以在深处绘制神经激活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的功能变化。但是，该技术受到差的限制收集功能信息时的时间和空间分辨率。特别是，对于涉及的大脑研究醒着，行为活跃的猴子，fMRI的时间分辨率有限可能是一个重大障碍，因为运动伪影。另外，许多研究都使用慢性侵入性微电极植入物记录行动潜力和局部田间潜力在清醒猴子中；但是，微电极电记录非常侵入性，空间分辨率差，并且不提供深度分辨信息。我们建议基于新兴的光声（PA）开发可穿戴的全脑成像系统使用NHP模型进行缺血性中风研究的成像（PAI）。缺血性中风的特征是变化大脑中的血液动力学。由主要的脑动脉或其分支的阻塞触发的缺血性中风导致急性和慢性的脑血管适应。基于光吸收对比的PAI是对脑血流动力学的变化的本质敏感，包括血容量（灌注）和血液氧合（消耗氧）。因此，PAI具有出色的理解急性和慢性的能力中风后的脑血管适应以及功能激活导致的血液动力学变化大脑。建立在我们在PA脑成像方面的强大专业知识上恒河猴，我们建议开发一种可用于深层的实时可穿戴式PA脑成像系统大脑映射穿过颅窗。利用最先进的电容性微机械超声波换能器（CMUT）技术，拟议的PAI技术可以提供深度分辨的功能信息在深部大脑区域中，空间分辨率高。提出了两个目标：1）评估和优化可穿戴的多波长基于CMUT的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科学提供答案有关使用NHP模型的中风的问题，并为新的中风疗法开发铺平了道路。