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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：
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
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/10452501
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 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

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.

摘要