ShEEP Request for Ultrafast Ultrasound for Brain Imaging in Freely Behaving Animals

ShEEP 请求使用超快超声波对自由行为的动物进行脑成像

• 批准号: 9908895
• 负责人: Charles Kenneth Meshul
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908895
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The goal of this proposal is to establish a multi-user Brain Imaging Core at the VA Portland Health Care System facility (VAPORHCS) using ultrafast ultrasound in freely behaving animals. VAPORHCS has a long history of strong research within its facility, and currently has over 175 investigators and more than 570 active protocols. In 2018, Portland VA scientists produced nearly 500 research publications, were awarded over $33 million in research grants from the VA, NIH, DoD and other sources, and VAPORHCS ranks in the top 10 nationwide among VA Medical Centers in grant support from the Department of Veterans Affairs. Research is conducted in nearly ~100,000 square feet of wet and dry lab space that supports programs in basic science, clinical research, health services, cooperative studies, epidemiology and outcomes research. The VAPORHCS houses several funded neuroscience-related centers reflecting expertise in specific research areas, including: 1) NIH-funded Portland Alcohol Research Center (PARC), 2) National Center for Rehabilitative Auditory Research, 3) Mental Illness Research Education and Clinical Center, 4) Research Enhancement Awards Program in Multiple Sclerosis, 5) Parkinson's Disease Research Education and Clinical Center, 6) Multiple Sclerosis Center of Excellence, 7) Epilepsy Center of Excellence, 8) Hepatitis C Virus (HCV) Resource Center, 9) NIH-funded Methamphetamine Abuse Research Center, 10) VA Health Services Research and Development Center of Innovation (COIN), and 11) Agency for Healthcare Research and Quality Evidence Based Practice Center. The plan is to purchase the Ultrafast Ultrasound brain imaging system and to establish a core laboratory to service the needs of VA-funded scientists for brain imaging in freely behaving rodents. This request is for an instrument made by ICONEUS, the first and only developer of this novel technology, which will enable researchers to non-invasively acquire and tomographically reconstruct changes in cerebral blood flow perfusion to brain areas in coronal slices as well as 3D reconstruction of the whole brain. The technique has high temporal (100 frames per second) and spatial resolution (sub-millimeter range) and facilitates high throughput longitudinal study designs of the nature contemplated by Portland VA scientists. The technology offers an extremely powerful 3D in vivo screening method yielding quantitative and calibrated temporal and spatial/anatomical data while animals are fully awake and freely behaving in behavioral tasks of interest. Planned studies by the 8 VA-Funded PI's include: 1) Measure brain regions involved in chronic progressive MPTP model of Parkinsons disease in mice and response to treatments (Meshul), 2) Measure brain regions involved in alcohol-use disorder in mice and mechanisms of novel immunotherapies (Loftis), 3) Measure brain regions involved in mouse model of Alzheimer's disease and response to treatment with the botanical Centella asiatica (Quinn), 4) Measure brain regions involved in methamphetamine addiction in high and low administration mouse strains and mechanisms involving glutamatergic balance (Richards), 5) Measure brain regions involved in the Experimental Autoimmune Encephalitis model of multiple sclerosis in mice and response to treatments (Vandenbark), 6) Measure brain regions involved in post-traumatic epilepsy and control of seizure spread by opioids and other neuropeptides (Schnell), 7) Measure brain regions involved in sleep and cognitive deficits following TBI in mice and response to dietary intervention with branched chain amino acids (Lim), and 8) Measure brain regions involved in binge drinking and ethanol withdrawal (Ozburn).

该提案的目的是在VA波特兰医疗保健中建立多用户脑成像核心 系统设施（Vaporhcs）使用自由行为的动物中的超声超声。 Vaporhcs有很长的 其设施内有大量研究的历史，目前有175多名调查员和超过570个活跃 协议。 2018年，波特兰弗吉尼亚州科学家制作了近500名研究出版物，获得了33美元的授予 来自VA，NIH，DOD和其他来源的数百万美元赠款，以及Vaporhcs排名前10名 VA医疗中心在退伍军人事务部提供赠款支持中的全国。研究是 在近约100,000平方英尺的潮湿和干燥实验室空间中进行，该空间支持基础科学课程， 临床研究，卫生服务，合作研究，流行病学和结果研究。 Vaporhcs 房屋有几个资助的与神经科学相关的中心，这些中心反映了特定研究领域的专业知识，包括： 1）NIH资助的波特兰酒精研究中心（PARC），2）国家康复听觉中心 研究，3）精神疾病研究教育和临床中心，4）研究增强奖 多发性硬化症的计划，5）帕金森氏病研究教育和临床中心，6）多重 硬化症卓越中心，7）癫痫卓越中心，8）丙型肝炎病毒（HCV）资源中心， 9）NIH资助的甲基苯丙胺滥用研究中心，10）VA健康服务研究和 创新发展中心（硬币）和11）医疗保健研究机构 基于实践中心。 该计划是购买超声超声脑成像系统，并建立一个核心实验室 为VA资助​​的科学家的需求提供自由表现啮齿动物的大脑成像的需求。这个请求是 Iconeus制造的仪器，这是这项新技术的第一个也是唯一的开发人员，这将使 研究人员非侵入性获取和层压结构的脑血流变化 冠状切片中的大脑区域以及整个大脑的3D重建。该技术具有 高时间（每秒100帧）和空间分辨率（亚毫米范围），并促进 波特兰弗吉尼亚州科学家考虑的性质的吞吐量纵向研究设计。技术 提供非常强大的3D体内筛选方法，得出定量和校准的时间和 空间/解剖学数据完全清醒并且在感兴趣的行为任务中自由行为。 8 VA资助的PI的计划研究包括：1）测量涉及慢性进步的大脑区域 小鼠帕金森氏病的MPTP模型和对治疗的反应（Meshul），2）测量大脑区域 涉及小鼠酒精疾病和新型免疫疗法机制（loftis），3）测量大脑 涉及阿尔茨海默氏病小鼠模型的区域以及对植物心治疗的反应 亚洲（Quinn），4）测量与甲基苯丙胺成瘾有关的大脑区域 给药的小鼠菌株和涉及谷氨酸能平衡的机制（理查兹），5）测量大脑 小鼠和 对治疗的反应（Vandenbark），6）测量参与创伤后癫痫和对照的大脑区域 阿片类药物和其他神经肽（Schnell）的癫痫发作，7）测量参与睡眠和的大脑区域 TBI在小鼠中的认知缺陷以及对分支链氨基酸饮食干预的反应 （lim）和8）测量参与暴饮暴食和抽出乙醇的大脑区域（Ozburn）。