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).

本提案的目标是在VA波特兰医疗保健中心建立多用户脑成像核心 系统设施（VAPORHCS）在自由行为动物中使用超快超声。VAPORHCS有一个很长的 在其设施内强大的研究历史，目前有超过175名研究人员和570多名活跃的 协议. 2018年，波特兰弗吉尼亚州的科学家们发表了近500篇研究论文，获得了超过33美元的奖金。 来自VA，NIH，DoD和其他来源的研究赠款为100万美元，VAPORHCS排名前10位 在退伍军人事务部的资助下，全国范围内的退伍军人医疗中心。研究是 在支持基础科学项目的近10万平方英尺的干湿实验室空间中进行， 临床研究、卫生服务、合作研究、流行病学和成果研究。蒸汽 拥有几个资助的神经科学相关中心，反映了特定研究领域的专业知识，包括： 1)美国国立卫生研究院资助的波特兰酒精研究中心（PARC），2）国家反射听觉中心 研究，3）精神疾病研究教育和临床中心，4）研究促进奖 多发性硬化症项目，5）帕金森病研究教育和临床中心，6）多个 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)美国国立卫生研究院资助的甲基苯丙胺滥用研究中心，10）弗吉尼亚州卫生服务研究和 创新发展中心（COIN）和11）医疗保健研究和质量证据机构 基于实践中心。 该计划是购买超快超声脑成像系统，并建立一个核心实验室， 服务于VA资助的科学家对自由行为啮齿动物大脑成像的需求。此请求是针对 ICONEUS是这项新技术的第一个也是唯一的开发者， 研究人员非侵入性地获取和断层重建脑血流的变化， 冠状面脑区灌注以及全脑三维重建。该技术具有 高时间（每秒100帧）和空间分辨率（亚毫米范围）， 吞吐量纵向研究设计的性质所设想的波特兰弗吉尼亚州的科学家。技术 提供了一种非常强大的3D体内筛选方法， 空间/解剖数据，而动物完全清醒并在感兴趣的行为任务中自由行动。 由8名VA资助的PI计划进行的研究包括：1）测量参与慢性进展性脑梗死的脑区 小鼠中帕金森病的MPTP模型和对治疗的反应（Meshul），2）测量脑区域 参与小鼠酒精使用障碍和新型免疫疗法的机制（Loftis），3）测量大脑 阿尔茨海默病小鼠模型中涉及的区域和对植物性积雪草治疗的反应 asiatica（Quinn），4）测量高和低浓度甲基苯丙胺成瘾的大脑区域 给药小鼠品系和涉及代谢能平衡的机制（理查兹），5）测量脑 参与小鼠多发性硬化症的实验性自身免疫增强模型的区域， 对治疗的反应（Vandenbark），6）测量涉及创伤后癫痫和控制的脑区域 阿片类药物和其他神经肽传播的癫痫发作（Schnell），7）测量参与睡眠的大脑区域， TBI后小鼠的认知缺陷和对支链氨基酸饮食干预的反应 (Lim)和8）测量涉及狂饮和乙醇戒断的脑区域（Ozburn）。