Next generation in vivo miniature microscopes integrating dual-color imaging, 3D imaging, and optogenetic stimulation with a cloud-compatible data acquisition platform

下一代体内微型显微镜将双色成像、3D 成像和光遗传学刺激与云兼容的数据采集平台集成在一起

• 批准号: 10292908
• 负责人: Kunal Ghosh
• 金额: $ 59.8万
• 依托单位: INSCOPIX, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10292908
• 关键词: Address; Adopted; Adoption; Algorithmic Analysis; Animals; Awareness; BRAIN initiative; Behavior; Behavioral; Biochemical; Biotechnology; Brain; Brain Diseases; Brain Mapping; Calcium; Cells; Cloud Computing; Color; Communities; Computer software; Contralateral; Data; Data Analyses; Data Compression; Data Set; Development; Disease; Electrophysiology (science); Elements; Equipment; Feedback; Functional disorder; Funding; Goals; Grant; Head; Heart; Image; Image Analysis; Individual; Journals; Laboratories; Lead; Link; Maps; Mechanics; Microscope; Modeling; Molecular Genetics; Monitor; National Institute of Mental Health; Nature; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurons; Neurosciences; Neurotransmitters; Online Systems; Optics; Outcome; Output; Parkinson Disease; Pattern; Performance; Phase; Play; Polychlorinated Biphenyls; Population; Post-Traumatic Stress Disorders; Process; Production; Psyche structure; Publications; Reporting; Research; Research Personnel; Resolution; Rodent; Rodent Model; Schizophrenia; Scientist; Signal Transduction; Site; Small Business Innovation Research Grant; Somatosensory Cortex; Speed; Stream; System; Technology; Testing; Therapeutic; Three-Dimensional Imaging; Time; United States National Institutes of Health; Universities; Vision; Visualization; autism spectrum disorder; awake; base; cloud based; cloud platform; cloud storage; commercialization; computerized data processing; data acquisition; data analysis pipeline; data quality; data streams; design; expectation; experience; experimental study; fluorescence microscope; human model; image processing; imaging capabilities; in vivo; in vivo imaging; innovation; large datasets; lens; manufacturability; miniaturize; multimodal data; neural circuit; neural patterning; neuropsychiatric disorder; next generation; novel; optogenetics; programs; prototype; relating to nervous system; secondary analysis; sensor; success; technological innovation; theories; user-friendly; web based interface; web-enabled

Project Summary Our understanding of neuropsychiatric disorders is undergoing a paradigm shift away from simple models emphasizing neurotransmitter imbalance towards more sophisticated theories based on abnormalities in neural circuit function. This is especially important for understanding disorders like Schizophrenia and PTSD, which defy simple biochemical explanations, but are now known to involve abnormal patterns of neural ensemble activity. Even for other types of brain disorders such as neurodegenerative disorders (e.g. Parkinson's Disease), or neurodevelopmental disorders (e.g. Autism) that have molecular-genetic, cellular or environmental causes, there is increasing awareness that the dysfunction is ultimately expressed at the level of neural circuits in the brain, and manifests in abnormal neural circuit dynamics. However, we still lack crucial basic understanding of neural activity patterns during normal behavior and how these patterns are altered in disease. Many rodent models of human brain diseases are now available, but neuroscientists are still hindered by lack of a technology for large-scale recording and manipulation of activity in large populations of genetically identified neurons in the brains of behaving animal subjects. Inscopix, Inc. was spun out of Stanford University to commercialize a miniature fluorescence microscope technology to enable neuroscientists to visualize Ca2+ dynamics in up to 1200 neurons simultaneously in awake, behaving rodents at cellular resolution. The development of the commercial system, nVista, was partly funded by a prior NIMH SBIR grant. The project surpassed all expectations and exemplifies how the NIH/NIMH SBIR program is highly effective in catalyzing innovation and supporting commercialization of breakthrough innovations for Neuroscience. The outcome of the prior SBIR Phase I and Phase II is an nVista system that is today in use at over 200 laboratories around the world and that has led to >50 scientific publications in top-tier journals. In this Fast-Track proposal, we will build on the prior successful SBIR and the success of nVista, and develop and commercialize a next generation brain mapping platform that transforms nVista into a versatile platform integrating single- and dual-color imaging, volumetric imaging, and optogenetics stimulation capabilities, together with web-based, cloud-compatible data acquisition and control. In Phase I, we will design and fabricate prototypes of the new microscope for the next generation brain mapping platform (Aim 1) together with an advanced video data acquisition and processing system (Aim 2). We will validate performance of these prototypes and conduct the first in vivo experiments with a small group of beta labs (Aim 3). In Phase II, we will fabricate 15 complete, user-friendly systems, incorporating feedback from Phase I (Aim 4), with supporting image processing and analysis algorithms (Aim 5). We will perform extensive in vivo experiments with a larger set of beta sites to demonstrate the scientific value of all features (Aim 6). At the end of Phase II, we will have a new miniature microscope system that integrates single- and dual-color imaging, volumetric imaging, and optogenetics stimulation capabilities, together with web-based data acquisition and control ready for mass production and commercialization to the Neuroscience community. The new product will obsolete our current nVista and will become our flagship product enabling brain researchers around the world to causally link neural circuit activity to brain function. We expect the new product to catalyze neural circuit research and to become a centerpiece of worldwide efforts to map brain circuit activity and to understand the brain in action. We also expect the product to be broadly adopted by large research centers and by Pharma, expanding the range of applications beyond basic Neuroscience to translational projects built around understanding brain disease and developing next generation treatments.

项目摘要 我们对神经精神疾病的理解正在经历与简单模型的转变 强调基于神经异常的神经递质对更复杂的理论的不平衡 电路功能。这对于理解精神分裂症和PTSD等疾病尤其重要， 反对简单的生化解释，但现在已知涉及神经合奏的异常模式 活动。即使对于其他类型的脑疾病，例如神经退行性疾病（例如帕金森氏病）， 或神经发育障碍（例如自闭症），具有分子遗传，细胞或环境原因， 人们越来越认识到功能障碍最终以神经回路的水平表达 大脑，表现出异常的神经回路动力学。但是，我们仍然缺乏对 正常行为期间的神经活动模式以及这些模式如何改变疾病。许多啮齿动物 现在可以使用人脑疾病的模型，但是由于缺乏技术，神经科学家仍然受到阻碍 用于大规模记录和操纵活动中大量遗传鉴定的神经元的活动 行为动物受试者的大脑。 Inscopix，Inc。从斯坦福大学开发，以商业化 微型荧光显微镜技术使神经科学家能够可视化CA2+动力学多达1200 神经元同时在清醒中，在细胞分辨率下表现啮齿动物。广告的发展 System，NVISTA，部分由先前的NIMH SBIR赠款资助。该项目超过了所有期望， 体现了NIH/NIMH SBIR计划如何在催化创新和支持方面非常有效 神经科学突破性创新的商业化。先前的SBIR I期和 第二阶段是一种NVISTA系统，如今已在全球200多个实验室中使用，这导致了 >顶级期刊中的50个科学出版物。 在这个快速提议中，我们将建立在先前的成功的SBIR和NVISTA成功的基础上，并发展 并将下一代大脑映射平台商业化，该平台将NVISTA转换为多功能平台 整合单色和双色成像，体积成像和光遗传学刺激能力， 与基于Web的云兼容数据采集和控制一起。在第一阶段，我们将设计和制造 下一代大脑映射平台的新显微镜的原型（AIM 1）以及一个 高级视频数据采集和处理系统（AIM 2）。我们将验证这些表现 原型并使用一小部分β实验室进行了第一个体内实验（AIM 3）。在第二阶段，我们 将制造15个完整的，用户友好的系统，结合了I阶段的反馈（AIM 4），并支持 图像处理和分析算法（AIM 5）。我们将在较大的体内实验进行广泛的体内实验 一组Beta站点以证明所有功能的科学价值（AIM 6）。在第二阶段结束时，我们将有一个 新的微型显微镜系统，该系统整合单色成像，体积成像以及 光遗传学刺激能力，以及基于Web的数据采集和控制能力 神经科学社区的生产和商业化。新产品将过时我们的当前 NVISTA并将成为我们的旗舰产品，使世界各地的大脑研究人员能够将神经联系起来 电路活动到大脑功能。我们希望新产品能够催化神经回路研究并成为 全球努力绘制脑电路活动并了解动作中的大脑的核心。我们也是 期望该产品由大型研究中心和制药公司广泛采用，扩大了 基本神经科学超出基本神经科学的应用，围绕理解脑疾病和 开发下一代治疗。