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.

项目概要 我们对神经精神疾病的理解正在经历从简单模型的范式转变 强调神经递质失衡，转向基于神经异常的更复杂的理论 电路功能。这对于理解精神分裂症和创伤后应激障碍 (PTSD) 等疾病尤其重要，这些疾病 无法用简单的生化解释来解释，但现在已知涉及神经系统的异常模式 活动。即使对于其他类型的脑部疾病，例如神经退行性疾病（例如帕金森病）， 或具有分子遗传、细胞或环境原因的神经发育障碍（例如自闭症）， 人们越来越认识到，功能障碍最终表现在神经回路水平上 大脑，并表现为异常的神经回路动力学。然而，我们仍然缺乏至关重要的基本认识 正常行为期间的神经活动模式以及这些模式在疾病中如何改变。许多啮齿动物 人类大脑疾病模型现已可用，但神经科学家仍因缺乏技术而受到阻碍 用于大规模记录和操纵大量基因识别神经元的活动 行为动物受试者的大脑。 Inscopix, Inc. 从斯坦福大学分离出来，将一种 微型荧光显微镜技术使神经科学家能够可视化高达 1200 的 Ca2+ 动态 神经元同时处于清醒状态，以细胞分辨率表现啮齿类动物的行为。商业的发展 nVista 系统的部分资金来自先前的 NIMH SBIR 拨款。该项目超出了所有人的预期 举例说明了 NIH/NIMH SBIR 计划如何高效地促进创新和支持 神经科学突破性创新的商业化。先前 SBIR 第一阶段和 第二阶段是 nVista 系统，目前已在全球 200 多个实验室使用，这导致 在顶级期刊上发表超过 50 篇科学论文。 在此快速通道提案中，我们将在之前成功的 SBIR 和 nVista 的成功基础上，开发 并将下一代脑图平台商业化，将 nVista 转变为多功能平台 集成单色和双色成像、体积成像和光遗传学刺激功能， 以及基于网络、云兼容的数据采集和控制。在第一阶段，我们将设计和制造 用于下一代脑图平台（目标 1）的新型显微镜原型以及 先进的视频数据采集和处理系统（目标2）。我们将验证这些的性能 原型并与一小群 beta 实验室进行首次体内实验（目标 3）。在第二阶段，我们 将制造 15 个完整的、用户友好的系统，结合第一阶段（目标 4）的反馈，并提供支持 图像处理和分析算法（目标 5）。我们将用更大的体量进行广泛的体内实验 一组测试站点来展示所有功能的科学价值（目标 6）。在第二阶段结束时，我们将有一个 新型微型显微镜系统，集成了单色和双色成像、体积成像和 光遗传学刺激功能，以及基于网络的数据采集和控制，可供大规模使用 神经科学界的生产和商业化。新产品将取代我们现有的产品 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 电路活动对大脑功能的影响。我们期望该新产品能够催化神经回路研究并成为 全球绘制大脑回路活动图和了解大脑活动的努力的核心。我们也 预计该产品将被大型研究中心和制药公司广泛采用，扩大应用范围 超越基础神经科学的应用到围绕理解脑疾病和 开发下一代治疗方法。