Automated 3D quantitative analysis of dendritic spines imaged with light microscopy

使用光学显微镜成像的树突棘的自动 3D 定量分析

• 批准号: 9356578
• 负责人: Paul Angstman
• 金额: $ 79.99万
• 依托单位: MICROBRIGHTFIELD, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-22 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9356578
• 关键词: Aging; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Animals; Area; Astrocytes; Biotechnology; Boston; Brain; Brain Diseases; Central Nervous System Diseases; Childhood; Classification; Collaborations; Communities; Complex; Computer software; Dendritic Spines; Development; Dimensions; Down Syndrome; Elements; Financial compensation; Four-dimensional; Fragile X Syndrome; Frequencies; General Hospitals; Germany; Goals; Grant; Hour; Human; Huntington Disease; Image; Institutes; Investigation; Lead; Learning; Life; Manuals; Maps; Massachusetts; Medical center; Medicine; Memory; Memory impairment; Microglia; Modeling; Morphologic artifacts; Morphology; Motion; Multiphoton Fluorescence Microscopy; Mus; Nervous System Physiology; Neuroglia; Neurologic; Neurology; Neurosciences; Neurosciences Research; New York; Parkinson Disease; Pathologic; Pathology; Pharmacology; Phase; Physiological; Play; Policies; Positioning Attribute; Prions; Production; Reproducibility; Research; Research Personnel; Rett Syndrome; Role; Schizophrenia; Senile Plaques; Shapes; Site; Small Business Innovation Research Grant; Societies; Stroke; System; Technology; Testing; Three-Dimensional Image; Time; United States National Institutes of Health; Universities; Validation; Vertebral column; autism spectrum disorder; base; brain dysfunction; density; developmental disease; improved; in vivo; innovation; light microscopy; medical schools; microscopic imaging; mouse model; neuropathology; new technology; novel; research and development; software development; time interval; tool; treatment strategy; usability

Abstract This project aims to develop a novel system, Spines InvestigatorTM, for performing automated four-dimensional (4D) quantitative analysis of changes in dendritic spine morphology on three-dimensional (3D) microscopic images acquired with in vivo multiphoton fluorescence microscopy at different time points. The role of dendritic spines is one of the most active and important areas of neuroscience research. Plasticity of dendritic spine morphology plays a crucial role throughout life - in development, aging, as well as in learning and memory. Also, many complex brain diseases, including autism spectrum disorders, schizophrenia, Down syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and stroke, are characterized by dendritic spine pathology including abnormal dendritic spine density and morphology, dendritic spine loss, and aberrant dendritic spine plasticity. While it is not possible to study the plasticity of dendritic spine morphology in the human brain in vivo, it is possible in mouse models of complex human brain diseases. However, the study of these mouse models remains a tedious and cumbersome endeavor because tools for automated 4D dendritic spine quantitative analysis are not available. Critical steps that are currently performed manually in such investigations may lead to faulty and irreproducible results, which does not conform with NIH's rigor and transparency policy. Spines Investigator will help solve this untenable situation with a number of distinct innovations. Specifically, Spines Investigator will comprise novel technology that enables the automated comparison of dendritic spine morphology on 3D images acquired with in vivo multiphoton fluorescence microscopy in the brain of a mouse at precisely the same site at different time points. It will also enable new research that combines 4D in vivo quantitative analysis of changes in dendritic spine morphology with the analysis of amyloid plaques (in Alzheimer's disease), as well as analysis of microglia and astrocytes . To create this new solution for automated 4D in vivo quantitative analysis of dendritic spine morphology, Spines Investigator will build upon our Neurolucida360® technology developed during Phase II (SBIR Fast-track Grant MH093011). We will develop Spines Investigator as a tested, validated, supported and fully documented system. The benefit for the neuroscience research community, pharmacological and biotechnological research and development, and society in general will be to better understand the critical role of the plasticity of dendritic spine morphology in the brain under various physiological and pathological conditions. In particular, this will result in an improved basis for developing novel treatment strategies for complex brain diseases.

摘要 该项目旨在开发一种新的系统，Spines Investigator TM，用于执行自动化的四维 (4)三维(3D)显微镜下树突棘形态变化的定量分析 体内多光子荧光显微镜在不同时间点采集的图像。树枝状细胞的作用 脊椎是神经科学研究中最活跃、最重要的领域之一。树突棘的可塑性 形态在整个生命过程中起着至关重要的作用--在发育、衰老以及学习和记忆方面。 此外，许多复杂的脑部疾病，包括自闭症谱系障碍，精神分裂症，唐氏综合症， 阿尔茨海默病、帕金森氏病、亨廷顿病、肌萎缩侧索硬化症和中风 以树突棘病理为特征，包括树突棘密度和形态异常， 树突棘缺失和树突棘可塑性异常。虽然不可能研究它的可塑性 在活体人脑中树突棘的形态，有可能在小鼠模型中复杂的人脑 疾病。然而，对这些小鼠模型的研究仍然是一项乏味和繁琐的努力，因为 目前还没有自动化的4D树突棘定量分析工具。目前正在采取的关键步骤 在这种调查中手动执行可能会导致错误和不可重现的结果，而这不会 符合美国国立卫生研究院的严格和透明政策。Spines Investigator将帮助解决这种站不住脚的情况 有许多独特的创新。具体地说，Spines Investigator将包含新技术， 能够在体内获取的3D图像上自动比较树突棘的形态 多光子荧光显微镜在不同时间点的同一地点的小鼠的大脑中。 这也将使结合4D活体定量分析树突棘变化的新研究成为可能 形态学与淀粉样斑块的分析(阿尔茨海默病)，以及小胶质细胞和 星形胶质细胞。为树突棘的自动化4D体内定量分析创建这一新的解决方案 形态，脊柱调查员将在我们第二阶段开发的NeuroLucida360®技术的基础上再接再厉 (SBIR快速通道赠款MH093011)。我们将把Spines Investigator开发为经过测试、验证、支持和 完整记录的系统。对神经科学研究界、药理学和 生物技术的研究和开发，将对广大社会更好地发挥关键作用 不同生理病理条件下脑内树突棘形态可塑性的研究 条件。特别是，这将改善制定新的治疗策略的基础。 复杂的脑部疾病。