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型系统，脊柱调查员TM，用于执行自动四维 (4D)三维（3D）显微镜下树突棘形态变化的定量分析 在不同时间点用体内多光子荧光显微镜获得的图像。树突状细胞的作用 脊髓是神经科学研究中最活跃和最重要的领域之一。树突棘的可塑性 形态学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中。 此外，许多复杂的大脑疾病，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、帕金森病、亨廷顿病、肌萎缩侧索硬化症和中风， 其特征在于树突棘病理学，包括异常树突棘密度和形态， 树突棘缺失和异常树突棘可塑性。虽然不可能研究 树突棘形态在人脑体内，有可能在小鼠模型中形成复杂的人脑 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奋进， 用于自动4D树突棘定量分析的工具是不可用的。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复制的结果， 符合NIH的严格和透明政策。脊柱调查员将帮助解决这一站不住脚的情况 with a number数of distinct独特innovations创新.具体而言，Spines Investigator将包括新技术， 能够自动比较树突棘形态在3D图像上的采集与体内 多光子荧光显微镜在小鼠大脑中的不同时间点的精确相同部位。 它还将使新的研究结合树突棘变化的4D体内定量分析， 形态学与淀粉样斑块的分析（在阿尔茨海默病），以及小胶质细胞和 星形胶质细胞为树突棘的自动化4D体内定量分析创建新的解决方案 形态学，脊柱研究者将建立在我们的Neurolucida 360 ®技术开发的第二阶段 (SBIR快速通道赠款MH 093011）。我们将把脊柱研究者培养成一个经过测试、验证、支持和 完整的文件系统。对神经科学研究界的好处，药理学和 生物技术的研究和发展，以及整个社会将更好地理解的关键作用， 在各种生理和病理条件下， 条件特别是，这将为开发新的治疗策略提供更好的基础， 复杂的脑部疾病