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: 9255387
• 负责人: Paul Angstman
• 金额: $ 80万
• 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/9255387
• 关键词: Aging; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Animals; Area; Astrocytes; Boston; Brain; Brain Diseases; Central Nervous System Diseases; Childhood; Classification; Collaborations; Communities; Complex; Computer software; Dendritic Spines; Development; 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; Pathology; Phase; Physiological; Play; Policies; Positioning Attribute; Prions; Production; 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; Universities; Validation; Vertebral column; abstracting; autism spectrum disorder; base; 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.

抽象的 该项目旨在开发一种新型系统，即Spines Respejatortm，用于执行自动化的四维 （4D）在三维（3D）显微镜下树突状脊柱形态变化的定量分析 在不同时间点使用体内多光子荧光显微镜获得的图像。树突状的作用 刺是神经科学研究中最活跃，最重要的领域之一。树突状脊柱的可塑性 形态在整个生命中都起着至关重要的作用 - 在发展，衰老以及学习和记忆中。 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， 阿尔茨海默氏病，帕金森氏病，亨廷顿氏病，肌萎缩性侧索硬化和中风 以树突状脊柱病理为特征，包括异常的树突状脊柱密度和形态， 虽然不可能研究 体内人脑中的树突状脊柱形态，在复杂人脑的小鼠模型中可能有可能 疾病。但是，对这些鼠标模型的研究仍然是一种繁琐而繁琐的努力，因为 自动4D树突状脊柱定量分析的工具不可用。当前的关键步骤 在此类投资中手动执行可能会导致错误和不可否认的结果，这不会 符合NIH的严格和透明政策。刺调查员将帮助解决这种站不住脚的情况 有许多不同的创新。具体而言，棘突调查员将完成新技术 在体内获得的3D图像上的树突状脊柱形态的自动比较可以自动比较 在不同时间点，小鼠大脑中小鼠大脑中的多光子荧光显微镜。 它还将实现新的研究，将树突状脊柱变化的4D在体内定量分析结合在一起 形态学分析淀粉样蛋白斑（在阿尔茨海默氏病中），以及小胶质细胞和分析 星形胶质细胞。为树突状脊柱的体内定量分析创建这种新解决方案 形态学，Spines研究者将建立在我们在II期期间开发的Neurolucida360®技术的基础上 （SBIR快速轨道授予MH093011）。我们将开发刺刺调查员作为经过测试，验证，支持的，并且 完全记录的系统。神经科学研究界的好处，药物和 生物技术研究与发展，整个社会将更好地了解关键作用 在各种生理和病理学下，大脑中树突状脊柱形态的可塑性 状况。特别是，这将为开发新的治疗策略的基础，以改善 复杂的大脑疾病。