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

基本信息

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
项目类别：
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&apos 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

项目摘要

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颖的系统 Spines InvestigatorTM，用于执行自动化四维 (4D)三维(3D)显微镜下树突棘形态变化的定量分析使用体内多光子荧光显微镜在不同时间点获取的图像。树突棘的可塑性是神经科学研究最活跃和最重要的领域之一。形态学在整个生命过程中发挥着至关重要的作用——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、帕金森病、亨廷顿病、肌萎缩侧索硬化症和中风是以树突棘病理学为特征，包括异常的树突棘密度和形态，树突棘损失和异常树突棘可塑性虽然不可能研究树突棘的可塑性。人脑体内的树突棘形态，在复杂人脑的小鼠模型中是可能的然而，对这些小鼠模型的研究仍然是一项乏味且麻烦的工作，因为目前还没有用于自动 4D 树突棘定量分析的工具。在此类调查中手动执行可能会导致错误和不可重现的结果，这不会符合 NIH 严格和透明政策的 Spines Investigator 将有助于解决这一难以为继的情况。具体来说，Spines Investigator 将包含多项独特的创新技术。能够自动比较体内 3D 图像上的树突棘形态多光子荧光显微镜在小鼠大脑的不同时间点的同一部位进行观察。它还将使结合树突棘变化的 4D 体内定量分析的新研究成为可能通过淀粉样斑块分析（阿尔茨海默病）进行形态学分析，以及小胶质细胞和创建用于树突棘自动 4D 体内定量分析的新解决方案。 Spines Investigator 将基于我们在第二阶段开发的 Neurolucida360® 技术（SBIR 快速通道拨款 MH093011）我们将开发 Spines Investigator 作为经过测试、验证、支持和支持的工具。完整记录的系统对神经科学研究界、药理学和生物技术研究和开发以及整个社会将更好地理解其关键作用不同生理和病理条件下大脑树突棘形态的可塑性研究特别是，这将为开发新的治疗策略奠定基础。复杂的脑部疾病。