Whole-brain fluorescence and brightfield imaging at single-cell level

单细胞水平的全脑荧光和明场成像

• 批准号: 7801707
• 负责人: Lloyd John LaComb
• 金额: $ 49.29万
• 依托单位: DMETRIX, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7801707
• 关键词: Affect; Aging; Alzheimer' s Disease; American; Amyloid Proteins; Anatomy; Anti-Sense Probes; Area; Arizona; Arts; Award; Behavior; Biomedical Engineering; Brain; Brain imaging; Cells; Characteristics; Cognition; Color; Communities; Computer software; Confocal Microscopy; Coupled; Custom; Data; Data Base Management; Data Set; Databases; Detection; Development; Digoxigenin; Disabled Persons; Disease; Emotions; Engineering; Equipment; Fluorescence; Genes; Glass; Goals; Health; Hippocampus (Brain); Histology; Image; Image Analysis; Immediate-Early Genes; Individual; Institutes; Investigation; Knowledge; Label; Lateral; Lead; Licensing; Light Microscope; Market Research; Marketing; Measures; Medical Device; Mental Depression; Metadata; Microscope; Microscopic; Modeling; Mus; Neurophysiology - biologic function; Neurosciences; Neurosciences Research; Optics; Parkinson Disease; Pathology; Patients; Performance; Phase; Primates; Psychology; RNA; Radiology Specialty; Rattus; Reading; Research; Research Personnel; Resolution; Sales; Sample Size; Sampling; Scanning; Schizophrenia; Science; Scientist; Slide; Software Tools; Solutions; Speed; System; Technology; Temporal Lobe Epilepsy; Time; Tissues; Universities; Vendor; Work; Writing; base; brain tissue; college; cost; design; digital imaging; experience; flexibility; fluorescence imaging; imaging modality; innovation; instrument; instrumentation; interest; mouse model; nervous system disorder; nonhuman primate; normal aging; operation; product development; programs; prototype; public health relevance; research study; submicron; three-dimensional modeling

DESCRIPTION (provided by applicant): The goal of this project is to develop an open and flexible imaging platform capable of rapid, 0.5- 5 ¿m pixel resolution image capture of large-area histology sections (up to 125 mm by 175 mm), in brightfield and by epi-fluorescence optical sectioning. The project involves state-of-the- art instrumentation development coupled with application programming interfaces (APIs) to provide users with a reliable, multi-purpose research instrument. The development of a high speed large format imaging system will dramatically accelerate investigations such as amyloid protein studies for Alzheimer's disease or the expression of immediate-early genes (IEG) in understanding of the cellular basis of cognition. The number of digital-imaging system options decreases dramatically as the size of histology sections outgrows 1" W 3" glass slides. Further, because the current vendors are concentrating on digitizing anatomic pathology, their systems tend to be closed and inflexible to accommodate the regulatory constraints on medical devices. The market opportunity that DMetrix has identified is a robust and reliable commercial imaging platform with the flexibility and customization options valued by research groups. The project is divided into two Phases, punctuated by a demonstration of quantitative criteria, related to instrument and software performance. The primary goal of Phase I is the demonstration of feasibility of the large-area, rapid imaging instrument for brightfield and epi-fluorescence. A second goal is an image-viewer application that allows practical interaction with terabyte image data sets as will be generated by the instrument. The Specific Aims of Phase II are selected to lead to a product launch at the conclusion of the project. The Phase II Aims include the development of a "V6," six-imaging-module slide scanner, image- management software, and an advanced image-viewer application. Further, the work in Phase II leverages the core expertise of DMetrix, namely the development of fast, parallel image-capture instruments. A significant part of the Phase II effort will be directed at making the proposed instrument manufacturable at a minimum cost of goods sold (COGS) and optimized for serviceability. DMetrix has teamed on this project with an interdisciplinary group of academic experts from the University of Arizona. The University team includes Dr. Carol Barnes from the McKnight Brain Institute, Dr. Ted Trouard, Department of Radiology and Biomedical Engineering, and Dr. Gene Alexander, Director of the Brain Imaging, Behavior and Aging Lab in the Department of Psychology. These University of Arizona scientists represent a diverse sampling of the broad impact of the proposed imaging platform on neuroscience research. PUBLIC HEALTH RELEVANCE: Understanding the circuits in the brain responsible for cognition, emotion and action is a critical first step to developing treatments for important neurological disorders, such as Alzheimer's disease, Parkinson's disease, temporal lobe epilepsy, depression, and schizophrenia. Collectively, these disorders affect over 20 million Americans. Our long-range goal is to develop a system that has wide application across the field of neuroscience that will enable experiments impeded in the past by technological limitations, to span mouse models of disease to rat and nonhuman primate models of normal aging. This knowledge may bring us closer to optimizing neural function in health, and developing new therapies for patients disabled by neurological disease.

描述（由应用程序提供）：该项目的目的是在Brightfield和Epi-Fluorescence Optical Optical Sertaging中开发一个能够快速的，0.5-5的开放式成像平台，该平台能够快速，0.5-5。分辨率分辨率捕获大面积组织学部分（高达125 mm x 175 mm）。该项目涉及最新的仪器开发以及应用程序编程界面（API），为用户提供可靠的多功能研究工具。高速大格式成像系统的开发将大大加速研究，例如阿尔茨海默氏病的淀粉样蛋白研究或在理解认知细胞基础的情况下表达即时基因（IEG）。随着组织学部分的大小超过1“ W 3”载玻片，数字成像系统选项的数量会大大减少。此外，由于目前的供应商集中于数字化解剖病理学，因此它们的系统倾向于封闭且不灵活，以适应医疗设备上的调节限制。 DMetrix确定的市场机会是一个可靠且可靠的商业成像平台，其灵活性和自定义选项由研究小组重视。该项目分为两个阶段，并通过与仪器和软件性能有关的定量标准的演示进行了打击。第一阶段的主要目标是证明大面积，快速成像仪器的可行性，用于Brightfield和Epi荧光。第二个目标是图像视图应用程序，该应用程序允许与仪器生成的TRABYTE图像数据集进行实际交互。选择第二阶段的具体目标是在项目结束时导致产品推出。第二阶段的目的包括开发“ V6”，六成像模块幻灯片扫描仪，图像管理软件和高级图像视图应用程序。此外，第二阶段的工作利用了DMetrix的核心专家，即开发快速，平行的图像捕捉工具。第二阶段工作的很大一部分将致力于以最低销售商品（COG）成本制造拟议的仪器制造商，并为可使用。 DMetrix已与亚利桑那大学的一个跨学科的学术专家团队合作。大学团队包括来自McKnight Brain Institute的Carol Barnes博士，放射学和生物医学工程系的Ted Trouard博士以及心理学系的大脑成像，行为和老化实验室主任Gene Alexander博士。这些亚利桑那大学的科学家代表了潜水员对拟议成像平台对神经科学研究的广泛影响的采样。 公共卫生相关性：了解负责认知，情绪和动作的大脑中的电路是开发重要神经系统疾病的治疗方法的关键第一步，例如阿尔茨海默氏病，帕金森氏病，临时叶癫痫，抑郁症，抑郁症和精神分裂症。总的来说，这些疾病影响了超过2000万美国人。我们的远程目标是开发一个在整个现场神经科学中具有广泛应用的系统，该系统将通过技术局限性阻碍的实验，以将疾病的小鼠模型跨越大鼠和正常衰老的非人类私人模型。这些知识可能会使我们更接近优化健康中的神经元功能，并为神经系统疾病残疾的患者开发新的疗法。