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: 8541687
• 负责人: Pixuan Zhou
• 金额: $ 79.11万
• 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 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8541687
• 关键词: Affect; Aging; Alzheimer' s Disease; American; Amyloid Proteins; Anatomy; Anti-Sense Probes; Area; Arizona; 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（由申请人提供）：本项目的目标是开发一种开放且灵活的成像平台，能够在明场和落射荧光光学切片中快速捕获大面积组织学切片（高达125 mm × 175 mm）的0.5- 5 μ m像素分辨率图像。该项目涉及最先进的仪器开发，加上应用程序编程接口（API），为用户提供可靠的多用途研究仪器。高速大幅面成像系统的发展将大大加速研究，如阿尔茨海默病的淀粉样蛋白研究或认知细胞基础的即刻早期基因（IEG）的表达。随着组织切片的尺寸超过1”W 3”载玻片，数字成像系统的选择数量急剧减少。此外，由于当前的供应商专注于解剖病理学的数字化，因此他们的系统往往是封闭的和不灵活的，以适应对医疗设备的监管约束。DMeetron已经确定的市场机会是一个强大而可靠的商业成像平台，具有研究小组所重视的灵活性和定制选项。该项目分为两个阶段，并不时演示与仪器和软件性能相关的定量标准。第一阶段的主要目标是证明大面积，快速成像仪器的明场和落射荧光的可行性。第二个目标是一个图像浏览器的应用程序，允许实际的互动与TB的图像数据集将产生的仪器。选择第二阶段的具体目标是为了在项目结束时推出产品。第二阶段的目标包括开发一个“V6”、六个成像模块的载玻片扫描仪、图像管理软件和一个高级图像查看器应用程序。此外，第二阶段的工作利用了DMeacon的核心专长，即开发快速、并行的图像捕获仪器。第二阶段工作的一个重要部分将是使拟议的仪器以最低的商品销售成本（COGS）制造，并优化其适用性。DMeetry与亚利桑那大学的一个跨学科学术专家小组合作开展了这个项目。大学团队包括来自麦克奈特大脑研究所的卡罗尔巴恩斯博士，放射学和生物医学工程系的泰德·特劳尔德博士，以及心理学系大脑成像、行为和衰老实验室主任吉恩·亚历山大博士。这些亚利桑那大学的科学家代表了拟议的成像平台对神经科学研究的广泛影响的不同样本。 公共卫生关系：了解大脑中负责认知、情感和行动的回路是开发重要神经系统疾病治疗方法的关键第一步，这些疾病包括阿尔茨海默病、帕金森病、颞叶癫痫、抑郁症和精神分裂症。总的来说，这些疾病影响了2000多万美国人。我们的长期目标是开发一种在神经科学领域具有广泛应用的系统，使过去因技术限制而受阻的实验能够跨越疾病的小鼠模型到正常衰老的大鼠和非人类灵长类动物模型。这些知识可能使我们更接近于优化健康的神经功能，并为神经系统疾病致残的患者开发新的疗法。