ClearScope

清晰范围

基本信息

批准号：
10159328
负责人：
JACOB R GLASER
金额：
$ 96.99万
依托单位：
MICROBRIGHTFIELD, LLC
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10159328
关键词：
3-Dimensional Address Adoption Animal Model Area Axon Behavioral Research Benchmarking Biotechnology Brain Brain Diseases Brain imaging Collaborations Communities Complex Computer software Confocal Microscopy Data Set Dendrites Dendritic Spines Detection Development Human Image Immersion Lateral Legal patent Light Lighting Literature Methods Michigan Microscope Microscopy Mus National Institute of Mental Health Neurologic Neurons Neurosciences Research New York Optics Pattern Performance Pharmacology Phase Photobleaching Phototoxicity Preparation Process Production Rattus Refractive Indices Research Resolution Societies Specimen Speed Structure Subcellular structure System Techniques Technology Testing Thick Three-Dimensional Image Tissues Transgenic Animals Translations Universities Validation Varicosity base brain research design ex vivo imaging improved in vivo innovation insight microscopic imaging multiphoton microscopy neural network neuropsychiatry new technology nonhuman primate novel prototype research and development tool treatment strategy usability user-friendly

项目摘要

Combined in vivo and ex vivo three-dimensional (3D) whole-brain imaging of non-transgenic and transgenic animal models holds the promise of novel insights into neural network connectivity patterns. With regard to ex vivo light microscopic imaging of 3D whole-brain datasets, the best approach is brain clearing followed by whole-brain light sheet microscopy (LSM) because of its unique combination of speed, 3D resolving power, and low phototoxicity compared to confocal and multiphoton microscopy. Unlike other methods, the combined brain clearing / LSM approach makes it possible to use intact tissue and retain all intracellular connections within the brain structure. However, LSM systems commercially available are not suitable for ex vivo light microscopic imaging of 3D whole-brain datasets in advanced connectomics research. Recently, Dr. Raju Tomer (Dept. Biol. Sci., Columbia Univ., New York, NY) developed light sheet theta microscopy (LSTM), essentially a unique arrangement of two light sheets oblique to the specimen and one detection objective perpendicular to the specimen. This novel microscope is the basis for a number of capabilities in LSTM that are not all available with any other commercially available LSM systems. The LSTM technology has distinct advantages over confocal and other light sheet microscopes, including the unmatched ability to image thicker tissue specimens over a larger lateral area (XY) at higher optical resolutions, while maintaining fast imaging speed, high imaging quality, and low photo-bleaching. This promising technology serves as the basis for this Lab to Marketplace proposal to develop the ClearScope™, which refines and improves Dr. Tomer's original LSTM system to create a successful commercial microscope for wide-spread adoption. The key technical objectives for developing the ClearScope as a commercial product include creating and testing (i) a ClearScope prototype based on an optimized microscope hardware design; (ii) novel microscope hardware components for the ClearScope, comprising a novel chamber that contains the investigated specimen and the immersion medium, and a novel detection objective changer; (iii) novel control and image acquisition software for the ClearScope; and importantly, (iv) novel software that surpasses the existing state-of-the-art technology to assemble acquired image stacks into large 3D image volumes exceeding 10TB without need to downsample the image information. The production version of the ClearScope will benefit the neuroscience research community, pharmacological and biotechnological R&D, and society in general by improving understanding of neural network connectivity patterns as well as the neuropathological underpinnings of the large-scale connectional alterations associated with human neuropsychiatric and neurological conditions. In particular, this will result in an improved basis for developing novel treatment strategies for complex brain diseases.

非转基因和离体联合体内和离体三维 (3D) 全脑成像转基因动物模型有望为神经网络连接模式提供新的见解。对于 3D 全脑数据集的离体光显微成像，最好的方法是大脑透明化之后进行全脑光片显微镜 (LSM)，因为其独特的组合与共焦和多光子显微镜相比，速度快、3D 分辨率高、光毒性低。与其他方法不同，结合脑清除/LSM 方法可以使用完整的组织并保留大脑结构内的所有细胞内连接然而，LSM 系统商业化。现有的不适合先进的 3D 全脑数据集的离体光学显微成像最近，Raju Tomer 博士（纽约州哥伦比亚大学生物科学系）开发了光片θ显微镜（LSTM），本质上是两个光片的独特排列倾斜于样本和一个垂直于样本的检测物镜这一新颖的。显微镜是 LSTM 中许多功能的基础，而其他任何功能都无法提供这些功能。商用LSM系统与共焦和LSTM技术相比具有明显的优势。其他光片显微镜，包括在较厚的组织样本上成像的无与伦比的能力更高光学分辨率下更大的横向面积（XY），同时保持快速成像速度、高成像质量和低光漂白这一有前景的技术是该实验室的基础。开发 ClearScope™ 的市场提案，该提案改进并改进了 Tomer 博士的原创产品 LSTM 系统是打造成功的商用显微镜并得到广泛采用的关键技术。将 ClearScope 开发为商业产品的目标包括创建和测试 (i) 基于优化的显微镜硬件设计的 ClearScope 原型 (ii) 新型显微镜； ClearScope 的硬件组件，包括一个新颖的腔室，其中包含所研究的样本和浸没介质，以及新颖的检测物镜变换器；(iii)新颖的控制和 ClearScope 的图像采集软件；并且重要的是，(iv) 超越以往的新颖软件现有最先进的技术可将采集的图像堆栈组装成大型 3D 图像体积超过 10TB，无需对图像信息进行下采样。 ClearScope 将有利于神经科学研究界、药理学和生物技术领域通过提高对神经网络连接模式的理解，研发和整个社会作为与相关的大规模连接改变的神经病理学基础特别是，这将改善人类神经精神和神经系统疾病的基础。为复杂的脑部疾病开发新的治疗策略。