ClearScope

清晰范围

• 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
• 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

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.

在体内和离体三维（3D）非转基因的全脑成像和 转基因动物模型具有对神经网络连通性模式的新见解的希望。 关于3D全脑数据集的体内光显微显微镜成像，最好的方法是大脑 清除，然后是全脑光片显微镜（LSM），因为它的独特组合 与共聚焦和多光子显微镜相比，速度，3D分辨能力以及低光毒性。 与其他方法不同，大脑清除 / LSM方法可以使用完整的组织 并保留大脑结构内所有细胞内连接。但是，LSM系统在商业上 可用的不适合3D全脑数据集中的体内光显微镜成像 连接组学研究。最近，Raju Tomer博士（纽约州纽约州哥伦比亚大学的Biol。Sci。 开发的轻片theta显微镜（LSTM），本质上是两个轻纸的独特布置 斜与试样的倾斜和一个垂直于样品的检测目标。这本小说 显微镜是LSTM中多种功能的基础，这些功能并非所有其他功能 市售的LSM系统。 LSTM技术在共凝块和 其他轻板显微镜，包括无与伦比的图像厚度组织标本的能力 在更高的光学分辨率下，较大的横向面积（XY），同时保持快速成像速度，高成像 质量和低摄影。这项有希望的技术是该实验室的基础 开发ClearScope™的市场建议，该提议完善并改善了Tomer博士的原始 LSTM系统创建成功采用广泛采用的商业显微镜。关键技术 将ClearScope作为商业产品开发的目标包括创建和测试（i） 基于优化显微镜硬件设计的ClearScope原型； （ii）新型显微镜 ClearScope的硬件组件，完成一个包含已研究的新型室 标本和浸入培养基，以及一种新颖的检测目标改变者； （iii）新颖的控制和 ClearScope的图像采集软件；重要的是，（iv）超过该软件 现有的最新技术将获得的获得图像堆组成大型3D图像量 超过10TB而无需对图像信息进行下样本。生产版本的 ClearScope将受益于神经科学研究社区，药物和生物技术 研发，以及一般的社会，通过提高对神经网络连接模式的理解 作为与 人类神经精神病和神经系统状况。特别是，这将改善 用于制定复杂脑部疾病的新型治疗策略。