The Development of Tabletop Brain-Mapping Platform

项目摘要 中枢神经系统（CNS）疾病给社会带来巨大负担， 是开发治疗方法最具挑战性的领域。的一大原因 大脑是一个复杂的、三维的、多尺度的器官， 在数百个大脑区域中的组成部分。广泛的BRAIN倡议正在进行中 通过对连接模式和小区类型进行调查来绘制这种复杂性。数字 诸如艾伦小鼠脑CCF v3.0之类的脑图谱已经成为组织 这些努力的结果。 艾伦CCFV3.0和全脑调查的可用性正在改变CNS研究。 然而，大脑映射仍然太频繁地需要使用昂贵的设备， 技术和敬业的员工。此外，许多新技术与 已建立的组织学方案，这严重限制了基础研究的贡献。 技术到大脑绘图的努力。此外，繁琐的手工制作幻灯片 仍然是高通量组织学的显著障碍。这些困难提出了一个 这是该领域的重大障碍，并阻碍了对CNS的理解。 该提案将通过开发负担得起的桌面硬件来消除这些障碍， 非专业人员可访问的软件小鼠脑成像和组织处理平台 神经科学实验室它是基于成熟的切片，部分捕获，和幻灯片安装 TissueVision的商业上成功的最先进的多光子技术中包含的技术， 基于TissueCyte平台。这项建议将扩大我们现有系统的能力， 将其扩展到薄至15微米的切片并取代TissueCyte的先进多光子 用较便宜的块面成像进行成像。在第二阶段，我们将把综合 将组织处理技术转化为方便、紧凑的仪器。这款桌面，价格实惠 该设备将联合收割机结合了2D切片和3D大脑分析的功能 并帮助推动新疗法的发展。 该产品将由TissueVision的世界级专家团队推向市场， 在高通量组织学仪器方面有成功的商业化经验 和大脑图谱我们将得到一流神经科学领域合作伙伴的帮助 实验室将对产品进行beta测试，并在第二阶段提供关键反馈，以确保 成功的产品投放市场并被市场接受。

PROJECT SUMMARY Central Nervous System (CNS) disorders place an enormous burden on society and have proven to be among the most challenging areas for which to develop a therapeutic. A major reason for this is that the brain is a complex, 3D, multiscale organ, with a heterogenous distribution of components across hundreds of brain regions. Extensive BRAIN Initiative efforts are underway to map this complexity by conducting surveys of connectivity pattern and cells types. Digital brain atlases such as the Allen Mouse Brain CCF v3.0 have become essential tools in organizing the results of these endeavors. The availability of the Allen CCFV3.0 and whole-brain surveys are transforming CNS studies. However, brain mapping still too frequently requires access to expensive equipment, specialized techniques, and dedicated personnel. Moreover, many newer techniques are incompatible with established histology protocols, which severely limits the contribution of foundational techniques to brain mapping efforts. In addition, the tedious manual production of slides remains a significant obstacle to high throughput histology. These difficulties present a significant barrier to the field and hinders progress in understanding the CNS. This proposal will remove these barriers by developing an affordable, table-top hardware and software mouse brain imaging and tissue processing platform accessible to the non-specialist neuroscience lab. It is based on the proven microtomy, section capture, and slide mounting technology contained in TissueVision's commercially successfully state-of-the-art multiphoton- based TissueCyte platform. This proposal will extend the capabilities of our current system and extend it to sections as thin as 15 microns and replace the TissueCyte's advanced multiphoton imaging with less expensive block-face imaging. In Phase II we will be package the integrated tissue processing technology into a convenient, compact instrument. This table-top, affordable device will combine the ease of working from 2D sections with the power of 3D brain analyses and help propel forward the development of new therapeutics. This product will be brought to market by a team of world-class experts at TissueVision who have successful commercialization experience in instrumentation for high throughput histology and brain mapping. We will be aided by a superb network of partners in leading neuroscience labs who will beta test the product and provide crucial feedback in Phase II to ensure a successful product launch and acceptance into the marketplace.