The Development of Tabletop Brain-Mapping Platform

项目总结 中枢神经系统(CNS)疾病给社会带来了巨大的负担，并已被证明 成为最具挑战性的领域之一，为其制定治疗方案。一个主要原因是 这就是说，大脑是一个复杂的、3D的、多尺度的器官，具有不同分布的 数百个大脑区域的组件。广泛的大脑倡议工作正在进行中 通过对连接模式和细胞类型进行调查来描绘这种复杂性。数位 像Allen Mouse Brain CCF v3.0这样的脑图集已经成为组织 这些努力的结果。 Allen CCFV3.0和全脑调查的出现正在改变中枢神经系统的研究。 然而，脑成像仍然经常需要使用昂贵的设备，专门的 技术和敬业的人员。此外，许多较新的技术与 建立了组织学方案，这严重限制了基金会的贡献 从技术到脑成像的努力。此外，繁琐的幻灯片手工制作 仍然是高通量组织学的一个重大障碍。这些困难提出了一个 这是该领域的重大障碍，阻碍了对中枢神经系统的了解取得进展。 这项提议将通过开发负担得起的桌面硬件和 非专业人员可访问的软件鼠脑成像和组织处理平台 神经科学实验室。它的基础是成熟的显微切割、切片捕获和滑动安装 TIseVision商业上成功的最先进的多光子技术-- 基于TisseCyte平台。这项建议将扩展我们现有系统的能力，并 将其扩展到薄至15微米的部分，取代TisseCyte先进的多光子 使用价格较低的块面成像。在第二阶段，我们将打包集成的 将组织处理技术转化为一种方便、紧凑的仪器。这个桌面，价格实惠 该设备将结合从2D切片进行操作的简便性和3D大脑分析的功能 并有助于推动新疗法的发展。 该产品将由TIseVision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 和脑电图仪。我们将得到领先神经科学合作伙伴的卓越网络的帮助 将对产品进行Beta测试并在第二阶段提供重要反馈的实验室，以确保 成功地将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.