Creating a Novel Museum-Based Resource for Neuroscience: Mass whole-slide imaging of the R. Glenn Northcutt Collection of Comparative Vertebrate Neuroanatomy and Embryology

该项目将使在线访问一个独特的，不可替代的资源，比较研究的进化和发展的脊椎动物大脑。中华民国Glenn Northcutt比较脊椎动物神经解剖学和胚胎学收藏，位于哈佛比较动物学博物馆（MCZ），是世界上最大的和分类学上最多样化的发育和成年脊椎动物大脑组织学标本的收藏。这是特别感兴趣的和相关的神经科学家使用分子和遗传方法来阐明进化创新的机制，但幻灯片是脆弱的，访问它们是困难和耗时的。通过利用与哈佛脑科学中心合作开发的全载玻片成像工作流程，该项目将使专业科学家、教育工作者和学生能够通过高分辨率数字图像轻松、常规地访问载玻片内容。这种访问将有助于在研究和教育中使用幻灯片，并补充研究大脑结构，发育和功能的新技术。它将促进神经科学和生物多样性社区之间的合作，并与其他寻求大规模数字化和共享生物收藏品的项目一起，它将提高自然历史机构的能力，使其能够更充分地为科学和社会服务，超越其传统选区。事实上，该项目的成像工作流程和相关的培训组件提供了一种快速和具有成本效益的数字化示范方法，可供其他机构使用，这些机构的幻灯片数量数以百万计，其中大部分仍然是暗数据。该项目将使用高通量，半自动幻灯片扫描仪制作约33，000个显微镜载玻片在Northcutt Collection。该项目完成后，将提供在线访问约500，000个连续切片和240多个属和270个物种的活脊椎动物的成年大脑和胚胎的整体标本。将利用具有成本效益的全载玻片成像工作流程，每周处理多达360张载玻片，同时产生出色的图像分辨率（在40倍和20倍放大倍率下分别为0.2和0.4 μm/像素）。每张幻灯片的数字图像将通过两个在线门户网站提供给潜在用户：MCZbase，比较动物学博物馆的永久标本数据库;和MorphoSource，NSF支持的标本数字图像在线存储库。这两个门户网站将配置有Girder和SlideAtlas，这两个开源软件工具用于查看、下载和分析整个幻灯片图像。此外，对于多达20个被广泛用于教授比较脊椎动物解剖学的物种，标记为指出主要大脑区域的组织切片子集的数字图像将被上传到BrainMaps，这是一个脊椎动物神经解剖学的在线资源。最后，该项目将产生几个资源，用于培训学生和专业人员的方法，大规模数字化和计算机辅助可视化的幻灯片集合，无论主题。这些资源包括四个“如何”视频，两个在线教程，本科生和研究生实习以及博物馆研究的研究生课程。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project will enable online access to a unique, irreplaceable resource for comparative studies of the evolution and development of the vertebrate brain. The R. Glenn Northcutt Collection of Comparative Vertebrate Neuroanatomy and Embryology, housed in Harvard’s Museum of Comparative Zoology (MCZ), is the world’s largest and most taxonomically diverse collection of histological preparations of developing and adult vertebrate brains mounted on glass microscope slides. It is of particular interest and relevance to the current generation of neuroscientists who use molecular and genetic approaches to elucidate mechanisms underlying evolutionary innovations, but the slides are fragile and access to them is difficult and time consuming. By utilizing a whole-slide-imaging workflow developed through a novel collaboration with Harvard’s Center for Brain Science, the project will allow professional scientists, educators and students to easily and routinely access the slides’ content via high-resolution digital images. Such access will facilitate use of the slides in research and education and complement novel technologies for studying brain structure, development and function. It will facilitate collaborations between the neuroscience and biodiversity communities and, together with other projects that seek mass digitization and sharing of biological collections, it will enhance the ability of natural history institutions to more fully serve both science and society beyond their traditional constituencies. Indeed, the project’s imaging workflow and associated training components offer an exemplar method for rapid and cost-effective digitization that can be used by other institutions, whose slide holdings number in the millions, most of which remain dark data.The project will use a high-throughput, semi-automated slide scanner to make high-resolution digital images of the approximately 33,000 glass microscope slides in the Northcutt Collection. When completed, the project will provide online access to approximately 500,000 serial sections and whole-mount preparations of adult brains and embryos of more than 240 genera and 270 species of living vertebrates. A cost-effective whole-slide imaging workflow will be utilized to process as many as 360 slides/week while yielding excellent image resolution (0.2 and 0.4 μm/pixel at 40X and 20X magnification, respectively). A digital image of each slide will be served to potential users via two online portals: MCZbase, the Museum of Comparative Zoology’s permanent specimen database; and MorphoSource, an NSF-supported online repository for specimen digital imagery. Both portals will be configured with Girder and SlideAtlas, two open-source software tools for whole-slide image viewing, downloading and analysis. In addition, for as many as 20 species widely used to teach comparative vertebrate anatomy, digital images of a subset of histological sections labelled to point out principal brain regions will be uploaded to BrainMaps, an online resource for vertebrate neuroanatomy. Finally, the project will produce several resources for training both students and professionals in methods for mass digitization and computer-assisted visualization of slide collections regardless of subject matter. These resources include four “how-to” videos, two online tutorials, undergraduate and graduate student internships and a graduate-level course in museum studies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.