Understanding cellular architectures and their connectivity is essential for interrogating system function and dysfunction. However, we lack technologies for mapping the multiscale details of individual cells and their connectivity in the human organ–scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, and connectivity information of individual cells from the same human brain. The platform includes three core elements: a vibrating microtome for ultraprecision slicing of large-scale tissues without losing cellular connectivity (MEGAtome), a polymer hydrogel–based tissue processing technology for multiplexed multiscale imaging of human organ–scale tissues (mELAST), and a computational pipeline for reconstructing three-dimensional connectivity across multiple brain slabs (UNSLICE). We applied this platform for analyzing human Alzheimer’s disease pathology at multiple scales and demonstrating scalable neural connectivity mapping in the human brain.

中文翻译：

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人脑多尺度分子成像和表型分析集成平台


了解细胞结构及其连接对于询问系统功能和功能障碍至关重要。然而，我们缺乏绘制人体器官尺度系统中单个细胞的多尺度细节及其连接性的技术。我们开发了一个平台，可以同时提取同一人脑中单个细胞的空间、分子、形态和连接信息。该平台包括三个核心要素：用于在不丢失细胞连接的情况下对大型组织进行超精密切片的振动切片机（MEGAtome）、用于人体器官规模组织多重多尺度成像的基于聚合物水凝胶的组织处理技术（mELAST）和用于重建跨多个脑板的三维连接的计算管道（UNSLICE）。我们应用该平台在多个尺度上分析人类阿尔茨海默病病理学，并展示人脑中可扩展的神经连接映射。