Histological examinations typically require the excision of tissue, followed by its fixation, slicing, staining, mounting and imaging, with timeframes ranging from minutes to days. This process may remove functional tissue, may miss abnormalities through under-sampling, prevents rapid decision-making, and increases costs. Here, we report the feasibility of microscopes based on swept confocally aligned planar excitation technology for the volumetric histological imaging of intact living tissue in real time. The systems’ single-objective, light-sheet geometry and 3D imaging speeds enable roving image acquisition, which combined with 3D stitching permits the contiguous analysis of large tissue areas, as well as the dynamic assessment of tissue perfusion and function. Implemented in benchtop and miniaturized form factors, the microscopes also have high sensitivity, even for weak intrinsic fluorescence, allowing for the label-free imaging of diagnostically relevant histoarchitectural structures, as we show for pancreatic disease in living mice, for chronic kidney disease in fresh human kidney tissues, and for oral mucosa in a healthy volunteer. Miniaturized high-speed light-sheet microscopes for in-situ volumetric histological imaging may facilitate the point-of-care detection of diverse cellular-level biomarkers.

组织学检查通常需要切除组织，然后进行固定、切片、染色、封固和成像，时间从几分钟到几天不等。此过程可能会去除功能组织，可能会因采样不足而错过异常情况，妨碍快速决策并增加成本。在这里，我们报告了基于扫描共焦对齐平面激发技术的显微镜对完整活体组织进行实时体积组织学成像的可行性。该系统的单目标、光片几何结构和 3D 成像速度可实现移动图像采集，与 3D 拼接相结合，可以对大组织区域进行连续分析，并对组织灌注和功能进行动态评估。这些显微镜以台式和小型化的形式实现，即使对于微弱的固有荧光也具有高灵敏度，允许对诊断相关的组织结构结构进行无标记成像，正如我们对活体小鼠的胰腺疾病、新鲜小鼠的慢性肾病所展示的那样。人类肾组织，以及健康志愿者的口腔粘膜。用于原位体积组织学成像的小型化高速光片显微镜可能有助于多种细胞水平生物标志物的即时检测。