Multiscale reconstruction of bronchus and cancer cells in human stage II lung adenocarcinoma 

Background: While previous studies primarily focused on the structure of the normal whole mouse lung, the whole bronchus and cytoarchitectural details of the mouse intact lung lobe have been discovered at single-cell resolution. Revealing the sophisticated lung adenocarcinoma structure at three-dimensional (3D) and single-cell level remains a fundamental and critical challenge for the pathological mechanism research of lung adenocarcinoma (LA). Methods Fluorescence micro-optical Sectioning Tomography (fMOST) combined with PI staining were used to obtain the 3D imaging of the human LA tissues at single-cell resolution. Results With a spatial resolution of 0.32 × 0.32 × 1.0 µm 3 , the dataset of human LA with single-cell precision consists of two channels, each of which contains information about the bronchi and the cytoarchitecture. The bronchial wall is thicker and the lumen is smaller in the adenocarcinoma tissue, in which its original normal structure is vanished. More solid components, more clustered cancer cells with larger nucleoli, and more significant atypia are found in cancer tissues. In paracancerous tissues, the bronchial wall cells have a monolayer or bilayer structure, cluster along the wall, and are relatively dispersed. Few fibrous structures and occasional dissemination of spread through air spaces (STAS) are observed. Conclusions Based on the human lung adenocarcinoma tissue database obtained by fMOST and PI staining, the bronchi and cells were reconstructed and visualized. This work provides a technical roadmap for studying the bronchus and cytoarchitectural structure and their spatial relationship in lung adenocarcinoma tissue, which will help with the accurate diagnosis and assessment of the medical effectiveness of lung adenocarcinoma in the future.