Multiscale reconstruction of bronchus and cancer cells in human lung adenocarcinoma

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).

Fluorescence micro-optical Sectioning Tomography (fMOST) combined with PI staining were used to obtain the 3D imaging of the human LA tissue at single-cell resolution.

With a spatial resolution of 0.32 × 0.32 × 1.0 μm³, 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 cancer 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 tissue. In paracancerous tissue, 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.

Based on the human LA tissue dataset 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 LA tissue, which may help with the understanding of the main histological structure of LA among pathologists.