122 LungVis1.0 enables AI-enhanced, high-resolution dosimetry and biokinetics studies in the lung

Abstract Introduction Understanding the dynamic processes of nanoparticle (NP) deposition and subsequent biokinetics in the lung plays a pivotal role in inhalation nanotoxicology and nanomedicine. Here we introduce LungVis1.0, an artificial intelligence (AI) powered imaging ecosystem that enables precise, single-cell resolution mapping of NP distribution and NP-cell interaction in non-dissected lungs. Method NPs (600 nm, melamine) were delivered to murine lungs using four different bulk-liquid and aerosol-based delivery modalities. Whole lung samples were collected at 0 h, 2 h, 1 d, and 14 d post-administration. Tissue clearing and light sheet fluorescence microscopy processed with active/deep learning AI algorithms allowed localization of NPs in precisely segmented, non-dissected airway trees. Complementary data from intravital microscopy, perfused lung models, and flow cytometry is available. Results LungVis1.0 revealed substantial differences in bronchial and acinar NP distribution patterns depending on NP delivery route at macroscopical and microscopical levels. Briefly, bulk-liquid delivery results in patchy NP distribution with elevated bronchial-to-acinar dose ratio (B/A 0.2), whereas aerosol inhalation achieves globally uniform, more alveolar NP deposition with local dose hot-spots in the proximal acinar region. Moreover, lung tissue-resident macrophages (TRMs) exhibited dynamic behaviour, actively patrolling and redistributing NPs within alveoli, challenging the traditional view of TRMs as static cells. Discussion/Conclusions LungVis1.0 provides a comprehensive framework for studying the delivery, biokinetics and cell interaction of NPs in the lung fostering progress in inhalation nanotoxicology/-medicine. The findings underscore the advantages of aerosol delivery for achieving uniform pulmonary NP distribution and the presence of high NP doses in the acinar region, potentially bridging the “sensitivity gap” between in vitro and in vivo models in nanotoxicology.