Abstract Rationale Inhaled particles carrying pathogens, pollutants (e.g., microplastics, smoke), therapeutics, and diagnostics are increasingly relevant to public health. However, real-time transport of aerosols in functional alveoli is poorly understood as clinical imaging methods (CT, MRI) lack sufficient spatiotemporal resolution for probing alveoli, and histology provides only static endpoints. Subsequently, factors governing aerosol deposition dynamics in alveoli have remained unexplored. We developed a transparent “crystal” ribcage that enables optical access to intact, ventilated lungs, allowing real-time visualization of single aerosol droplets during physiological breathing. Using this platform, we observed the formation of a deterministic, heterogeneous “mosaic pattern” of aerosol distribution, in which only specific alveolar clusters received particles. Methods Fluorescent aerosols (1-10 µm) were delivered under spontaneous breathing in vivo or during ex vivo mechanical ventilation in mouse lungs. We utilized the crystal ribcage (Banerji Beckman Young Investigator Award; NSF CAREER Award; Hevolution/AFAR New Investigator Award
Grifno et al. (Fri,) studied this question.