Heterogeneity in lobar and near-acini deposition of inhaled aerosol in the mouse lung.

Laboratory animals are often used to derive health risk from environmental exposure or to assess the therapeutic effect of a drug delivered by inhaled therapy. Knowledge of the in-situ distribution of deposited particles on airway and alveolar surfaces is essential in any assessment of these effects. A unique database including both high-resolution lung anatomy and deposition data in four strains of laboratory mice have been recently made publicly available to the research community (https://doi.org/10.25820/9arg-9w56). Using these data, we investigated the effect of particle size on the distribution of deposited particles at the lobar and near-acini level. Analysis was performed on a total of 33 mice where 3, 16 and 14 animals were exposed to 0.5μm, 1μm and 2μm particles, respectively. Ratio of normalized deposition to normalized volume was calculated for each lobe (DV lobe ). At the near-acini level, the skew and standard deviation of the frequency distribution of particle deposition were calculated. Significant deviation above 1 was found for DV ratio in the cranial lobe (DV Cranial ). DV Middle , DV Caudal and DV Accessory were all significantly <1 and lower than DV left (p<0.01). At the near-acini level, skew and standard deviation were positively correlated with particle size and the presence of hot spots (high deposition) were mainly found in the apical region of the lung. These results highlight the uneven distribution of deposited particles in the mouse lung. Thus, depending on the lung sample location, individual analysis to determine overall deposition may either underestimate or overestimate total lung burden, at least for micron-sized particles.