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.

中文翻译：

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小鼠肺中吸入气溶胶的大叶和近腺泡沉积的异质性

实验动物通常用于从环境暴露中得出健康风险或评估通过吸入疗法递送的药物的治疗效果。了解沉积颗粒在气道和肺泡表面的原位分布对于评估这些影响至关重要。一个独特的数据库包括四种实验室小鼠的高分辨率肺解剖和沉积数据，最近已向研究界公开 (https://doi.org/10.25820/9arg-9w56)。使用这些数据，我们研究了粒径对大叶和近腺泡水平沉积颗粒分布的影响。对总共 33 只小鼠进行了分析，其中 3、16 和 14 只动物分别暴露于 0.5μm、1μm 和 2μm 颗粒。计算每个叶 (DV 叶) 的归一化沉积与归一化体积的比率。在近腺泡水平，计算了粒子沉积频率分布的偏斜和标准偏差。在颅叶 (DV Cranial) 中发现 DV 比值高于 1 的显着偏差。DV Middle 、DV Caudal 和 DV Accessory 均显着 <1 且低于 DV left (p<0.01)。在近腺泡水平，偏斜和标准偏差与粒径呈正相关，热点（高沉积）的存在主要存在于肺尖区域。这些结果突出了小鼠肺中沉积颗粒的不均匀分布。因此，根据肺样本位置，确定总体沉积的个体分析可能低估或高估总肺负荷，