Abstract The development of predictive aerosol dosimetry models has been a major focus of environmental toxicology and pharmaceutical health research for decades. One-dimensional (1D) models successfully predict overall deposition averages but fail to accurately predict local deposition. Computational fluid-particle dynamics (CFPD) models provide site-specific predictions but at a computational cost that prohibits whole lung predictions. Thus, there is a need for developing multiscale strategies to provide a realistic subject-specific picture of the fate of inhaled aerosol in the lungs. CT-based 3D/CFPD models of the large airways were bidirectionally coupled with individualized 1D Navier-Stokes airflow and particle transport based upon the widely used Multiple Path Particle Dosimetry Model (MPPD). Distribution of airflows among lobes was adjusted by measured lobar volume changes observed in CT images between FRC and FRC +1.5 L. As a test of the effectiveness of the coupling procedures, deposition modeling of previous 1 μm aerosol exposure studies was performed. The complete coupled model was run for 3 breaths, with the computation-intense portion being the 3D CFPD Lagrangian particle tracking calculation. The average deposition per breath was 11% in the combined multiscale model with site-specific doses available in the CFPD portion of the model and airway- or region-specific deposition available for the MPPD portion. In conclusion, the key methods developed in this study enable predictions of ventilation heterogeneities and aerosol deposition across the lungs that are not captured by 3D or 1D models alone. These methods can be used as the foundation for multi-scale modeling of the full respiratory system.

中文翻译：

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3D 计算流体-粒子动力学和 1D 多路径粒子剂量学肺模型的高效双向耦合，用于气溶胶剂量学的多尺度建模

摘要 几十年来，预测气溶胶剂量学模型的开发一直是环境毒理学和药物健康研究的主要焦点。一维 (1D) 模型成功预测了总体沉积平均值，但无法准确预测局部沉积。计算流体粒子动力学 (CFPD) 模型提供特定于站点的预测，但计算成本禁止整个肺预测。因此，需要开发多尺度策略来提供肺部吸入气溶胶归宿的真实主题特定图片。大气道的基于 CT 的 3D/CFPD 模型与基于广泛使用的多路径粒子剂量学模型 (MPPD) 的个性化 1D Navier-Stokes 气流和粒子传输双向耦合。通过在 FRC 和 FRC +1.5 L 之间的 CT 图像中观察到的测量的肺叶体积变化来调整叶之间的气流分布。为了测试耦合程序的有效性，对先前的 1 μm 气溶胶暴露研究进行了沉积建模。完整的耦合模型运行 3 次呼吸，计算密集部分是 3D CFPD 拉格朗日粒子跟踪计算。在组合多尺度模型中，每次呼吸的平均沉积为 11%，模型的 CFPD 部分提供特定部位的剂量，MPPD 部分提供气道或区域特定的沉积。总之，本研究中开发的关键方法能够预测仅 3D 或 1D 模型无法捕获的通气异质性和肺部气溶胶沉积。