Evaluation of nasal spray drug absorption has been challenging because deposited particles are consistently transported away by mucociliary clearance during diffusing through the mucus layer. This study developed a novel approach combining Computational Fluid Dynamics (CFD) techniques with a 1-D mucus diffusion model to better predict nasal spray drug absorption. This integrated CFD-diffusion approach comprised a preliminary simulation of nasal airflow, spray particle injection, followed by analysis of mucociliary clearance and drug solute diffusion through the mucus layer. The spray particle deposition distribution was validated experimentally and numerically, and the mucus velocity field was validated by comparing with previous studies. Total and regional drug absorption for solute radius in the range of 1 − 110nm were investigated. The total drug absorption contributed by the spray particle deposition was calculated. The absorption contribution from particles that deposited on the anterior region was found to increase significantly as the solute radius became larger (diffusion became slower). This was because the particles were consistently moved out of the anterior region, and the delayed absorption ensured more solute to be absorbed by the posterior regions covered with respiratory epithelium. Future improvements in the spray drug absorption model were discussed. The results of this study are aimed at working towards a CFD-based integrated model for evaluating nasal spray bioequivalence.

The scarcity of regional deposition data in distal respiratory airways represents an important challenge for current toxicology and pharmacology research. To bridge this gap, a realistic airway model extending from nasal and oral openings to distal bronchial airways with varying pathway length was built in this study. Transport and deposition characteristics of naturally inhaled ultrafine particles (UFPs) ranging from 1 to 100 nm were numerically investigated, and effects of different inhalation scenarios were considered. To enable intercase particle deposition comparison, an adjusted parameter, unified deposition enhancement factor (UDEF), was proposed for quantifying the localised deposition concentration. Results show that compartment particle deposition peaked around the ultrafine end of the considered size range, and it dropped rapidly with the increase of particle size. Different inhalation modes caused notable deposition changes in the extrathoracic region, while its effects in the TB airway are much less. For UFPs larger than 10 nm, predicted deposition efficiencies in all compartments are all at lowest levels among considered particle size range, implying UFPs ranging from 10 to 100 nm can travel through the whole respiratory airway model and escape to the alveolar region. Furthermore, high enhancement factors were observed at the vicinity of most bifurcation apexes, and more even UDEF distribution was observed from 1‐nm particle cases. While for 100‐nm cases, the deposited particles tend to concentrate at few “hot spots” (areas of high deposition concentration in relation to surrounding surfaces) with greater UDEF in the tracheobronchial airway.

PurposeThe aim of this study was to quantify the displacement of cardiac substructures, including the anterior myocardial territory (AMT), left ventricle, and coronary arteries during a normal cardiac cycle.Materials and methodsComputed tomography (CT) images with retrospective electrocardiographic gating of 17 eligible patients were obtained. All images were reconstructed automatically for the end-diastolic and end-systolic phases. CT scanning without contrast at a random phase and a selected vertebral body were used as references to measure three-dimensionaldisplacements of the cardiac substructures.ResultsThe displacement between the end-diastolic and end-systolic phases (Dd-s) was greater than that between the end-systolic and random phases and between the end-diastolic and random cardiac phases. The largest displacements for the heart were in the left, posterior, and inferior directions with an average Dd-s of approximately 4–6 mm. The average Dd-s for the AMT and left ventricle was 1.2–2.7 mm in the anterior and right directions, 4.3–7.8 mm in left and posterior directions, and 4.9–6.3 mm in superior and inferior directions. For the coronary arteries, the average Dd-s was 2.8–5.9 mm in the anterior-posterior direction, 3.5–6.6 mm in left-right direction, and 3.8–5.3 mm in the superior-inferior direction. Inter-observer agreement was excellent for the heart, AMT, and left ventricle (kappa coefficient, >0.75 for all) and good for most coronary arteries in three dimensions (kappa coefficient, 0.511–0.687). The Dd-s did not differ significantly between men and women.ConclusionMost average displacements of the cardiac substructures and coronary arteries were 3–8 mm in three dimensions. These findings will be useful to accurately estimate the radiation dose to cardiac substructures during thoracic radiation and to evaluate the risk of radiation-related heart disease.

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