Laryngeal birth defects are considered rare, but they can be life-threatening conditions. The BMP4 gene plays an important role in organ development and tissue remodeling throughout life. Here we examined its role in laryngeal development complementing similar efforts for the lung, pharynx, and cranial base. Our goal was to determine how different imaging techniques contribute to a better understanding of the embryonic anatomy of the normal and diseased larynx in small specimens. Contrast-enhanced micro CT images of embryonic larynx tissue from a mouse model with Bmp4 deletion informed by histology and whole-mount immunofluorescence were used to reconstruct the laryngeal cartilaginous framework in three dimensions. Laryngeal defects included laryngeal cleft, laryngeal asymmetry, ankylosis and atresia. Results implicate BMP4 in laryngeal development and show that the 3D reconstruction of laryngeal elements provides a powerful approach to visualize laryngeal defects and thereby overcoming shortcomings of 2D histological sectioning and whole mount immunofluorescence.

Effective evaluation and prediction of aerosol transport deposition in the human respiratory tracts are critical to aerosol drug delivery and evaluation of inhalation products. Establishment of an in vitro-in vivo correlation (IVIVC) requires the understanding of flow and aerosol behaviour and underlying mechanisms at the microscopic scale. The achievement of the aim can be facilitated via computational fluid dynamics (CFD) based in silico modelling which treats the aerosol delivery as a two-phase flow. CFD modelling research, in particular coupling with discrete phase model (DPM) and discrete element method (DEM) approaches, has been rapidly developed in the past two decades. This paper reviews the recent development in this area. The paper covers the following aspects: geometric models of the respiratory tract, CFD turbulence models for gas phase and its coupling with DPM/DEM for aerosols, and CFD investigation of the effects of key factors associated with geometric variations, flow and powder characteristics. The review showed that in silico study based on CFD models can effectively evaluate and predict aerosol deposition pattern in human respiratory tracts. The review concludes with recommendations on future research to improve in silico prediction to achieve better IVIVC.

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.