The impact of pathological ventilation on aerosol deposition : imaging, insight and intervention

Abstract

Aerosol therapies are often used to treat lung diseases in which ventilation is distributed heterogeneously throughout the lung. As therapeutic aerosols are transported by the inhaled air, it is likely that deposition is diminished within poorly ventilated regions of the lung. These regions are often the most in need of therapy. We measured the effects of heterogeneous ventilation on aerosol deposition in a group of bronchoconstricted asthmatic subjects. We then developed a new image processing technique which allowed us to identify the anatomical location of aerosol deposition. This technique accounted for blurring due to limited resolution of the PET image, motion artifacts due to breathing, and registration uncertainty. We introduced a theoretical framework to characterize four mechanisms of variability in deposition between peripheral regions of the lung. This framework added insight into the interaction between ventilation and deposition, and will permit the future comparison of the experimental data with computational models. Together, the imaging data and theoretical framework suggested that more than a third of the observed variability in the deposition per unit volume among lung lobes was due to heterogeneous ventilation. Using helium-oxygen as a carrier gas for aerosol has been considered as a potential intervention to homogenize deposition in the lung periphery. To investigate this, we repeated the PET-CT measurements in a second group of bronchoconstricted asthmatic subjects breathing helium-oxygen, and compared the results to those of the group breathing room air. We did not find systematic differences in the deposition patterns of the two groups, although the relationship between ventilation and aerosol deposition tended to be stronger in the group that used helium-oxygen as the carrier gas. Finally, we used analytical tools and an in-silico model of bronchoconstriction to illustrate the emergence of pendelluft gas transport between parallel regions of the lung. We found that though pendelluft may emerge in asthma, the overall volume passed between parallel regions of the lung is likely less than 2% of the tidal volume, and thus is not likely to substantially influence aerosol deposition.