MRI-Based Measurements of Aerosol Deposition in the Lung of Healthy and Elastase-Treated Rats
Résumé
Aerosolized drugs are increasingly being used to treat chronic lung diseases or to deliver therapeutics systemically through the lung. The influence of disease, such as emphysema, on particle deposition is not fully understood. Using magnetic resonance imaging (MRI), the deposition pattern of iron oxide particles with mass median aerodynamic diameter (MMAD) of 1.2μm was assessed in the lungs of healthy and elastase-treated rats. Tracheostomized rats were ventilated with particles, at a tidal volume of 2.2ml, and a breathing frequency of 80breaths-min-1. Maximum airway pressure was significantly lower in the elastase-treated (Paw=7.71±1.68 cm H2O) than in the healthy rats (PAW=10.43±1.02 cm H2O, p<0.01). This is consistent with an increase in compliance characteristic of an emphysema-like lung structure. Following exposure, lungs were perfusion-fixed and imaged in a 3T MR scanner. Particle concentration in the different lobes was determined based on a relationship with the MR signal decay rate, R2*. Whole lung particle deposition was significantly higher in the elastase-treated rats (CE,part=3.03±0.61μm/mL) compared to the healthy rats (CH,part=1.84±0.35 μm/mL, p<0.01). However, when particle deposition in each lobe was normalized by total deposition in the lung, there was no difference between the experimental groups. However, the relative dispersion (RD=standard deviation/mean) of R2* was significantly higher in the elastase-treated rats (RDE=0.32±0.02) compared to the healthy rats (RDH=0.25±0.02,p<0.01). These data show that particle deposition is higher and more heterogeneously distributed in emphysematous lungs compared to healthy lungs.