Abstract
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. With the use of magnetic resonance imaging (MRI), the deposition pattern of iron oxide particles with a mass median aerodynamic diameter of 1.2 μm was assessed in the lungs of healthy and elastase-treated rats. Tracheostomized rats were ventilated with particles, at a tidal volume of 2.2 ml, and a breathing frequency of 80 breaths/min. Maximum airway pressure was significantly lower in the elastase-treated (Paw = 7.71 ± 1.68 cmH2O) than in the healthy rats (Paw = 10.43 ± 1.02 cmH2O; 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 ± 0.61 μm/ml) compared with 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 with 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 with healthy lungs.
Highlights
CHRONIC LUNG DISEASES, SUCH AS asthma (21), chronic obstructive pulmonary disease (COPD), and cystic fibrosis (8) are increasingly being treated with aerosolized therapeutics
We have recently developed a magnetic resonance imaging (MRI)-based method, which uses the change in signal decay rate (R2*), due to the presence of iron oxide particles, to quantify the spatial distribution of deposited particles in rodent lungs (13)
LM was larger in the elastase-treated rats than in the healthy rats
Summary
CHRONIC LUNG DISEASES, SUCH AS asthma (21), chronic obstructive pulmonary disease (COPD), and cystic fibrosis (8) are increasingly being treated with aerosolized therapeutics. We have recently developed a magnetic resonance imaging (MRI)-based method, which uses the change in signal decay rate (R2*), due to the presence of iron oxide particles, to quantify the spatial distribution of deposited particles in rodent lungs (13). Our previous study used healthy rats to demonstrate the feasibility of using MRI to detect and quantify regional aerosol particle deposition in rodent lungs. This method can be readily applied to a variety of animal models of human disease. This study is the first to determine changes in deposition between healthy and elastase-treated rat lungs exposed to aerosolized particles with similar breathing patterns and may be used to validate numerical simulations of particle transport in the rat lung (11)
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