Abstract
The toxic or therapeutic effect of an inhaled aerosol is highly dependent upon the site and extent of deposition in the lung. A novel MRI-based method was used to quantify the spatial distribution of particles in the rat lung. Rats were exposed to 0.95 μm-diameter iron oxide particles in a controlled manner (N = 6) or to particle-free air (N = 6). Lungs were fixed in 3% glutaraldehyde by vascular perfusion, excised and imaged in a 3T scanner using a gradient-echo imaging protocol. The signal decay rate, R2*, was measured in each voxel of the entire left lung (1 mm thick slices). R2* was significantly higher in exposed animals (0.0065 ± 0.0006 ms(-1)) than in controls (0.0050 ± 0.0003 ms(-1), p < 0.001). A calibration curve between R2* and concentration of deposited particles (C(part)) was obtained by imaging gel samples with known particle concentrations. Regional deposition was assessed by comparing C(part) between the outer (C(part,peripheral)) and inner (C(part,central)) areas on each transaxial slice, and expressed as the c/p ratio. C(part,peripheral) (1.54 ± 0.70 μg/mL) was significantly higher than C(part,central) (1.00 ± 0.39 μg/mL, p<0.05), resulting in a c/p ratio of 0.65. This method may be used in future studies to quantify spatial distribution of deposited particles in healthy and diseased lungs.