MRI Measurement of Regional Lung Deposition in Mice Exposed Nose-Only to Nebulized Superparamagnetic Iron Oxide Nanoparticles

Abstract

Superparamagnetic iron oxide nanoparticles show potential in magnetic targeting of inhaled aerosols to localized sites within the lung. These particles are also used as contrast agents in magnetic resonance imaging (MRI). In the present work, we examine the feasibility of measuring regional lung deposition of iron oxide nanoparticles using MRI. Mice were exposed nose-only to nebulized superparamagnetic iron oxide nanoparticles. The droplet size distribution in the inhalation chamber was measured using a time-of-flight device. Regional concentrations of iron in the left and right lung were assessed with MRI by measuring the longitudinal relaxation times (T₁) of the lung tissue in exposed mice, compared to a baseline group. Regional concentrations of iron in the lungs of the mice ranged from 1.1 ± 0.8 μg/cm³ (mean ± one standard deviation, n = 6) in peripheral lung regions to 2.7 ± 1.4 μg/cm³ in the central lung, with no significant difference between the left and right lung. The nebulized droplets in the inhalation chamber had mass median aerodynamic diameter (MMAD) of 5.6 ± 0.8 μm, with a geometric standard deviation (GSD) of 1.30 ± 0.03 (both values expressed as mean ± one standard deviation, n = 6). MRI shows promise for in vivo measurement of regional lung concentrations of superparamagnetic iron oxide nanoparticles, and may be useful in studies of lung deposition and clearance.