Abstract

To investigate the in vivo T1 -enhancement of the lung parenchyma in free-breathing healthy mice following intratracheal administration of Gd-DOTA-based nanoparticles, to assess the enhancement kinetics of the instilled contrast medium and to identify its elimination pathways. Ultrashort Echo Time (276 μs) proton MRI of the lung was performed (N = 14) at 4.7 T after the intratracheal instillation of 50 μL of seven different concentrations of contrast agent solution (from 2 to 100 mM of Gd(3+) ). The signal enhancement (SE) in lungs, blood, liver, kidneys, and bladder was assessed (N = 3) for a 50 mM concentration solution at different time points. The largest SE in lungs (266 ± 14%) was observed for a 50 mM solution of Gd(3+) . In lungs, the SE was observed to decay exponentially with a time constant of 149 ± 51 min. The passage of the nanoparticles from lung tissue to blood and kidneys, and ultimately to the bladder, was observed. No significant hepatic enhancement was measured. This study demonstrates the feasibility of large SEs of lung tissue using intratracheally administrated solutions of Gd-based contrast agents. In future applications, the SE in lungs could be used to image the biodistribution of coadministrated drug aerosols or to selectively enhance lung diseased tissues.

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