Aerosol deposition in the lungs of spontaneously breathing rats using Gd-DOTA-based contrast agents and ultra-short echo time MRI at 1.5 Tesla.

Abstract

Aerosol toxicology and drug delivery through the lungs, which depend on various parameters, require methods to quantify particle deposition. Intrapulmonary-administered MRI contrast agent combined with lung-specific imaging sequences has been proposed as a high performance technique for aerosol research. Here, aerosol deposition is assessed using ultra-short echo (UTE) sequences. Before and after administration of Gd-DOTA-based aerosol delivered nose-only in free-breathing healthy rats, a T1 -weighted 3D UTE sequence was applied in a clinical 1.5 Tesla scanner. Administration lasted 14 min, and the experiment was performed on six rats. A contrast-enhanced quantitative analysis was done. Fifty percent signal enhancement was obtained in the lung parenchyma. Lung clearance of the contrast agent was evaluated to be 14% per h (corresponding to a characteristic clearance time of 3.6 h) and aerosol deposition was shown to be homogeneous throughout the lung in healthy rats. The total deposited dose was estimated to be 1.05 µmol/kg body weight, and the concentration precision was 0.02 mM. The UTE protocol with nebulized Gd-DOTA is replicable to significantly enhance the lung parenchyma and to map aerosol deposition. This functional strategy, applied in a clinical system with a clinical nebulization setup and a low inhaled dose, suggests a feasible translation to human.