In Vivo Performance of Airway and Lung Ultrasound Enhanced via Inhalable Contrast Agents

Abstract

Tracheal and distal airway imaging enhance the evaluation of mucociliary clearance (MCC) and respiratory health. Herein, we characterize in vivo pulmonary imaging performance of a microbubble (MB) contrast agent optimized for muco-adhesion. A three-way crossover trial (12 mice, 3 imaging timepoints each) was conducted to evaluate tracheal ultrasound image enhancement following oropharyngeal instillation of standard MBs, our optimized MB formulation (TAP-cationic MBs), and lipid solution control. The feasibility of delivering our TAP-cationic MBs as an aerosol to the distal airways was also evaluated using a porcine model. Contrast imaging procedures were well-tolerated by both animal models. In mice, tracheal delineation was comparably enhanced with TAP-cationic MBs (contrast-to-noise ratio [CNR]: 42.26 dB) and standard MBs (CNR: 45.09 dB). Both exceeded lipid solution control (CNR: 11.9 dB, p < .05). In the porcine model, nebulized administration of TAP-cationic MBs yielded MB accumulation in the distal airways visible on transcutaneous ultrasound. Modifying the standard MB formulation to optimize muco-adhesion does not diminish image enhancement when administered oropharyngeally as a liquid solution, and when administered as an aerosol, TAP-cationic MBs deposit, and can be visualized in the distal lung airways. These findings support further development of MB contrast agents for pulmonary applications.