Perfluorocarbon compound aerosols for delivery to the lung as potential 19F magnetic resonance reporters of regional pulmonary pO2

Abstract

Rationale and objectives: Perfluorocarbon (PFC) aerosols present the opportunity for simultaneous analysis of lung structure and pulmonary oxygenation patterns. The authors investigated techniques to nebulize neat liquid PFCs for inhalation as a new method of PFC administration and tested the hypothesis that PFC aerosols may be developed for efficient delivery to the lung in an experimental rat model allowing the potential for sequential monitoring of pulmonary status via quantitative fluorine-19 (19F) magnetic resonance (MR) partial pressure of oxygen (pO2) imaging.

Methods: Pneumatic aerosol generators were configured to produce a neat liquid PFC perfluorotributylamine (FC-43) aerosol. Perfluorocarbon inhalation breathing protocols for the rat model included: spontaneous direct breathing from an aerosol chamber, and use of a tracheotomy tube to bypass nasal breathing. The PFC aerosol delivery into the rat lung was documented through 19F MR imaging in correlation with high-resolution anatomic proton MR images. Theoretical model calculations for PFC mass deposition were compared with experimental results.

Results: The pneumatic generator produced a PFC aerosol droplet within the theoretically targeted range (geometric mean particle diameter of 1.2 microns; concentration of approximately 4 x 10(7) droplets per cm3). No measurable aerosol reached the lungs during spontaneous breathing because of the efficient filtering capabilities of the turbinated nasal passages. With tracheotomy, aerosol depositions within the lung were achieved in mass quantities consistent with theoretical expectations; however, the distribution patterns were nonuniform and unpredictable. Oxygen-enhanced 19F imaging was demonstrated.

Conclusions: Perfluorocarbon aerosols of controlled size distribution can be produced at sufficient concentration with pneumatic generators for distribution to the terminal pulmonary architecture and visualization using 19F MR imaging. The potential exists for in vivo oxygen-sensitive imaging in the pulmonary system and development of sophisticated experimental animal models of systemic oxygen transport as a function of pulmonary status.