Early Assessment of Pulmonary Inflammation by 19 F MRI In Vivo

Abstract

Background— Emulsified perfluorocarbons (PFCs) are preferentially phagocytized by monocytes/macrophages and are readily detected by ¹⁹F MRI. This study tests the hypothesis that ¹⁹F MRI can be used to quantitate pulmonary inflammation by tracking of infiltrating PFC-loaded monocytes. Methods and Results— Pneumonia was induced in mice by intratracheal instillation of lipopolysaccharides (LPS) followed by intravenous injection of PFCs. Whereas regular ¹H MRI provided no evidence of lung injury 24 hours after LPS, the concurrent ¹⁹F images clearly show PFC accumulation in both pulmonary lobes. Imaging at 48 hours after LPS revealed signals in ¹H images at the same location as the 24-hour ¹⁹F signals. Thus, progressive pneumonia was first predicted by ¹⁹F MRI early after PFC administration. Without LPS, at no time were ¹⁹F signals observed within the lung. Histology and fluorescence-activated cell sorting (FACS) combined with ¹⁹F MRI confirmed the presence of infiltrating PFC-loaded monocytes/macrophages after LPS challenge. Additional experiments with graded doses of LPS demonstrated that ¹⁹F signal intensity strongly correlated with both LPS dose and pathological markers of lung inflammation. In separate studies, dexamethasone and CGS21680 (adenosine 2A receptor agonist) were used to demonstrate the ability of ¹⁹F MRI to monitor anti-inflammatory therapies. Conclusions— PFCs serve as a contrast agent for the prognostic and quantitative assessment of pulmonary inflammation by in vivo ¹⁹F MRI, which is characterized by a high degree of specificity due to the lack of any ¹⁹F background. Because PFCs are biochemically inert, this approach may also be suitable for human applications.