Early Assessment of Pulmonary Inflammation by F MRI In Vivo

Background—Emulsified perfluorocarbons (PFCs) are preferentially phagocytized by monocytes/macrophages and are readily detected by 19 F MRI. This study tests the hypothesis that 19 F 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 1 H MRI provided no evidence of lung injury 24 hours after LPS, the concurrent 19 F images clearly show PFC accumulation in both pulmonary lobes. Imaging at 48 hours after LPS revealed signals in 1 H images at the same location as the 24-hour 19 F signals. Thus, progressive pneumonia was first predicted by 19 F MRI early after PFC administration. Without LPS, at no time were 19 F signals observed within the lung. Histology and fluorescence-activated cell sorting (FACS) combined with 19 F MRI confirmed the presence of infiltrating PFC-loaded monocytes/macrophages after LPS challenge. Additional experiments with graded doses of LPS demonstrated that 19 F 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 19 F 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 19 F MRI, which is characterized by a high degree of specificity due to the lack of any 19 F background. Because PFCs are biochemically inert, this approach may also be suitable for human applications. I nflammation is a crucial factor in many clinical lung disorders including ventilator-induced lung injury, chronic obstructive pulmonary disease, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). 1,2 ALI and ARDS determine to a great extent morbidity and mortality in critically ill patients with septic, posttrau-matic, hemorrhagic, or cardiogenic shock. State-of-the-art diagnosis of acute lung injury is performed by blood gas analysis, and supporting imaging information is typically provided by conventional chest radiography or rarely by computed tomography. 3 Especially in cardiogenic shock or after high-volume treatment, data obtained by these modalities are sometimes difficult to interpret because images reveal bilateral opacities of the lung that can represent interstitial or alveolar fluid accumulation caused by cardiac congestion, fluid overload, or beginning pulmonary inflammation and ALI. Although serum markers such as acute phase proteins and inflammatory cytokines such as procalcitonin, C-reactive protein, …