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The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [18F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [18F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome.Prospective laboratory investigation.A university animal research laboratory.Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls.Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [18F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.[18F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [18F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [18F]fluoro-2-deoxy-D-glucose uptakes similar to controls.The present findings suggest that normally and poorly aerated regions—corresponding to intermediate gravitational zones—are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.