Spatial Heterogeneity of Lung Strain and Aeration and Regional Inflammation During Early Lung Injury Assessed with PET/CT

Introduction: Spatial heterogeneity of lung aeration and strain (change volume/resting volume) occurs at microscopic levels and contributes to lung injury. Yet, it is mostly assessed with histograms or large regions-of-interest. Spatial heterogeneity could also influence regional gene expression. We used positron emission tomography (PET)/computed tomography (CT) to assess the contribution of different length-scales to mechanical heterogeneity and to direct lung injury biological pathway identification. Materials and Methods: Sheep exposed to mild (n = 5, supine and n = 3, prone) and moderate (n = 6, supine) systemic endotoxemia were protectively ventilated. At baseline, 6 hours and 20 hours length-scale analysis was applied to aeration in CT (mild groups) and PET transmission (moderate group) scans; and voxel-level strain derived from image registration of end-inspiratory and end-expiratory CTs (mild). 2-deoxy-2-[(18)F]fluoro-d-glucose ( ¹⁸ F-FDG)-PET kinetics parameters in ventral and dorsal regions were correlated with tissue microarray gene expression (moderate). Results: While aeration and strain heterogeneity were highest at 5–10 mm length-scales, larger length-scales contained a higher fraction of strain than aeration heterogeneity. Contributions of length-scales >5–10 mm to aeration and strain heterogeneity increased as lung injury progressed (p < 0.001) and were higher in supine than prone animals. Genes expressed with regional correlation to ¹⁸ F-FDG-PET kinetics (|r| = 0.81 [0.78–0.85]) yielded pathways associated with immune system activation and fluid clearance. Conclusion: Normal spatial heterogeneity of aeration and strain suggest larger anatomical and functional determinants of lung strain than aeration heterogeneity. Lung injury and supine position increase the contribution of larger length-scales. ¹⁸ F ⁻ FDG-PET-based categorization of gene expression results in known and novel biological pathways relevant to lung injury.