Quantitative magnetic particle imaging monitors pulmonary vascular permeability in vivo

Increased pulmonary vascular permeability is a characteristic feature of acute lung injury and some chronic lung diseases. Currently there are no established methods to visualize pulmonary vascular permeability change in vivo in in both research and clinical settings. Terminal assays such as Evans Blue test, lung wet/dry ratio, and bronchoalveolar lavage fluid (BALF) total protein test lack the capability of monitoring the dynamics of vascular injury during disease progression. In this study, we used magnetic particle imaging (MPI)-CT dual-modality imaging combined with quantitative image analysis to noninvasively visualize and evaluate pulmonary vascular permeability in vivo in animal models. Oleic acid (OA) induced acute respiratory distress syndrome (ARDS) model was used for imaging. Based on the in vivo 3D MPI-CT images, we defined pulmonary SPIO extravasation index (SEI) to evaluate the vascular permeability. Significantly increased SEI was observed in the ARDS mice, which correlated well with ex vivo imaging findings. Moreover, quantitative imaging results were validated by ex vivo Evans Blue test, lung wet/dry ratio, BALF total protein concentration measurements and H&E histology. Our results suggest that 3D quantitative MPI-CT can be used to evaluate pulmonary vascular permeability, providing a noninvasive tool to monitor the dynamic change of pulmonary injury in vivo.