New Frontiers in Functional and Molecular Imaging of the Acutely Injured Lung: Pathophysiological Insights and Research Applications.

This review focuses on the advances in the understanding of the pathophysiology of ventilator-induced and acute lung injury that have been afforded by technological development of imaging methods over the last decades. Examples of such advances include the establishment of regional lung mechanical strain as a determinant of ventilator-induced lung injury, the relationship between alveolar recruitment and overdistension, the regional vs. diffuse nature of pulmonary involvement in acute respiratory distress syndrome (ARDS), the identification of the physiological determinants of the response to recruitment interventions, and the pathophysiological significance of metabolic alterations in the acutely injured lung. Taken together, these advances portray multimodality imaging as the next frontier to both advance knowledge of the pathophysiology of these conditions and to tailor treatment to the individual patient's condition.

Image-derived input function for assessment of 18F-FDG uptake by the inflamed lung.

UNLABELLED: Pulmonary uptake of (18)F-FDG assessed with PET has been used to quantify the metabolic activity of inflammatory cells in the lung. This assessment involves modeling of tracer kinetics and knowledge of a time-activity curve in pulmonary artery plasma as an input function, usually acquired by manual blood sampling. This paper presents and validates a method to accurately derive an input function from a blood-pool region of interest (ROI) defined in dynamic PET images. METHODS: The method is based on a 2-parameter model describing the activity of blood and that from spillover into the time-activity curve for the ROI. The model parameters are determined using an iterative algorithm, with 2 blood samples used to calibrate the raw PET-derived activity data. We validated both the 2-parameter model and the method to derive a quantitative input function from ROIs defined for the cavities of the right and left heart and for the descending aorta by comparing them against the time-activity curve obtained by manual blood sampling from the pulmonary artery in lungs with acute inflammation. RESULTS: The model accurately described the time-activity curve from sampled blood. The 2-sample calibration method provided an efficient algorithm to derive input functions that were virtually identical to those sampled manually, including the fast kinetics of the early phase. The (18)F-FDG uptake rates in acutely injured lungs obtained using this method correlated well with those obtained exclusively using manual blood sampling (R(2) > 0.993). Within some bounds, the model was found quite insensitive to the timing of calibration blood samples or the exact definition of the blood-pool ROIs. CONCLUSION: Using 2 mixed venous blood samples, the method accurately assesses the entire time course of the pulmonary (18)F-FDG input function and does not require the precise geometry of a specific blood-pool ROI or a population-based input function. This method may substantially facilitate studies involving modeling of pulmonary (18)F-FDG in patients with viral or bacterial infections, pulmonary fibrosis, and chronic obstructive pulmonary disease.