Improving pulmonary perfusion assessment by dynamic contrast-enhanced computed tomography in an experimental lung injury model.

Pulmonary perfusion has been poorly characterized in acute respiratory distress syndrome (ARDS). Optimizing protocols to measure pulmonary blood flow (PBF) via dynamic contrast-enhanced (DCE) computed tomography (CT) could improve understanding of how ARDS alters pulmonary perfusion. In this study, comparative evaluations of injection protocols and tracer-kinetic analysis models were performed based on DCE-CT data measured in ventilated pigs with and without lung injury. Ten Yorkshire pigs (five with lung injury, five healthy) were anesthetized, intubated, and mechanically ventilated; lung injury was induced by bronchial hydrochloric acid instillation. Each DCE-CT scan was obtained during a 30-s end-expiratory breath-hold. Reproducibility of PBF measurements was evaluated in three pigs. In eight pigs, undiluted and diluted Isovue-370 were separately injected to evaluate the effect of contrast viscosity on estimated PBF values. PBF was estimated with the peak-enhancement and the steepest-slope approach. Total-lung PBF was estimated in two healthy pigs to compare with cardiac output measured invasively by thermodilution in the pulmonary artery. Repeated measurements in the same animals yielded a good reproducibility of computed PBF maps. Injecting diluted isovue-370 resulted in smaller contrast-time curves in the pulmonary artery (P < 0.01) and vein (P < 0.01) without substantially diminishing peak signal intensity (P = 0.46 in the pulmonary artery) compared with the pure contrast agent since its viscosity is closer to that of blood. As compared with the peak-enhancement model, PBF values estimated by the steepest-slope model with diluted contrast were much closer to the cardiac output (R2 = 0.82) as compared with the peak-enhancement model. DCE-CT using the steepest-slope model and diluted contrast agent provided reliable quantitative estimates of PBF.NEW & NOTEWORTHY Dynamic contrast-enhanced CT using a lower-viscosity contrast agent in combination with tracer-kinetic analysis by the steepest-slope model improves pulmonary blood flow measurements and assessment of regional distributions of lung perfusion.

Micro-autoradiographic assessment of cell types contributing to 2-deoxy-2-[(18)F]fluoro-D-glucose uptake during ventilator-induced and endotoxemic lung injury.

PURPOSE: The aim of the study was to use micro-autoradiography to investigate the lung cell types responsible for 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake in murine models of acute lung injury (ALI). PROCEDURES: C57/BL6 mice were studied in three groups: controls, ventilator-induced lung injury (VILI), and endotoxin. VILI was produced by high tidal volumes and zero end-expiratory pressure and endotoxin ALI, by intranasal administration. Following FDG injection, the lungs were processed and exposed to autoradiographic emulsion. Grain density over cells was used to quantify FDG uptake. RESULTS: Neutrophils, macrophages, and type 2 epithelial cells presented higher grain densities during VILI and endotoxin ALI than controls. Remarkably, cell grain density in specific cell types was dependent on the injury mechanism. Whereas macrophages showed high grain densities during endotoxin ALI, similar to those exhibited by neutrophils, type 2 epithelial cells demonstrated the second highest grain density (with neutrophils as the highest) during VILI. CONCLUSIONS: In murine models of VILI and endotoxin ALI, FDG uptake occurs not only in neutrophils but also in macrophages and type 2 epithelial cells. FDG uptake by individual cell types depends on the mechanism underlying ALI.

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.