Modeling Pulmonary Kinetics of 2-Deoxy-2-[18F]fluoro-d-glucose During Acute Lung Injury

Abstract

Rationale and objectives-Dynamic positron-emission tomography (PET) imaging of the radiotracer 2-deoxy-2-[18F]fluoro-D-glucose ( 18 F-FDG) is increasingly used to assess metabolic activity of lung inflammatory cells. To analyze the kinetics of 18 F-FDG in brain and tumor tissues the 'Sokoloff' model has been typically used. In the lungs, however, a high blood-to-parenchymal volume ratio and 18 F-FDG distribution in edematous injured tissue could require a modified model to properly describe 18 F-FDG kinetics.Material and Methods-We developed and validated a new model of lung 18 F-FDG kinetics that includes an extravascular/non-cellular compartment in addition to blood and 18 F-FDG precursor pools for phosphorylation. Parameters obtained from this model were compared with those obtained using the Sokoloff model. We analyzed dynamic PET data from 15 sheep with smoke or ventilatorinduced lung injury.Results-In the majority of injured lungs, the new model provided better fit to the data than the Sokoloff model. Rate of pulmonary 18 F-FDG net uptake and distribution volume in the precursor pool for phosphorylation correlated between the two models (R 2 = 0.98, 0.78), but were overestimated with the Sokoloff model by 17% (p < 0.05) and 16% (p < 0.0005) as compared to the new one. The range of the extravascular/non-cellular 18 F-FDG distribution volumes was up to 13% and 49% of lung tissue volume in smoke and ventilator-induced lung injury, respectively. Conclusion-The lung-specific model predicted 18 F-FDG kinetics during acute lung injury more accurately than the Sokoloff model and may provide new insights in the pathophysiology of lung injury.

Noninvasive Quantitative Assessment of Pulmonary Blood Flow with 18F-FDG PET

“…Model parameters were estimated with a generalized least squares algorithm and an autoregressive Laplacian filter (17,20). For each timeactivity curve, model rate constants and FB were computed from the model with the best fit across the data (Appendix).…”

“…Lung regional 18 F-FDG kinetics and the 18 F-FDG image-derived input function were fitted to both the Sokoloff 3-compartment model (16) and a 4-compartment model incorporating an extravascular noncellular compartment (TEC model) ( Fig. 1) (17). The TEC model may be more relevant than the Sokoloff model for edematous lung regions because the former accounts for an (additional) extravascular noncellular compartment spatially disconnected from cells trapping 18 F-FDG.…”

“…Two milliliters of blood were taken serially through a systemic arterial line during 18 F-FDG image acquisition. The plasma radioactivity was measured in a well counter cross-calibrated with the PET camera, and the plasma activities of samples taken at 3 and 50 min after the start of 18 F-FDG injection were used to calibrate the blood-pool region of interest (ROI) located in the left ventricle and to obtain an image-derived input function taking into account partial-volume and spillover effects (17).…”

“…Such activity has been taken as a surrogate for neutrophil activation during acute lung injury (ALI) (13,14). In addition to the net 18 F-FDG uptake rate within the lung, some compartmental modeling techniques (16,17) estimate the regional fraction of blood (FB), accounting for the contribution of intravascular 18 F-FDG to pulmonary radioactivity assessed by PET within each lung region. Because the spatial resolution of PET is relatively poor, vascular structures are included within lung regions of interest, and FB represents the volume of blood relative to the total volume of a lung region and is usually expressed in milliliters of blood per 100 milliliters of lung.…”

Imaging Pulmonary Inflammation

“…However, the exact mechanisms by which ARDS develops have yet to be elucidated. 18 F-FDG has been used extensively to study the kinetics of neutrophil activation and recruitment in ARDS in preclinical models (12,62). Several small studies have further evaluated 18 F-FDG PET in patients with ARDS or at risk of developing ARDS.…”