Abstract 12087: Noninvasive Imaging of Inflammation Using 18F-FDG PET/CT Allows in vivo Assessment of the Biological Age of Deep Venous Thrombosis
Background: The biological age of deep vein thrombosis (DVT) is a critical predictor of successful fibrinolysis. Noninvasive imaging of DVT inflammation could offer new insights into the resolution of DVT and guide the management of fibrinolytic therapy. FDG uptake is increased in lesions containing phagocytic immune cells such as macrophages and neutrophils. We hypothesized that 18F-FDG PET imaging could evaluate thrombus age via visualizing inflammatory activity in murine DVT.
Methods: C57BL/6 mice (n=20) underwent ligation of the jugular vein to induce stasis DVT and FDG-PET and CT venography was performed between day 2 to day 14. Gamma counting, immunoblotting, and histological/immunological analyses of thrombus were performed after the PET/CT imaging. To further elucidate the role of neutrophils in modulating the FDG DVT signal, antibody-based neutrophil depletion was performed in a subset of mice prior to PET/CT. SUVs and TBRs (target-to-background ratio; DVT/sham) were analyzed.
Results: DVT produced substantial, time-dependent FDG uptake, as assessed by PET/CT (SUV = 1.5 ± 0.18 (day 2-4) vs. 0.87 ± 0.06, (day 7-14), p ≤ 0.05) and well counter (%IDGT 7.23 ± 0.31 vs. 5.32 ± 0.65, p ≤ 0.05). Histological analyses demonstrated that early DVT showed 25x greater neutrophil content compared to macrophages, suggesting that neutrophils are the main cellular contributor to FDG uptake in early DVT. Neutrophil depletion decreased FDG uptake in DVT at day 2 compared with control mice (SUV = 1.24 ± 0.13 vs. 2.18 ± 0.25, p ≤ 0.05). TBRs results paralleled the SUV results. Expression levels of MMP-9 in DVT showed a similar time-dependent decrease as FDG PET.
Conclusions: FDG PET/CT imaging of experimental DVT provides information about inflammation and suggests thrombus age. Thrombus neutrophils appear to be the cellular source underlying accumulated FDG signal in early DVT. FDG PET may be able to identify early stage thrombi that are more amenable to fibrinolytic therapy.
- © 2013 by American Heart Association, Inc.