Abstract 16: FDG-PET/CT Enables the Detection of Recurrent, Same-Site Deep Vein Thrombosis by Illuminating Recently Formed Neutrophil-Rich Thrombus

Abstract

Background: Specific detection of recurrent deep vein thrombosis (DVT) is a challenging clinical problem. As DVT formation and resolution are inflammatory processes, we experimentally investigated whether noninvasive 18F-fluorodeoxyglucose (FDG)-PET imaging could identify inflamed, recently formed thrombi and thereby improve the diagnosis of recurrent DVT. Methods: We established a stasis-induced DVT model in murine jugular veins and also a novel model of recurrent stasis DVT in mice. C57BL/6 mice (n = 30) underwent ligation of the jugular vein to induce stasis DVT. FDG-PET/CT was performed at DVT timepoints of day 2, 4, 7, 14, or 2+16 (same-site recurrent day 2 DVT overlying a 16 days old DVT). Antibody-based neutrophil depletion was performed in a subset of mice prior to DVT formation and FDG-PET/CT. In a clinical study, 38 patients with lower extremity DVT or controls undergoing FDG-PET were retrospectively analyzed. Results: Stasis DVT demonstrated that the highest FDG signal occurred day 2, followed by a time-dependent decrease (p<0.05). Histological analyses demonstrated that thrombus neutrophils (p<0.01), but not macrophages, correlated with thrombus PET signal intensity. Neutrophil depletion decreased FDG signals in day 2 DVT compared to that of control mice (p<0.05). Recurrent DVT demonstrated significantly higher FDG uptake than organized day 14 DVT (p<0.05). The FDG DVT signal in patients also exhibited a time-dependent decrease (p<0.05). Recurrent day 2 DVT showed neutrophil-dominant infiltration pattern with few macrophages, similar to standalone day 2 DVT. Conclusions: Noninvasive FDG-PET/CT identifies neutrophil-dependent thrombus inflammation in murine DVT, and demonstrates a time-dependent signal in both murine and clinical DVT. FDG-PET/CT may offer a molecular imaging strategy to accurately diagnose recurrent DVT.