FDG-PET/CT Enables the Detection of Recurrent Same-Site Deep Vein Thrombosis by Illuminating Recently Formed, Neutrophil-Rich Thrombus
Background—Accurate detection of recurrent same-site deep vein thrombosis (DVT) is a challenging clinical problem. As DVT formation and resolution are associated with a preponderance of inflammatory cells, we investigated whether noninvasive 18F-fluorodeoxyglucose (FDG)-PET imaging could identify inflamed, recently formed thrombi and thereby improve the diagnosis of recurrent DVT.
Methods and Results—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=35) 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 DVT at day 2 overlying a primary DVT at day 16). 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 analyzed. Stasis DVT demonstrated that the highest FDG signal occurred at 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 controls (p=0.03). Recurrent DVT demonstrated significantly higher FDG uptake than organized day 14 DVT (p=0.03). The FDG DVT signal in patients also exhibited a time-dependent decrease (p<0.01).
Conclusions—Noninvasive FDG-PET/CT identifies neutrophil-dependent thrombus inflammation in murine DVT, and demonstrates a time-dependent signal decrease in both murine and clinical DVT. FDG-PET/CT may offer a molecular imaging strategy to accurately diagnose recurrent DVT.
- recurrent DVT
- molecular imaging
- deep vein thrombosis
- recurrent event
- positron emission tomography
- Received January 27, 2014.
- Revision received June 16, 2014.
- Accepted July 18, 2014.