Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging Predicts Vein Wall Scarring and Statin Benefit in Murine Venous Thrombosis. (17th March 2021)

• Record Type: Journal Article
• Authors: Kessinger, Chase W.; Qi, Guanming; Hassan, Malek Z.O.; Henke, Peter K.; Tawakol, Ahmed; Jaffer, Farouc A.
• Is Part Of: Circulation. Volume 14:Number 3(2021)
• Page Start: e011898
• Publication Date: 2021-03-17
• Subjects: 18F-fluorodeoxyglucose -- inflammation -- jugular veins -- neutrophils -- positron-emission tomography -- post thrombotic syndrome -- venous thrombosis; Cardiovascular system -- Imaging -- Periodicals; Heart -- Imaging -- Periodicals; 616.1075405
• DOI: 10.1161/CIRCIMAGING.120.011898
• Languages: English
• ISSNs: 1941-9651

Abstract

Abstract : Supplemental Digital Content is available in the text. Abstract : Background: The postthrombotic syndrome is a common, often morbid sequela of venous thrombosis (VT) that arises from thrombus persistence and inflammatory scarring of juxtaposed vein walls and valves. Noninvasive 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can measure neutrophil inflammation in VT. Here, we hypothesized (1) early fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) VT inflammation can predict subsequent vein wall scarring (VWS) and (2) statin therapy can reduce FDG-PET VT inflammation and subsequent VWS. Methods: C57BL/6J mice (n=75) underwent induction of stasis-induced VT of the inferior vena cava or jugular vein. Inferior vena cava VT mice (n=44) were randomized to daily oral rosuvastatin 5 mg/kg or saline starting at day −1. Subgroups of mice then underwent FDG-PET/CT 2 days after VT induction. On day 14, a subset of mice was euthanized, and VWS was assessed via histology. In vitro studies were further performed on bone marrow-derived neutrophils. Results: Statin therapy reduced early day 2 FDG-PET VT inflammation, thrombus neutrophil influx, and plasma IL (interleukin)-6 levels. At day 14, statin therapy reduced VWS but did not affect day 2 thrombus mass, cholesterol, or white blood counts, nor reduce day 2 glucose transporter 1 or myeloperoxidase expression in thrombus or in isolated neutrophils. In survival studies, the day 2 FDG-PET VT inflammation signal as measured by mean and maximum standardized uptake values predicted the extent of day 14 VWS (area under the receiver operating characteristic curve =0.82) with a strong correlation coefficient ( r ) of r =0.73 and r =0.74, respectively. Mediation analyses revealed that 40% of the statin-induced VWS reduction was mediated by reductions in VT inflammation as quantified by FDG-PET. Conclusions: Early noninvasive FDG-PET/CT imaging of VT inflammation predicts the magnitude of subsequent VWS and may provide a new translatable approach to identify individuals at risk for postthrombotic syndrome and to assess anti-inflammatory postthrombotic syndrome therapies, such as statins.