Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging Predicts Vein Wall Scarring and Statin Benefit in Murine Venous Thrombosis

Circ Cardiovasc Imaging. 2021 Mar;14(3):e011898. doi: 10.1161/CIRCIMAGING.120.011898. Epub 2021 Mar 16.


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 18F-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.

Keywords: 18F-fluorodeoxyglucose; inflammation; jugular veins; neutrophils; positron-emission tomography; post thrombotic syndrome; venous thrombosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cicatrix / diagnosis*
  • Cicatrix / etiology
  • Disease Models, Animal
  • Fluorodeoxyglucose F18 / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Positron Emission Tomography Computed Tomography / methods*
  • Radiopharmaceuticals / pharmacology
  • Veins / diagnostic imaging*
  • Venous Thrombosis / diagnosis*
  • Venous Thrombosis / etiology


  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18