Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging Predicts Vein Wall Scarring and Statin Benefit in Murine Venous Thrombosis.
Circ Cardiovasc Imaging
; 14(3): e011898, 2021 03.
Article
in En
| MEDLINE
| ID: mdl-33724049
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 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Veins
/
Cicatrix
/
Fluorodeoxyglucose F18
/
Venous Thrombosis
/
Positron Emission Tomography Computed Tomography
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Circ Cardiovasc Imaging
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
/
DIAGNOSTICO POR IMAGEM
Year:
2021
Document type:
Article