Detection of Perivenous Inflammation in a Rat Model of Venous Thrombosis Using MRV

Abstract

Venous thrombosis is associated with a significant inflammatory response in the vein wall, which can be imaged noninvasively with gadolinium (Gd)-enhanced magnetic resonance venography (MRV). Interleukin-10 (IL-10), a naturally occurring anti-inflammatory cytokine, has been found to decrease the inflammatory response at the proper dosage and timing of administration. The present study determines if MRV with Gd is useful in a rat model of stasis-induced venous thrombosis to document the anti-inflammatory effects of rIL-10. Rats underwent laparotomy and ligation of the inferior vena cava (IVC). Animals were infused with rIL-10 at 2.5mug (n=6), rIL-10 at 10mug (n=6), or rIL-10 at40mug (n=6). Six animals without IVC ligation or drug infusion served as controls. Two days after thrombosis induction, the rats underwent MRV with both time-of-flight imaging and pre/post-Gd T1-weighted imaging. Inflammation was analyzed by measuring the area of Gd enhancement at the point of IVC thrombosis. Enhancement area was also measured in the distal IVC where flow persisted. All animals with IVC ligation developed thrombosis, and all control rats were free of thrombus. In areas where flow remained, the area of enhancement was 1.8 +/- 0.4 mm2, while controls demonstrated 3.8 1.0 mm2 enhancement. Enhancement was significantly greaterin all groups at the level of thrombus compared to the area of distal IVC flow and control IVCs (p<.001). Animals receiving rIL-10 at 40mug revealed the most enhancement, 32.7 +/- 6.2 mm2, while the least enhancement was noted with 2.5mug, 14.7 +/- 1.5 mm2 (p<.05). In conclusion, Gd-enhanced MRV was found useful in this rat model of stasis-induced venous thrombosis to document inflammation noninvasively and to evaluate the effects of anti-inflammatory interventions during stasis-induced IVC venous thrombosis.