Assessment of Venous Thrombosis in Animal Models

Abstract

Deep vein thrombosis and common complications, including pulmonary embolism and post-thrombotic syndrome, represent a major source of morbidity and mortality worldwide. Experimental models of venous thrombosis have provided considerable insight into the cellular and molecular mechanisms that regulate thrombus formation and subsequent resolution. Here, we critically appraise the ex vivo and in vivo techniques used to assess venous thrombosis in these models. Particular attention is paid to imaging modalities, including magnetic resonance imaging, micro-computed tomography, and high-frequency ultrasound that facilitate longitudinal assessment of thrombus size and composition.

Keywords: histological techniques; models, animal; molecular imaging; venous thrombosis.

Figure 1. Weight and morphology of resolving murine venous thrombi

(A) Thrombus weight in the St Thomas’ model of IVC stenosis measured at days 1, 4, 7, 10 and 14 post- induction, bars represent mean ± SEM. (B) Representative micrographs of transverse thrombus sections stained with Martius scarlet blue (MSB) at days 1, 7, 14, 21 and 28 post-induction. MSB detects collagen (blue), fibrin (red) and erythrocytes (yellow), scale bars 200μm (low power) and 25μm (high power). Adapted from Saha et. al. 2013 .

Figure 2. Imaging of the resolving venous thrombus by MRI

(A) Venous phase time-of-flight scans used for imaging of the IVC, presence of thrombus results in a filling defect in the vessel which can be used to estimate thrombus volume. (B) Generation of T1 maps demonstrates a temporal shortening in T1 relaxivity (red shift) as the thrombus resolves. Adapted from Saha et. al. 2013 .

Figure 3. Visualisation of venous thrombi by high frequency ultrasound

Transverse view of (A) sham operated mouse with a patent IVC and (B) after IVC ligation with hyperechoic thrombus present in the lumen. Adapted from Aghourain et. al. 2012 .