In Vivo Magnetization Transfer and Diffusion-Weighted Magnetic Resonance Imaging Detects Thrombus Composition in a Mouse Model of Deep Vein Thrombosis

Abstract

Background— Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis. Methods and Results— Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; P ANOVA <0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus ( r =0.70; P <0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10 −3 mm 2 /s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10 −3 mm 2 /s]). Conclusions— MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention.