Magnetic Resonance T1 Relaxation Time of Venous Thrombus Is Determined by Iron Processing and Predicts Susceptibility to Lysis

Background-The magnetic resonance longitudinal relaxation time (T-1) changes with thrombus age in humans. In this study, we investigate the possible mechanisms that give rise to the T-1 signal in venous thrombi and whether changes in T-1 relaxation time are informative of the susceptibility to lysis. Methods and Results-Venous thrombosis was induced in the vena cava of BALB/C mice, and temporal changes in T-1 relaxation time correlated with thrombus composition. The mean T-1 relaxation time of thrombus was shortest at 7days following thrombus induction and returned to that of blood as the thrombus resolved. T-1 relaxation time was related to thrombus methemoglobin formation and further processing. Studies in inducible nitric oxide synthase (iNOS(-/-))-deficient mice revealed that inducible nitric oxide synthase mediates oxidation of erythrocyte lysis-derived iron to paramagnetic Fe3+, which causes thrombus T-1 relaxation time shortening. Studies using chemokine receptor-2-deficient mice (Ccr2(-/-)) revealed that the return of the T-1 signal to that of blood is regulated by removal of Fe3+ by macrophages that accumulate in the thrombus during its resolution. Quantification of T-1 relaxation time was a good predictor of successful thrombolysis with a cutoff point of <747 ms having a sensitivity and specificity to predict successful lysis of 83% and 94%, respectively. Conclusions-The source of the T-1 signal in the thrombus results from the oxidation of iron (released from the lysis of trapped erythrocytes in the thrombus) to its paramagnetic Fe3+ form. Quantification of T-1 relaxation time appears to be a good predictor of the success of thrombolysis.