Magnetic Resonance T 1 Relaxation Time of Venous Thrombus Is Determined by Iron Processing and Predicts Susceptibility to Lysis

Abstract

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 Fe 3+ , 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 Fe 3+ 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 Fe 3+ form. Quantification of T 1 relaxation time appears to be a good predictor of the success of thrombolysis.