The magnetic resonance longitudinal relaxation time (T₁) changes with thrombus age in humans. In this study, we investigate the possible mechanisms that give rise to the T₁ signal in venous thrombi and whether changes in T₁ relaxation time are informative of the susceptibility to lysis.

Venous thrombosis was induced in the vena cava of BALB/C mice, and temporal changes in T₁ relaxation time correlated with thrombus composition. The mean T₁ relaxation time of thrombus was shortest at 7days following thrombus induction and returned to that of blood as the thrombus resolved. T₁ 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 T₁ relaxation time shortening. Studies using chemokine receptor-2–deficient mice (Ccr2^−/−) revealed that the return of the T₁ signal to that of blood is regulated by removal of Fe³⁺ by macrophages that accumulate in the thrombus during its resolution. Quantification of T₁ 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.

The source of the T₁ 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 T₁ relaxation time appears to be a good predictor of the success of thrombolysis.