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 (T1) changes with thrombus age in man. In this study, we investigate 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.
Methods and Results—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 iNOS 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 cut-off point of less than 747ms having a sensitivity and specificity to predict successful lysis of 83% and 94% respectively.
Conclusions—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.
- Received January 22, 2013.
- Revision received June 18, 2013.
- Accepted June 24, 2013.