Magnetic resonance T1 relaxation time of venous thrombus is determined by iron processing and predicts susceptibility to lysis
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Magnetic resonance T1 relaxation time of venous thrombus is determined by iron processing and predicts susceptibility to lysis. / Saha, Prakash; Andia, Marcelo E; Modarai, Bijan; Blume, Ulrike; Humphries, Julia; Patel, Ashish S; Phinikaridou, Alkystis; Evans, Colin E; Mattock, Katherine; Grover, Steven P; Ahmad, Anwar; Lyons, Oliver T; Attia, Rizwan Q; Renné, Thomas; Premaratne, Sobath; Wiethoff, Andrea J; Botnar, René M; Schaeffter, Tobias; Waltham, Matthew; Smith, Alberto.
in: CIRCULATION, Jahrgang 128, Nr. 7, 13.08.2013, S. 729-36.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Magnetic resonance T1 relaxation time of venous thrombus is determined by iron processing and predicts susceptibility to lysis
AU - Saha, Prakash
AU - Andia, Marcelo E
AU - Modarai, Bijan
AU - Blume, Ulrike
AU - Humphries, Julia
AU - Patel, Ashish S
AU - Phinikaridou, Alkystis
AU - Evans, Colin E
AU - Mattock, Katherine
AU - Grover, Steven P
AU - Ahmad, Anwar
AU - Lyons, Oliver T
AU - Attia, Rizwan Q
AU - Renné, Thomas
AU - Premaratne, Sobath
AU - Wiethoff, Andrea J
AU - Botnar, René M
AU - Schaeffter, Tobias
AU - Waltham, Matthew
AU - Smith, Alberto
PY - 2013/8/13
Y1 - 2013/8/13
N2 - BACKGROUND: 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.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 7 days 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.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.
AB - BACKGROUND: 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.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 7 days 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.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.
KW - Animals
KW - Endothelium, Vascular
KW - Erythrocytes
KW - Fibrinolysis
KW - Humans
KW - Iron
KW - Ligation
KW - Macrophages
KW - Magnetic Resonance Imaging
KW - Male
KW - Mass Spectrometry
KW - Methemoglobin
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Knockout
KW - Nitric Oxide Synthase Type II
KW - Oxidation-Reduction
KW - Receptors, CCR2
KW - Time Factors
KW - Vena Cava, Inferior
KW - Venous Thrombosis
U2 - 10.1161/CIRCULATIONAHA.113.001371
DO - 10.1161/CIRCULATIONAHA.113.001371
M3 - SCORING: Journal article
C2 - 23820077
VL - 128
SP - 729
EP - 736
JO - CIRCULATION
JF - CIRCULATION
SN - 0009-7322
IS - 7
ER -