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- Title
Rapid monitoring of iron-chelating therapy in thalassemia major by a new cardiovascular MR measure: the reduced transverse relaxation rate.
- Authors
Kim, Daniel; Jensen, Jens H.; Wu, Ed X.; Feng, Li; Au, Wing-Yan; Cheung, Jerry S.; Ha, Shau-Yin; Sheth, Sujit S.; Brittenham, Gary M.
- Abstract
In iron overload, almost all the excess iron is stored intracellularly as rapidly mobilizable ferritin iron and slowly exchangeable hemosiderin iron. Increases in cytosolic iron may produce oxidative damage that ultimately results in cardiomyocyte dysfunction. Because intracellular ferritin iron is evidently in equilibrium with the low-molecular-weight cytosolic iron pool, measurements of ferritin iron potentially provide a clinically useful indicator of changes in cytosolic iron. The cardiovascular magnetic resonance (CMR) index of cardiac iron used clinically, the effective transverse relaxation rate ( R2*), is principally influenced by hemosiderin iron and changes only slowly over several months, even with intensive iron-chelating therapy. Another conventional CMR index of cardiac iron, the transverse relaxation rate ( R2), is sensitive to both hemosiderin iron and ferritin iron. We have developed a new MRI measure, the 'reduced transverse relaxation rate' ( RR2), and have proposed in previous studies that this measure is primarily sensitive to ferritin iron and largely independent of hemosiderin iron in phantoms mimicking ferritin iron and human liver explants. We hypothesized that RR2 could detect changes produced by 1 week of iron-chelating therapy in patients with transfusion-dependent thalassemia. We imaged 10 patients with thalassemia major at 1.5 T in mid-ventricular short-axis planes of the heart, initially after suspending iron-chelating therapy for 1 week and subsequently after resuming oral deferasirox. After resuming iron-chelating therapy, significant decreases were observed in the mean myocardial RR2 (7.8%, p < 0.01) and R2 (5.5%, p < 0.05), but not in R2* (1.7%, p > 0.90). Although the difference between changes in RR2 and R2 was not significant ( p > 0.3), RR2 was consistently more sensitive than R2 (and R2*) to the resumption of iron-chelating therapy, as judged by the effect sizes of relaxation rate differences detected. Although further studies are needed, myocardial RR2 may be a promising investigational method for the rapid assessment of the effects of iron-chelating therapy in the heart. Copyright © 2010 John Wiley & Sons, Ltd.
- Publication
NMR in Biomedicine, 2011, Vol 24, Issue 7, p771
- ISSN
0952-3480
- Publication type
Article
- DOI
10.1002/nbm.1639