Rapid monitoring of iron-chelating therapy in Cooley’s anemia by magnetic resonance imaging (MRI) of myocardial ferritin iron

Abstract

We aimed to determine if a new MRI method that measures myocardial ferritin iron could detect short-term changes pro¬duced by oral iron-chelating therapy. With transfusional iron overload, almost all the excess iron is sequestered intracellularly as ferritin iron, a dispersed, soluble and rapidly mobilizable fraction, and hemosiderin iron, an aggregated, insoluble fraction that is a long-term reserve. Myocardial R2* is predominantly influenced by hemosiderin iron and changes slowly over several months, even with intensive iron-chelating therapy (Br J Hæmatol 2004; 127:348). Intracellular ferritin iron is evidently in equilibrium with the low molecular weight cytosolic iron pool (EMBO J 2006;25:5396) that can change rapidly with iron chelation. We studied 9 subjects with thalassemia major, initially after discontinuing iron chelation for one week and subsequently after resuming oral deferasirox, 20 to 30 mg/kg daily, for one week. We compared a breath-hold R2* pulse sequence (J Magn Reson Imagin 2003;18:33) and a new breath-hold fast spin-echo sequence (Kim et al., Magn Reson Med 2009; DOI:10.1002/mrm.22047) that permits calculation of RR2, a ‘reduced transverse relaxation rate’ that provides a mea¬sure of ferritin iron which is largely independent of hemosiderin iron (Magn Reson Med 2002;47:1131). The mean myocardial RR2 after stopping iron chelating therapy for one week was 25.1 ± 1.6 s-1 and decreased to 22.7 ± 1.7 s-1 (p = 0.005) after resuming deferasirox for one week. The change in mean R2* (from 64.2 ± 10.2 to 66.8 ± 10.5) was not significant. Measurement of myocardial RR2 may provide a new means of rapidly evaluating the effects of iron-chelating regimens on heart iron.