A breath-hold R2 mapping pulse sequence detects a decrease in myocardial ferritin iron after one-week of iron chelation
Journal of Cardiovascular Magnetic Resonance volume 12, Article number: O69 (2010)
In 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. The effective transverse relaxation rate (R2*) of myocardium is predominantly influenced by hemosiderin iron and, even with intensive iron-chelating therapy, changes only slowly over several months . Intracellular ferritin iron is evidently in equilibrium with the low molecular weight cytosolic iron pool  that can decrease rapidly with iron chelation. We propose to use a new breath-hold fast spin-echo (FSE)  pulse sequence that permits calculation of RR2 , a "reduced transverse relaxation rate" as a measure of myocardial ferritin iron that is largely independent of hemosiderin iron.
To use RR2 measurements to detect short-term changes in myocardial ferritin iron produced by iron-chelating therapy.
We imaged 10 patients with thalassemia major (New York; mean age = 26.9 ± 10.3 years) on a 1.5 T MR scanner (Siemens-Avanto), and another 8 patients with thalassemia (Hong Kong; mean age = 29.3 ± 8.6 years) on a 3 T scanner (Phillips-Achieva). Both sets of patients were imaged in a mid-ventricular short-axis plane of the heart at mid-diastole, initially after discontinuing iron-chelation for one week, and subsequently after resuming their usual therapy (group 1: deferasirox; group 2: deferoxamine and/or deferiprone), for one week. Three different sets of FSE data were acquired in separate breath-holds with different echo spacings (ESP). For details on the pulse sequence and its parameters, please see references [3, 5]. A standard R2* mapping pulse sequence was also performed.
For data analysis, the septum was segmented manually. R2* was calculated by non-linear least square fitting of the mono-exponential relaxation curve. The RR2 was calculated by non-linear least square fitting of the three sets of non-monoexponential relaxation curves with different ESPs .
Figure 1 shows R2* and RR2 maps of a patient after one week off and thereafter one week on iron chelation. In both groups (Table 1), the mean RR2 was significantly decreased on compared to off iron-chelating therapy (group1: 22.0 ± 5.3 s-1 vs. 24.5 ± 4.9 s-1; p < 0.01; group 2: 20.0 ± 5.6 s-1 vs. 22.1 ± 5.4 s-1; p < 0.01), whereas R2* was not different between the two states (group1: 61.1 ± 30.6 s-1 vs. 62.3 ± 27.6 s-1; group 2: 71.9 ± 43.3 s-1 vs. 74.1 ± 39.0 s-1).
This study demonstrates that a decrease in myocardial ferritin iron can be detected after as little as one week of iron-chelating therapy. Measurement of RR2 may provide a new means of rapidly monitoring the effectiveness of iron-chelating therapy.
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Grant sposor: AHA 0730143N; NIH R01-HL083309, NIH R01-DK069373, NIH R01-EB000447-07A1, NIH R01-DK069373, NIH R01-DK066251, NIH R37-DK049108, NIH R01-DK049108, GRF7794/07M, HK Children Thalassaemia Foundation (No. 2007/02).
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Kim, D., Wu, E.X., Jensen, J. et al. A breath-hold R2 mapping pulse sequence detects a decrease in myocardial ferritin iron after one-week of iron chelation. J Cardiovasc Magn Reson 12 (Suppl 1), O69 (2010). https://doi.org/10.1186/1532-429X-12-S1-O69