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A breath-hold R2 mapping pulse sequence detects a decrease in myocardial ferritin iron after one-week of iron chelation

Introduction

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 [1]. Intracellular ferritin iron is evidently in equilibrium with the low molecular weight cytosolic iron pool [2] that can decrease rapidly with iron chelation. We propose to use a new breath-hold fast spin-echo (FSE) [3] pulse sequence that permits calculation of RR2 [4], a "reduced transverse relaxation rate" as a measure of myocardial ferritin iron that is largely independent of hemosiderin iron.

Purpose

To use RR2 measurements to detect short-term changes in myocardial ferritin iron produced by iron-chelating therapy.

Methods

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 [6].

Results

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).

Figure 1
figure1

(Left column) R 2 * and (right column) RR 2 maps: (top row) discontinuing chelation for one week; (bottom row) resuming chelation for one week.

Conclusion

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.

Table 1 R2* and RR2 values of two groups after 1 week off and thereafter 1 week on iron chelation

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Acknowledgements

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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Correspondence to Daniel Kim.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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, O69 (2010). https://doi.org/10.1186/1532-429X-12-S1-O69

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Keywords

  • Thalassemia
  • Iron Chelation
  • Deferoxamine
  • Relaxation Curve
  • Deferasirox