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Time course of the effect of ferumoxytol on T1-relaxation times of blood, liver, myocardium, and acute infarction

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Journal of Cardiovascular Magnetic Resonance201214 (Suppl 1) :P52

https://doi.org/10.1186/1532-429X-14-S1-P52

  • Published:

Keywords

  • Myocardial Infarction
  • Chronic Kidney Disease
  • Acute Myocardial Infarction
  • Normal Myocardium
  • Acute Infarction

Background

Intravenous iron-supplementation drugs are frequently used for treatment of iron-deficiency anemia in chronic kidney disease. Some iron-agents alter tissue T1-relaxation times (T1) for days after administration, and could obscure MRI diagnosis. Conversely, these agents may have the potential to delineate pathology. We sought to investigate the T1-shortening effect of ferumoxytol and iron-dextran, determine how T1 of blood, liver, and myocardium change over time in-vivo after iron administration, and explore the utility of these agents for imaging acute myocardial infarction (MI).

Methods

We determined in-vitro T1 of ferumoxytol and iron-dextran (20mg Fe ad 500ml 0.9%NaCl). Seven dogs with acute, reperfused MI were scanned five days later on a 3.0T MRI-scanner, at which time ferumoxytol (n=5) or iron-dextran (n=2) was administered in clinically used doses (approx. 130mg iron). Inversion-recovery, gradient-echo images with various inversion-times (115-1600ms) were acquired prior to and serially after iron-injection at multiple time-points on day 1 (n=7), 2 (n=5), 3 (n=2), and 7 (n=7). T1 was determined by standard curve-fitting.

Results

In-vitro T1 of ferumoxytol and iron-dextran were 13% and 89% of 0.9%NaCl, respectively. T1 of blood, myocardium, and liver were 2027±421ms, 1384±143ms, and 806±74ms, respectively. Results for ferumoxytol were: T1 of blood dropped to 7% (p<0.001) 29±24min after ferumoxytol-injection, and fully recovered by day 2 in 3/5, and by day 7 in all animals. T1 of liver dropped to 36% (p<0.001) at 29±24min; notably, beyond 2 hours and still present at 1 week, liver-signal was attenuated by T2*-effects, which precluded calculation of T1. T1 of normal myocardium dropped to 51% (p<0.001) at 39.1±21.6min, and completely recovered by day 7 in all animals. Kinetics of ferumoxytol in MI was heterogenous, when T1 of normal myocardium was shortest, T1 of MI was the same or longer in all animals. At 2-5 hours, T1 of MI was shorter than myocardium in 3/5, longer in 1/5 (with no-reflow), and same in 1/5 animals (small MI). Based on differential kinetics of ferumoxytol in MI and normal myocardium, acute MI was visualized at some time-point in all animals. T1 for all tissues were similar before and after iron-dextran (p>0.05).

Conclusions

Ferumoxytol may affect cardiovascular MR beyond 2 days and liver MR beyond 1 week after administration of doses used clinically for iron-deficiency anemia. Unless recognized, this could affect MRI diagnosis. The differential kinetics suggest a potential use of ferumoxytol for delineation of acute MI.

Funding

Funded in part by Luitpold Pharmaceuticals, INC.
Figure 1
Figure 1

Time course of T1-times in 5 animals, that received ferumoxytol. * T1 of liver is reduced early after ferumoxytol, but after 2 hours, the extent of T1 reduction cannot be determined due to T2*-effects.

Figure 2
Figure 2

Pathology (a) and delayed enhancement image (b) 4:33 hrs after administration of ferumoxytol in an animal with acute infarction in the LAD (arrow).

Authors’ Affiliations

(1)
Duke Cardiovascular Magnetic Resonance Center, Durham, NC, USA

Copyright

© Spatz et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://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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