Ferumoxytol-enhanced magnetic resonance imaging in acute myocarditis

Abstract

Objectives: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect tissue-resident macrophage activity and identify cellular inflammation within tissues. We hypothesised that USPIO-enhanced MRI would provide a non-invasive imaging technique that would improve the diagnosis and management of patients with acute myocarditis.

Methods: Ten volunteers and 14 patients with suspected acute myocarditis underwent T2, T2* and late gadolinium enhancement (LGE) 3T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Myocardial oedema and USPIO enhancement were determined within areas of LGE as well as throughout the myocardium.

Results: Myocarditis was confirmed in nine of the 14 suspected cases of myocarditis. There was greater myocardial oedema in regions of LGE in patients with myocarditis when compared with healthy volunteer myocardium (T2 value, 57.1±5.3 vs 46.7±1.6 ms, p<0.0001). There was no demonstrable difference in USPIO enhancement between patients and volunteers even within regions displaying LGE (change in R2*, 35.0±15.0 vs 37.2±9.6 s-1, p>0.05). Imaging after 3 months in patients with myocarditis revealed a reduction in volume of LGE, a reduction in oedema measures within regions displaying LGE and improvement in ejection fraction (mean -19.7 mL, 95% CI (-0.5 to -40.0)), -5.8 ms (-0.9 to -10.7) and +6% (0.5% to 11.5%), respectively, p<0.05 for all).

Conclusion: In patients with acute myocarditis, USPIO-enhanced MRI does not provide additional clinically relevant information to LGE and T2 mapping MRI. This suggests that tissue-resident macrophages do not provide a substantial contribution to the myocardial inflammation in this condition.Clinical trial registration NCT02319278; Results.

Keywords: MRI; USPIO.; cardiac; inflammation; myocarditis.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Images of patient with myocarditis. Three chamber and basal short-axis images of a patient with myocarditis displaying patchy posterolateral late gadolinium enhancement (LGE) (white regions, arrowed) that correspond to oedematous regions of myocardium on the T2 map (lighter regions, arrowed). There is no uptake of ultrasmall superparamagnetic particles of iron oxide (USPIO) in the post-USPIO R2* maps; corresponding regions may even have lower R2* in this patient. Myocardial oedema appears to normalise but subtle LGE remains at 3 months.

Figure 2

Myocardial USPIO enhancement vs Oedema at Baseline. Changes in myocardial R2* due to USPIO accumulation (A, left) and myocardial oedema by T2 mapping (B, right) are shown in healthy volunteers (HV) and patients with myocarditis (M) using panmyocardial average, and further limited to regions displaying LGE in patients with myocarditis (M LGE+). There were no significant differences in ΔR2* due to USPIO accumulation between all groups (p>0.05 for all). There was no difference in panmyocardial T2 between volunteers with patients with myocarditis. Myocardial regions displaying LGE (M LGE+) had greater T2 than the panmyocardial value for healthy volunteers and myocarditis patients (****p

Figure 3

Changes on repeat imaging at 3 months in patients with myocarditis. There was no significant (ns) difference in ultrasmall superparamagnetic particles of iron oxide uptake between baseline and 3 months in both panmyocardium (A) and in regions displaying late gadolinium enhancement (LGE) (B). There was no difference in panmyocardial T2 (C) over 3 months. T2 in regions displaying LGE (D) reduced, as did the volume of LGE (E) over the 3-month period. There was an increase in ejection fraction (EF) between baseline and 3 months (F); *p