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Original research article
Ferumoxytol-enhanced magnetic resonance imaging assessing inflammation after myocardial infarction
  1. Colin G Stirrat1,
  2. Shirjel R Alam1,
  3. Thomas J MacGillivray2,3,
  4. Calum D Gray2,3,
  5. Marc R Dweck1,
  6. Jennifer Raftis1,
  7. William SA Jenkins1,
  8. William A Wallace4,
  9. Renzo Pessotto5,
  10. Kelvin HH Lim5,
  11. Saeed Mirsadraee2,
  12. Peter A Henriksen1,
  13. Scott IK Semple1,2,
  14. David E Newby1,2
  1. 1 British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
  2. 2 Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK
  3. 3 Clinical Research Facility, University of Edinburgh, Edinburgh, USA
  4. 4 Department of Pathology, University of Edinburgh, Edinburgh, UK
  5. 5 Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK
  1. Correspondence to Dr Colin G Stirrat, British Heart Foundation/University Centre for Cardiovascular Science, Room SU 305, Chancellor’s Building, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK; colin.stirrat{at}ed.ac.uk

Abstract

Objectives Macrophages play a central role in the cellular inflammatory response to myocardial infarction (MI) and predict subsequent clinical outcomes. We aimed to assess temporal changes in cellular inflammation and tissue oedema in patients with acute MI using ultrasmallsuperparamagnetic particles of iron oxide (USPIO)-enhanced MRI.

Methods Thirty-one patients were recruited following acute MI and followed up for 3 months with repeated T2 and USPIO-enhanced T2*-mapping MRI. Regions of interest were categorised into infarct, peri-infarct and remote myocardial zones, and compared with control tissues.

Results Following a single dose, USPIO enhancement was detected in the myocardium until 24 hours (p<0.0001). Histology confirmed colocalisation of iron and macrophages within the infarcted, but not the non-infarcted, myocardium. Following repeated doses, USPIO uptake in the infarct zone peaked at days 2–3, and greater USPIO uptake was detected in the infarct zone compared with remote myocardium until days 10–16 (p<0.05). In contrast, T2-defined myocardial oedema peaked at days 3–9 and remained increased in the infarct zone throughout the 3-month follow-up period (p<0.01).

Conclusion Myocardial macrophage activity can be detected using USPIO-enhanced MRI in the first 2 weeks following acute MI. This observed pattern of cellular inflammation is distinct, and provides complementary information to the more prolonged myocardial oedema detectable using T2 mapping. This imaging technique holds promise as a non-invasive method of assessing and monitoring myocardial cellular inflammation with potential application to diagnosis, risk stratification and assessment of novel anti-inflammatory therapeutic interventions.

Trial registration number Trial registration number: 14663. Registered on UK Clinical Research Network (http://public.ukcrn.org.uk) and also ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02319278?term=DECIFER&rank=2).

  • Cardiac
  • MRI
  • Myocardial Infarction
  • Molecular Imaging
  • Inflammation
  • USPIO

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • Funding This work was supported by the British Heart Foundation (FS/12/83). CGS is supported by the Chief Scientist Office (ETM/266). SA and DEN are supported by the British Heart Foundation (FS/12/83; CH/09/002). DEN is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Wellcome Trust Clinical Research Facility and the Clinical ResearchImaging Centre are supported by NHS Research Scotland (NRS) through NHS Lothian.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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