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Published on: June 20, 2014
Ferumoxytol-enhanced magnetic resonance imaging assessing inflammation after myocardial infarction
Colin G Stirrat1, Shirjel R Alam1, Thomas J MacGillivray2,3
1British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
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).
Insights
This study shows ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect myocardial macrophage activity within 2 weeks of acute myocardial infarction (MI). This imaging method offers a new way to monitor inflammation after MI.
Area of Science:
- Cardiovascular Imaging
- Inflammation Research
- Biomedical Engineering
Background:
- Macrophages are key in myocardial infarction (MI) inflammatory response and predict outcomes.
- Assessing temporal changes in cellular inflammation and edema post-MI is crucial.
Purpose of the Study:
- To evaluate ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI for assessing temporal changes in cellular inflammation and tissue edema in acute MI patients.
- To correlate USPIO uptake with macrophage activity and T2 mapping with myocardial edema.
Main Methods:
- Thirty-one acute MI patients underwent serial USPIO-enhanced T2*-mapping and T2-mapping MRI for 3 months.
- Myocardial regions (infarct, peri-infarct, remote) were analyzed, with histology confirming USPIO-macrophage colocalization.
- Temporal changes in USPIO uptake and T2 signal were compared between zones.
Main Results:
- USPIO enhancement was detectable in the myocardium for up to 24 hours post-administration.
- Histology confirmed USPIO colocalization with macrophages in the infarct zone.
- USPIO uptake peaked at days 2-3 and remained elevated in the infarct zone until days 10-16.
- Myocardial edema, assessed by T2 mapping, peaked at days 3-9 and persisted for 3 months.
Conclusions:
- USPIO-enhanced MRI can detect myocardial macrophage activity within 2 weeks post-MI.
- This technique provides distinct, complementary information to T2 mapping of edema.
- USPIO-enhanced MRI shows promise for non-invasive assessment and monitoring of myocardial inflammation in MI.
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