Ultra-small superparamagnetic particles of iron oxide (USPIO) consist of an iron oxide core surrounded by a carbohydrate or polymer coating and are small enough to extravasate through diseased microvessels. Accumulation of USPIOs reduces T2* (or T2 star) decay time and creates signal deficits that can be quantified and visualized using T2* MRI. Thus, USPIO-enhanced MRI can detect tissue-resident macrophage activity and identify cellular inflammation within tissues. Development of a reliable, non-invasive imaging technique capable of directly detecting myocardial cellular inflammation could facilitate risk stratification and therapeutic targeting of macrophages immediately after myocardial infarction (MI). Furthermore, this technique could provide diagnostic information, serial disease monitoring, and a measure of treatment response in similar conditions.
For a study published in Heart, my colleagues and I report, for the first time, the successful imaging, quantification, and validation of cellular inflammation and myocardial edema over 3 months in patients following myocardial infarction using USPIO-enhanced cardiac MRI. This work establishes this technique as a way of exploring and monitoring myocardial cellular inflammation that could have wide-reaching implications and applications.
We recruited patients with acute MI and found USPIO enhancement in the infarct zone of the myocardium for up to 2 weeks. The time course of USPIO enhancement is in keeping with the known duration of macrophage infiltration following MI. Furthermore, we have provided critical histology data showing co-localization of USPIO with macrophages within the infarct zone of patients with recent MI. We also demonstrated that the time course of cellular inflammation after MI is distinct from the generalized tissue edema and loss of capillary integrity by comparing standard measure of edema with USPIO-enhanced T2 imaging.
Stirrat C, Alam S, MacGillivray T, et al. Ferumoxytol-enhanced magnetic resonance imaging assessing inflammation after myocardial infarction. Heart. 2017;103:1528-1535. Available at http://heart.bmj.com/content/103/19/1528.