912Nanoparticle Enhanced CMR – A Novel Method Of Investigating Myocardial Inflammation & Dysfunction

Abstract

Purpose: Myocardial inflammation following infarction or coronary bypass graft (CABG) surgery exerts detrimental effects on ventricular remodelling and function. “Ultrasmall superparamagnetic particles of iron-oxide” (USPIOs) are internalised by inflammatory cells, and shorten T2* decay times during magnetic resonance imaging (MRI). The aim of the study was to assess whether USPIOs could be used to measure in vivo myocardial cellular inflammation after ST-elevation myocardial infarction (STEMI) or CABG surgery. Methods: Patients underwent MRI 2-4 days post STEMI (baseline), and 24-hours after intravenous USPIO infusion (4 mg/kg Ferumoxytol; n = 10) or no infusion (n = 6). The same protocol was performed in 47 patients 5-28 days following on-pump CABG and 10 healthy volunteers, with all subjects receiving USPIO. Standard Cardiac MRI was performed at 3T. USPIO imaging was performed using T2*-weighted multi-gradient-echo sequences. Four echoes (TE = 2.13, 4.27, 6.41, 8.55 ms) were combined to create R2* (1/T2*) maps, that were used to evaluate USPIO uptake (Figure 1). Plasma troponin I concentrations were determined by high sensitivity assay in patients undergoing CABG surgery. Results (Figure 2): Following USPIO administration, R2* values increased in the liver and spleen consistent with uptake by the reticuloendothelial system. In patients with STEMI, there was a large increase in R2* in infarcted myocardium (41 ± 12 to 155 ± 45 s−1; p<0.001) indicative of macrophage accumulation in this region. There was only a small increase in R2* in the myocardium remote from the infarct (39 ± 3 to 80 ± 15 s−1; p<0.001), similar to the increase observed in the myocardium of healthy volunteers (44 ± 6 to 88 ± 12 s−1). This represented USPIO laden blood pooling. In contrast, R2* signal increased further in the myocardium of CABG surgery patients (44 ± 6 to 114 ± 21 s−1; p<0001) and this was greater than in the myocardium of healthy volunteers (p<0.05), but lower than the infarcted myocardium (p<0.001). High sensitivity troponin I increased 1340 fold from baseline (8 ± 9 pg/ml) to a peak at 6 hours (4809 ± 6176 pg/ml), and correlated with R2* increase (r = 0.34, p = 0.03). R2* map Results