Ultrasmall Superparamagnetic Particles of Iron Oxide in Patients With Acute Myocardial Infarction

Abstract

Magnetic resonance imaging (MRI) is ideally suited for the serial examination of the heart because it is noninvasive, does not involve ionizing radiation, and has excellent soft tissue contrast and spatial resolution. Cardiac magnetic resonance, using T2-weighted imaging, has previously been used to detect Background-Inflammation following acute myocardial infarction (MI) has detrimental effects on reperfusion, myocardial remodelling, and ventricular function. Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide can detect cellular inflammation in tissues, and we therefore explored their role in acute MI in humans. Methods and Results-Sixteen patients with acute ST-segment elevation MI were recruited to undergo 3 sequential magnetic resonance scans within 5 days of admission at baseline, 24 and 48 hours following no infusion (controls; n=6) or intravenous infusion of ultrasmall superparamagnetic particles of iron oxide (n=10; 4 mg/kg). T2*-weighted multigradient-echo sequences were acquired and R2* values were calculated for specific regions of interest. In the control group, R2* values remained constant in all tissues across all scans with excellent repeatability (bias of −0.208 s Key Words: myocardial infarction ◼ inflammation ◼ magnetic resonance imaging ◼ ultrasmall superparamagnetic particles of iron oxide

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

“…23 Ferucarbotran and ferumoxides, approved for MRI in the past, were similarly withdrawn from the market. To fulfil the clinical need, the intravenous iron replacement agent ferumoxytol (Feraheme/Rienso, 17-30 nm particles coated with a low-molecular-weight semisynthetic carboxylated polymer) was used as a contrast agent to characterize the myocardial infarct pathology 24,25 and to differentiate simple steatosis from NASH. 26 It must be noted, however, that the required concentrations of ferumoxytol were very high, 4-7.2 mg Fe/kg body weight in myocardial infarct 24,25 and 3.6 mg/kg in patients with liver disease.…”

T 1 mapping for assessment of myocardial injury and microvascular obstruction at one week post myocardial infarction

“…Several oedema imaging methods exist-single-photon emission computed tomography, [26] T2W CMR, [19] LGE endocardial surface area, [27] T1 mapping CMR, [3,4,23] and T2 mapping CMR[13, 23]-but this study represents the first application of T1 mapping with a quantitative ROC-threshold optimised to a STEMI population. The precedent for such an approach was set by Ferreira et al [28], in a recent study on myocarditis.…”

“…Indeed, this hypothesis was put forward by other investigators who showed that ultra-small superparamagnetic particles of iron oxide are retained in segments very remote from the infarct. [27] Second, the T1 may have been abnormal in these patients prior to myocardial infarction, due to discrete microscopic fibrosis caused by comorbidities such as diabetes, hypertension or hypercholesterolemia. [30,31] In order to establish which hypothesis is correct, our findings would have to be validated through histology.…”

Remote magnetic targeting of iron oxide nanoparticles for cardiovascular diagnosis and therapeutic drug delivery: where are we now?

“…This characteristic was already shown in clinical trials for myocardial infarction, aortic aneurysms, and carotid plaques. 3,4,50,51 Furthermore, imaging of iron-laden leukocytes during pathologies such as atherosclerosis, stroke, and various types of cancer is a promising field of current preclinical research, as recently reviewed elsewhere. 20 IONs have a high sensitivity in MRI, as concentrations in the nanomolar range can be detected and visualized.…”