Evaluation of ultrasmall superparamagnetic iron-oxide (USPIO) enhanced MRI with ferumoxytol to quantify arterial wall inflammation.

BACKGROUND AND AIMS: Inflammation in atherosclerotic plaques is an important determinant of plaque vulnerability, and can be detected non-invasively using ultra-small superparamagnetic iron-oxide (USPIO) enhanced MRI. The aims of the current study were: 1) to determine whether ferumoxytol can be used for USPIO-MRI of atherosclerotic plaques, 2) to establish a protocol for quantitative USPIO-MRI of carotid artery plaques using ferumoxytol, and 3) to study the relation between USPIO uptake and plaque burden and 18 F-fluorodeoxyglucose (FDG) uptake (measured by 18 F-FDG PET/CT scan) in atherosclerotic plaques.

METHODS: In 9 patients with carotid artery stenosis >30% and 4 healthy controls, quantitative R2* MRI scans of the carotid arteries were performed before and 72 h after USPIO administration (4 mg/kg ferumoxytol). USPIO uptake was assessed by quantifying the difference in R2* (ΔR2*) between baseline and post-USPIO scans. In addition to MRI, 18 F-FDG PET/CT was performed on both carotid arteries. MR and PET/CT images were co-registered, and 18 F-FDG uptake was quantified in all slices containing atherosclerotic plaque.

RESULTS: Infusion of ferumoxytol resulted in higher R2* values after 72 h in atherosclerotic plaques (ΔR2* 24.6 ± 19.8 s-1 ; p = 0.0003), but not in the healthy control vessel wall (ΔR2* 2.6 ± 5.6 s-1 , p = 0.23). USPIO uptake in patients was higher in atherosclerotic plaques compared to the patient non-plaque vessel wall (ΔR2* of 24.6 ± 19.8 vs. 7.5 ± 9.3 s-1 , p = 0.004). No correlation was found between USPIO uptake and 18 F-FDG uptake in atherosclerotic plaques (R2  = 0.03, p = 0.55).

CONCLUSIONS: Ferumoxytol is selectively taken up by atherosclerotic plaques and can thus be used for carotid USPIO-MRI. As USPIO and 18 F-FDG uptake in atherosclerotic plaque do not correlate in this cohort, these agents may visualize different pathophysiological aspects of plaque inflammation.