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 F-18-fluorodeoxyglucose (FDG) uptake (measured by F-18-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* (DR2*) between baseline and post-USPIO scans. In addition to MRI, F-18-FDG PET/CT was performed on both carotid arteries. MR and PET/CT images were co-registered, and F-18-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 (DR2* 24.6 +/- 19.8 s(-1); p = 0.0003), but not in the healthy control vessel wall (DR2* 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 (DR2* of 24.6 +/- 19.8 vs. 7.5 +/- 9.3 s(-1), p = 0.004). No correlation was found between USPIO uptake and F-18-FDG uptake in atherosclerotic plaques (R-2 = 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 F-18-FDG uptake in atherosclerotic plaque do not correlate in this cohort, these agents may visualize different pathophysiological aspects of plaque inflammation. (C) 2017 Elsevier B.V. All rights reserved