In vivo carotid plaque MRI using quantitative T-2* measurements with ultrasmall superparamagnetic iron oxide particles: a dose-response study to statin therapy

This study investigates T-2* quantification in carotid plaques before and after the administration of ultrasmall superparamagnetic iron oxide particles (USPIOs) in a cohort of patients receiving statin therapy. Phantom studies were performed using gels with varying concentrations of USPIOs. In the phantom study, 12 gels were prepared with a range of freely distributed concentrations of USPIO nanoparticles (0-0.05 mg/mL). Relative signal intensity measurements were obtained from a T-2*-weighted sequence as well as quantitative T-2* (qT(2)*) measurements. In the patient study, 40 patients with >40% carotid stenosis were randomised to low- and high-dose statin therapy (10 and 80 mg of atorvastatin). Pre- and post- (36 h) USPIO-enhanced MRI were performed at baseline, and at 6 and 12 weeks. A linear mixed-effects model was applied to account for the inherent correlation of multiple-plaque measurements from the same patient and to assess dose-response differences to statin therapy. In the phantom study, the T-2*-weighted sequence demonstrated an initial increase (T-1 effect), followed by a decrease (T-2* effect), in relative signal intensity with increasing concentrations of USPIO. The qT(2)* values decreased exponentially with increasing concentrations of USPIO. In the patient study, there was a highly significant difference in post-USPIO T-2* measurements in plaques between the low- and high-dose statin groups. This was observed for both the difference in qT(2)* measurements (post-USPIO minus pre-USPIO) (p <0.001) and for q T-2* post-USPIO only (p <0.001). The post-USPIO q T-2* values were as follows: baseline: low dose, 13.6 +/- 5.5 ms; high dose, 12.9 +/- 6.2 ms; 6 weeks: low dose, 13.3 +/- 6.7 ms; high dose, 14.3 +/- 7.7 ms; 12 weeks: low dose, 14.0 +/- 7.6 ms; high dose, 18.3 +/- 11.2 ms. It can be concluded that qT(2)* measurements provide an alternative method of quantifying USPIO uptake. These results also demonstrate that changes in USPIO uptake can be measured using post-USPIO imaging only. Copyright (C) 2010 John Wiley & Sons, Ltd.