In vivo carotid plaque MRI using quantitative T₂* measurements with ultrasmall superparamagnetic iron oxide particles: a dose–response study to statin therapy

This study investigates T₂* 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 T₂*‐weighted sequence as well as quantitative T₂* (qT₂*) 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 T₂*‐weighted sequence demonstrated an initial increase (T₁ effect), followed by a decrease (T₂* effect), in relative signal intensity with increasing concentrations of USPIO. The qT₂* values decreased exponentially with increasing concentrations of USPIO. In the patient study, there was a highly significant difference in post‐USPIO T₂* measurements in plaques between the low‐ and high‐dose statin groups. This was observed for both the difference in qT₂* measurements (post‐USPIO minus pre‐USPIO) (p < 0.001) and for qT₂* post‐USPIO only (p < 0.001). The post‐USPIO qT₂* 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 qT₂* 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 © 2010 John Wiley & Sons, Ltd.