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 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 qT(2)* post-USPIO only (p < 0.001). The post-USPIO qT(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.
Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. andrew.patterson@addenbrookes.nhs.uk
Andrew J
AJ
Patterson
Tjun Y
TY
Tang
Martin J
MJ
Graves
Karin H
KH
Müller
Jonathan H
JH
Gillard
D000368:Aged; D000069059:Atorvastatin; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology*; D003911:Dextrans; D004305:Dose-Response Relationship, Drug; D017352:Echo-Planar Imaging; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D019047:Phantoms, Imaging; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology
D003911:Dextrans; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D058185:Magnetite Nanoparticles; D011758:Pyrroles; C097921:ferumoxtran-10; D000069059:Atorvastatin