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

Abstract

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.

• Authors: Andrew J Patterson, Tjun Y Tang, Martin J Graves, Karin H Müller, Jonathan H Gillard
• Journal: NMR in biomedicine (NMR Biomed) Vol. 24 Issue 1 Pg. 89-95 (Jan 2011) ISSN: 1099-1492 [Electronic] England
• PMID: 21259368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 John Wiley & Sons, Ltd.

Chemical References

• Dextrans
• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Magnetite Nanoparticles
• Pyrroles
• ferumoxtran-10
• Atorvastatin

Topics

• Aged
• Atorvastatin
• Carotid Arteries (drug effects, pathology)
• Dextrans
• Dose-Response Relationship, Drug
• Echo-Planar Imaging
• Female
• Heptanoic Acids (administration & dosage, pharmacology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, pharmacology)
• Magnetic Resonance Angiography (methods)
• Magnetite Nanoparticles
• Male
• Phantoms, Imaging
• Pyrroles (administration & dosage, pharmacology)