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

NMR Biomed. 2011 Jan;24(1):89-95. doi: 10.1002/nbm.1560. Epub 2010 Dec 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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