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.

[1]  J. Gillard,et al.  Identifying Inflamed Carotid Plaques Using In Vivo USPIO-Enhanced MR Imaging to Label Plaque Macrophages , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[2]  P J Gallagher,et al.  Histological Assessment of 526 Symptomatic Carotid Plaques in Relation to the Nature and Timing of Ischemic Symptoms: The Oxford Plaque Study , 2006, Circulation.

[3]  V. Fuster,et al.  Characterization of Atherosclerotic Plaques by Magnetic Resonance Imaging , 2000, Annals of the New York Academy of Sciences.

[4]  Aaron J. Miller,et al.  The use of power images to perform quantitative analysis on low SNR MR images. , 1993, Magnetic resonance imaging.

[5]  Martin J Graves,et al.  In Vivo Detection of Macrophages in Human Carotid Atheroma: Temporal Dependence of Ultrasmall Superparamagnetic Particles of Iron Oxide–Enhanced MRI , 2004, Stroke.

[6]  Martin J Graves,et al.  The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. , 2009, Journal of the American College of Cardiology.

[7]  J. Gillard,et al.  Noninvasive imaging of carotid plaque inflammation , 2004, Neurology.

[8]  M. E. Kooi,et al.  Accumulation of Ultrasmall Superparamagnetic Particles of Iron Oxide in Human Atherosclerotic Plaques Can Be Detected by In Vivo Magnetic Resonance Imaging , 2003, Circulation.

[9]  E. Warburton,et al.  Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[10]  Z. Fayad,et al.  Iron oxide magnetic resonance imaging for atherosclerosis therapeutic evaluation: still "rusty?". , 2009, Journal of the American College of Cardiology.

[11]  A. Olukotun,et al.  Phase I clinical evaluation of a new iron oxide MR contrast agent , 1994, Journal of magnetic resonance imaging : JMRI.

[12]  J. Gillard,et al.  Utility of USPIO-enhanced MR imaging to identify inflammation and the fibrous cap: a comparison of symptomatic and asymptomatic individuals. , 2009, European journal of radiology.

[13]  E. Warburton,et al.  Correlation of Carotid Atheromatous Plaque Inflammation Using USPIO-Enhanced MR Imaging With Degree of Luminal Stenosis , 2008, Stroke.

[14]  Chun Yuan,et al.  T1‐insensitive flow suppression using quadruple inversion‐recovery , 2002, Magnetic resonance in medicine.

[15]  Martin J Graves,et al.  Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques contralateral to symptomatic carotid stenosis: an ultra small superparamagnetic iron oxide enhanced magnetic resonance study , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[16]  F. A. Seiler,et al.  Numerical Recipes in C: The Art of Scientific Computing , 1989 .

[17]  W. Kerwin,et al.  The vulnerable, or high-risk, atherosclerotic plaque: noninvasive MR imaging for characterization and assessment. , 2007, Radiology.

[18]  O. Baffa,et al.  MRI relaxometry: methods and applications , 2006 .

[19]  M. Wendland,et al.  T1 and T2 relaxivity of intracellular and extracellular USPIO at 1.5T and 3T clinical MR scanning , 2006, European Radiology.

[20]  Elena Bonanno,et al.  Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. , 2004, JAMA.

[21]  C. Gallagher.  Extending the Linear Model With R: Generalized Linear, Mixed Effects and Nonparametric Regression Models , 2007 .

[22]  C Yuan,et al.  Carotid atherosclerotic plaque: noninvasive MR characterization and identification of vulnerable lesions. , 2001, Radiology.