Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, UK-I JM, 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. J Am Coll Cardiol. 2009;53(22):2039-50

University Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Journal of the American College of Cardiology (Impact Factor: 16.5). 06/2009; 53(22):2039-50. DOI: 10.1016/j.jacc.2009.03.018
Source: PubMed


The aim of this study was to evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). The hypothesis was that treatment with 80 mg atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI-defined inflammation within the first 3 months of therapy.
Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of plaque inflammation.
Forty-seven patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomly assigned in a balanced, double-blind manner to either 10 or 80 mg atorvastatin daily for 12 weeks. Baseline statin therapy was equivalent to 10 mg of atorvastatin or less. The primary end point was change from baseline in signal intensity (DeltaSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks.
Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (DeltaSI 0.13; p = 0.0003) and at 12 weeks (DeltaSI 0.20; p < 0.0001). No difference was observed with the low-dose regimen. The 80-mg atorvastatin dose significantly reduced total cholesterol by 15% (p = 0.0003) and low-density lipoprotein cholesterol by 29% (p = 0.0001) at 12 weeks.
Aggressive lipid-lowering therapy over a 3-month period is associated with significant reduction in USPIO-defined inflammation. USPIO-enhanced MRI methodology may be a useful imaging biomarker for the screening and assessment of therapeutic response to "anti-inflammatory" interventions in patients with atherosclerotic lesions. (Effects of Atorvastatin on Macrophage Activity and Plaque Inflammation Using Magnetic Resonance Imaging [ATHEROMA]; NCT00368589).

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Available from: Martin John Graves, Mar 29, 2014
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    • "Although residual stress is rarely considered in the majority of in vivo imaging-based computation modelling studies, neglecting this force may lead to an overestimation of FC stress and stretch concentrations (Ohayon et al., 2007). Secondly, the ultimate strength has a close association with local inflammation, which may be quantifiable through ultrasmall superparamagnetic iron oxide-enhanced (USPIO) MR imaging (Tang et al., 2009) or positron emission tomography with 2-deoxy- 2-[fluorine-18]fluoro-D-glucose integrated with computed tomography ( 18 F-FDG-PET/CT) imaging (Tarkin et al., 2014). Lower strength thresholds should be adopted for mechanical-based vulnerability assessment if heavy inflammation is present within plaques. "
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    • "In the latter studies, a strong accumulation of USPIO (ferumoxytol, Rienso) in the infarct tissue allowed a better characterization of the injured myocardium and inflammatory macrophage accumulation, as well as the extent and composition of the peri-infarct zone, as compared with Magnevist ® [40]. Apart from providing prognostic information and aiding disease diagnosis, SPION/USPIO can constitute a useful tool both for monitoring the treatment efficacy [29] and for the assessment of future event risk in asymptomatic patients with carotid atherosclerosis [10]. Moreover, SPION-labeling enables visualization of the cells in vivo for the purpose of monitoring of cell therapies and tracking inflammatory cells by MRI [24]). "
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    • "Clinical studies have demonstrated uptake of small iron oxide (USPIO) particles in carotid plaques and the uptake was found to correspond to areas of macrophage infiltration [13]. One study has even used USPIO-enhanced carotid MRI to assess the therapeutic response of short term aggressive lipid lower therapy [14]. Fibrin is another molecular target of MRI utilizing a fibrinspecific gadolinium-based contrast agent. "
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