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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    • "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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    BioMed Research International 01/2015; 2015:914516. DOI:10.1155/2015/914516 · 2.71 Impact Factor
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    • "There is a wide range of molecular imaging modalities employed for detection and characterization of atherosclerosis, primarily in large vessels. Examples include positron emission tomography (PET) with 18F-FDG [5], magnetic resonance imaging (MRI) using ultra-small super-paramagnetic iron oxide (USPIO) probes [6], [7], single photon emission computed tomography (SPECT) using VCAM-1-specific 99mTc-labeled peptidic sequences [8], and the iodinated nanoparticulate contrast agent N1177 for computed tomography (CT) [9]. However, application of these external imaging approaches to coronary atherosclerosis has been challenging due to small coronary size, cardiac motion, and detecting adequate signal and contrast. "
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    PLoS ONE 09/2014; 9(9):e108108. DOI:10.1371/journal.pone.0108108 · 3.23 Impact Factor
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    • "The availability of PET/MRI systems may dramatically facilitate the translation of promising PET imaging into the clinic for atherosclerotic plaque imaging owing to the superior soft tissue contrast of MRI imaging.[91],[92] Millon, et al.[93] in their recent experimental study showed the feasibility of using combined PET/MRI for assessment of changes in the inflammation of atherosclerotic plaques. "
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