Circulation. 2003;107:2453-2458
Published online before print April 28, 2003, doi: 10.1161/01.CIR.0000068315.98705.CC
Published online before print April 28, 2003, doi: 10.1161/01.CIR.0000068315.98705.CC
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(Circulation. 2003;107:2453.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Accumulation of Ultrasmall Superparamagnetic Particles of Iron Oxide in Human Atherosclerotic Plaques Can Be Detected by In Vivo Magnetic Resonance Imaging
From the Cardiovascular Research Institute Maastricht (CARIM), Departments of Radiology (M.E.K., V.C.C., J.M.A.v.E.), Pathology (K.B.J.M.C., P.M.F., M.J.A.P.D.), Clinical Epidemiology and Medical Technology Assessment (A.G.H.K.), Surgery (P.J.E.H.M.K.), and Genetics and Cell Biology (M.B.), University Hospital Maastricht/University of Maastricht, the Netherlands.
Correspondence to Dr M.E. Kooi, Department of Radiology, University Hospital Maastricht, Peter Debyelaan 25, 6229 HX Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail ekoo{at}rdia.azm.nl
Background— One of the features of high-risk atherosclerotic plaques is a preponderance of macrophages. Experimental studies with hyperlipidemic rabbits have shown that ultrasmall superparamagnetic particles of iron oxide (USPIOs) accumulate in plaques with a high macrophage content and that this induces magnetic resonance (MR) signal changes. The purpose of our study was to investigate whether USPIO-enhanced MRI can also be used for in vivo detection of macrophages in human plaques.
Methods and Results— MRI was performed on 11 symptomatic patients scheduled for carotid endarterectomy before and 24 (n=11) and 72 (n=5) hours after administration of USPIOs (Sinerem) at a dose of 2.6 mg Fe/kg. Histological and electron microscopical analyses of the plaques showed USPIOs primarily in macrophages within the plaques in 10 of 11 patients. Histological analysis showed USPIOs in 27 of 36 (75%) of the ruptured and rupture-prone lesions and 1 of 14 (7%) of the stable lesions. Of the patients with USPIO uptake, signal changes in the post-USPIO MRI were observed by 2 observers in the vessel wall in 67 of 123 (54%) and 19 of 55 (35%) quadrants of the T2*-weighted MR images acquired after 24 and 72 hours, respectively. For those quadrants with changes, there was a significant signal decrease of 24% (95% CI, 33% to 15%) in regions of interest in the images acquired after 24 hours, whereas no significant signal change was found after 72 hours.
Conclusions— Accumulation of USPIOs in macrophages in predominantly ruptured and rupture-prone human atherosclerotic lesions caused signal decreases in the in vivo MR images.
Key Words: atherosclerosis • magnetic resonance imaging • plaque • contrast media • carotid arteries
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|
|
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|
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|
|
|
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|
|
|
|
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|
|
|
|
|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
S. Warach and J.-C. Baron Neuroimaging Stroke, February 1, 2004; 35(2): 351 - 353. [Full Text] [PDF]
|
|
|
|
|
|
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|
|