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on April 28, 2003

Circulation. 2003
Published online before print April 28, 2003, doi: 10.1161/01.CIR.0000068315.98705.CC
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Submitted on December 31, 2002
Accepted on February 25, 2003

Accumulation of Ultrasmall Superparamagnetic Particles of Iron Oxide in Human Atherosclerotic Plaques Can Be Detected by In Vivo Magnetic Resonance Imaging

M. E. Kooi PhD*, V. C. Cappendijk MD, K. B.J.M. Cleutjens PhD, A. G.H. Kessels MD, MSc, P. J.E.H.M. Kitslaar MD, PhD, M. Borgers PhD, P. M. Frederik PhD, M. J.A.P. Daemen MD, PhD, and J. M.A. van Engelshoven MD, PhD

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.

* To whom correspondence should be addressed. 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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