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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1601.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Identifying Inflamed Carotid Plaques Using In Vivo USPIO-Enhanced MR Imaging to Label Plaque Macrophages

Rikin A. Trivedi; Chinthake Mallawarachi; Jean-Marie U-King-Im; Martin J. Graves; Jo Horsley; Martin J. Goddard; Andrew Brown; Liqun Wang; Peter J. Kirkpatrick; John Brown; Jonathan H. Gillard

From the University Department of Radiology (R.A.T., C.M., J.-M.U., M.J.G., J.H.G.), Addenbrooke’s Hospital, Cambridge, UK; the Department of Pathology (J.H., M.J.G.), Papworth Hospital, Cambridge, UK; GlaxoSmithKline (A.B., L.W., J.B.), Translational Medicine and Technology, Addenbrooke’s Centre for Clinical Investigation, Addenbrooke’s Hospital, Cambridge, UK; and the Academic Department of Neurosurgery (R.A.T., P.J.K.), Addenbrooke’s Hospital, Cambridge, UK.

Correspondence to Dr Trivedi, University Department of Radiology, Addenbrooke’s Hospital, Cambridge, UK. E-mail rt256{at}radiol.cam.ac.uk

Background— Inflammation within atherosclerotic lesions contributes to plaque instability and vulnerability to rupture. We set out to evaluate the use of a macrophage labeling agent to identify carotid plaque inflammation by in vivo magnetic resonance imaging (MRI).

Methods and Results— Thirty patients with symptomatic severe carotid stenosis scheduled for carotid endarterectomy underwent multi-sequence MRI of the carotid bifurcation before and after injection of ultrasmall superparamagnetic particles of iron oxide (USPIOs). USPIO particles accumulated in macrophages in 24 of 30 plaques (80%). Areas of signal intensity reduction, corresponding to USPIO/macrophage-positive histological sections, were visualized in 24 of 27 (89%) patients, with an average reduction in signal intensity induced by the USPIO particles of 24% (range, 3.1% to 60.8%).

Conclusions— USPIO-enhanced MRI can identify plaque inflammation in vivo by accumulation of USPIO within macrophages in carotid plaques.

The in vivo detection of plaque inflammation was evaluated using a macrophage labeling MRI contrast agent. Areas of focal signal loss on MRI corresponded to macrophage populations, thereby identifying inflamed plaques in 24 of 27 symptomatic individuals with severe ICA stenosis were detected and confirmed histologically.

Key Words: carotid • inflammation • MRI • USPIO • vulnerable plaque

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