Published Online
on August 17, 2006

A more recent version of this article appeared on September 1, 2006

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Submitted on February 21, 2006
Revised on April 29, 2006
Accepted on May 15, 2006

Assessment of Inflammatory Burden Contralateral to the Symptomatic Carotid Stenosis Using High-Resolution Ultrasmall, Superparamagnetic Iron Oxide-Enhanced MRI

Tjun Tang MRCS; Simon P.S. Howarth MRCS; Sam R. Miller PhD; Rikin Trivedi MRCS; Martin J. Graves MSc; Jean U. King-Im MRCS; Zhi Y. Li PhD; Andrew P. Brown BSc; Peter J. Kirkpatrick FRCS; Michael E. Gaunt MD; and Jonathan H. Gillard MD^*

From the University Department of Radiology (T.T., S.P.S.H., R.T., M.J.G., J.U.K.-I., Z.Y.L., J.H.G.), Cambridge University Hospitals NHS Foundation Trust, Cambridge; Biostatistics and Data Sciences (S.R.M.), GlaxoSmithKline, Harlow; Translational Medicine and Genetics (A.P.B.), GlaxoSmithKline, Greenford; Department of Neurosurgery (S.P.S.H., P.K.), Cambridge University Hospitals NHS Foundation Trust, Cambridge; and the Vascular Unit (T.T., M.E.G.), Cambridge University Hospitals NHS Foundation Trust, Cambridge, England.

^* To whom correspondence should be addressed. E-mail: jhg21{at}cam.ac.uk.

Background and Purpose--It is well known that the vulnerable atheromatous plaque has a thin, fibrous cap and large lipid core with associated inflammation. This inflammation can be detected on MRI with use of a contrast medium, Sinerem, an ultrasmall superparamagnetic iron oxide (USPIO). Although the incidence of macrophage activity in asymptomatic disease appears low, we aimed to explore the incidence of MRI-defined inflammation in asymptomatic plaques in patients with known contralateral symptomatic disease.

Methods--Twenty symptomatic patients underwent multisequence MRI before and 36 hours after USPIO infusion. Images were manually segmented into quadrants, and the signal change in each quadrant was calculated after USPIO administration. A mixed mathematical model was developed to compare the mean signal change across all quadrants in the 2 groups. Patients had a mean symptomatic stenosis of 77% compared with 46% on their asymptomatic side, as measured by conventional angiography.

Results--There were 11 (55%) men, and the median age was 72 years (range, 53 to 84 years). All patients had risk factors consistent with severe atherosclerotic disease. All symptomatic carotid stenoses had inflammation, as evaluated by USPIO-enhanced imaging. On the contralateral sides, inflammatory activity was found in 19 (95%) patients. Contralaterally, there were 163 quadrants (57%) with a signal loss after USPIO when compared with 217 quadrants (71%) on the symptomatic side (P=0.007).

Conclusions--This study adds weight to the argument that atherosclerosis is a truly systemic disease. It suggests that investigation of the contralateral side in patients with symptomatic carotid stenosis can demonstrate inflammation in 95% of plaques, despite a mean stenosis of only 46%. Thus, inflammatory activity may be a significant risk factor in asymptomatic disease in patients who have known contralateral symptomatic disease. Patients with symptomatic carotid disease should have their contralateral carotid artery followed up.

Key words: atherosclerosis • carotid stenosis • contrast media • inflammation • magnetic resonance imaging • USPIO

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