This Article Full Text Full Text (PDF) All Versions of this Article: 35/7/1631    most recent 01.STR.0000131268.50418.b7v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Trivedi, R. A. Articles by Gillard, J. H. Search for Related Content PubMed PubMed Citation Articles by Trivedi, R. A. Articles by Gillard, J. H. Related Collections Other arteriosclerosis Imaging Carotid Stenosis Computerized tomography and Magnetic Resonance Imaging

(Stroke. 2004;35:1631.)
© 2004 American Heart Association, Inc.

Original Contributions

In Vivo Detection of Macrophages in Human Carotid Atheroma

Temporal Dependence of Ultrasmall Superparamagnetic Particles of Iron Oxide-Enhanced MRI

Rikin A. Trivedi, MRCS; Jean-Marie U-King-Im, MRCS; Martin J. Graves, MSc; Justin J. Cross, FRCR; Jo Horsley, MSc; Martin J. Goddard, MRCPath; Jeremy N. Skepper, PhD; George Quartey, PhD; Elizabeth Warburton, MRCP; Ilse Joubert; Liqun Wang, PhD; Peter J. Kirkpatrick, FRCS(SN); John Brown, FMedSci Jonathan H. Gillard, FRCR

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

Correspondence to Dr Jonathan H. Gillard, University Department of Radiology, Addenbrooke’s Hospital, Box 219, Hills Road, Cambridge CB22QQ, UK. E-mail jhg21{at}cam.ac.uk

Background— It has been suggested that inflammatory cells within vulnerable plaques may be visualized by superparamagnetic iron oxide particle-enhanced MRI. The purpose of this study was to determine the time course for macrophage visualization with in vivo contrast-enhanced MRI using an ultrasmall superparamagnetic iron oxide (USPIO) agent in symptomatic human carotid disease.

Methods— Eight patients scheduled for carotid endarterectomy underwent multisequence MRI of the carotid bifurcation before and 24, 36, 48, and 72 hours after Sinerem (2.6 mg/kg) infusion.

Results— USPIO particles accumulated in macrophages in 7 of 8 patients given Sinerem. Areas of signal intensity reduction, corresponding to USPIO/macrophage-positive histological sections, were visualized in all 7 of these patients, optimally between 24 and 36 hours, decreasing after 48 hours, but still evident up to 96 hours after infusion.

Conclusions— USPIO-enhanced MRI of carotid atheroma can be used to identify macrophages in vivo. The temporal change in the resultant signal intensity reduction on MRI suggests an optimal time window for the detection of macrophages on postinfusion imaging.

Key Words: magnetic resonance imaging • carotid arteries • atherosclerosis • macrophages

This article has been cited by other articles:

				T. Y Tang, S. P S Howarth, S. R Miller, M. J Graves, J.-M. U-King-Im, R. A Trivedi, Z. Y. Li, S. R Walsh, A. P Brown, P. J Kirkpatrick, et al. Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques contralateral to symptomatic carotid stenosis: an ultra small superparamagnetic iron oxide enhanced magnetic resonance study J. Neurol. Neurosurg. Psychiatry, December 1, 2007; 78(12): 1337 - 1343. [Abstract] [Full Text] [PDF]

				F. A. Jaffer, P. Libby, and R. Weissleder Molecular Imaging of Cardiovascular Disease Circulation, August 28, 2007; 116(9): 1052 - 1061. [Full Text] [PDF]

				D. E. Sosnovik, M. Nahrendorf, and R. Weissleder Molecular Magnetic Resonance Imaging in Cardiovascular Medicine Circulation, April 17, 2007; 115(15): 2076 - 2086. [Full Text] [PDF]

				T. Tang, S. P.S. Howarth, S. R. Miller, R. Trivedi, M. J. Graves, J. U. King-Im, Z. Y. Li, A. P. Brown, P. J. Kirkpatrick, M. E. Gaunt, et al. Assessment of Inflammatory Burden Contralateral to the Symptomatic Carotid Stenosis Using High-Resolution Ultrasmall, Superparamagnetic Iron Oxide-Enhanced MRI Stroke, September 1, 2006; 37(9): 2266 - 2270. [Abstract] [Full Text] [PDF]

				J. R. Crouse III Thematic review series: Patient-Oriented Research. Imaging atherosclerosis: state of the art J. Lipid Res., August 1, 2006; 47(8): 1677 - 1699. [Abstract] [Full Text] [PDF]

				F. Cengelli, D. Maysinger, F. Tschudi-Monnet, X. Montet, C. Corot, A. Petri-Fink, H. Hofmann, and L. Juillerat-Jeanneret Interaction of Functionalized Superparamagnetic Iron Oxide Nanoparticles with Brain Structures J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 108 - 116. [Abstract] [Full Text] [PDF]

				R. A. Trivedi, C. Mallawarachi, J.-M. U-King-Im, M. J. Graves, J. Horsley, M. J. Goddard, A. Brown, L. Wang, P. J. Kirkpatrick, J. Brown, et al. Identifying Inflamed Carotid Plaques Using In Vivo USPIO-Enhanced MR Imaging to Label Plaque Macrophages Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1601 - 1606. [Abstract] [Full Text] [PDF]

				G. Stoll and M. Bendszus Inflammation and Atherosclerosis: Novel Insights Into Plaque Formation and Destabilization Stroke, July 1, 2006; 37(7): 1923 - 1932. [Abstract] [Full Text] [PDF]

				F. A. Jaffer, P. Libby, and R. Weissleder Molecular and Cellular Imaging of Atherosclerosis: Emerging Applications J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1328 - 1338. [Abstract] [Full Text] [PDF]

				S. A. Wickline, A. M. Neubauer, P. Winter, S. Caruthers, and G. Lanza Applications of Nanotechnology to Atherosclerosis, Thrombosis, and Vascular Biology Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 435 - 441. [Abstract] [Full Text] [PDF]

				F. Hyafil, J.-P. Laissy, M. Mazighi, D. Tchetche, L. Louedec, H. Adle-Biassette, S. Chillon, D. Henin, M.-P. Jacob, D. Letourneur, et al. Ferumoxtran-10-Enhanced MRI of the Hypercholesterolemic Rabbit Aorta: Relationship Between Signal Loss and Macrophage Infiltration Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 176 - 181. [Abstract] [Full Text] [PDF]

				N. Nighoghossian, L. Derex, and P. Douek The Vulnerable Carotid Artery Plaque: Current Imaging Methods and New Perspectives Stroke, December 1, 2005; 36(12): 2764 - 2772. [Abstract] [Full Text] [PDF]

				J.K. Lovett, J.N.E. Redgrave, and P.M. Rothwell A Critical Appraisal of the Performance, Reporting, and Interpretation of Studies Comparing Carotid Plaque Imaging With Histology Stroke, May 1, 2005; 36(5): 1085 - 1091. [Abstract] [Full Text] [PDF]

				F. A. Jaffer and R. Weissleder Molecular Imaging in the Clinical Arena JAMA, February 16, 2005; 293(7): 855 - 862. [Abstract] [Full Text] [PDF]

				J.-C. Baron and S. Warach Imaging Stroke, February 1, 2005; 36(2): 196 - 199. [Full Text] [PDF]