Currently, characterization of the vulnerable plaque is a hot research topic as a more adequate strategy for preventing cerebrovascular events is being sought. Histological studies have recognized that plaque inflammation and the presence of adventitial vasa vasorum, intimal angiogenesis and plaque neovascularization are strong predictors of instability in atheromatous lesions of cerebrovascular and cardiovascular patients. The in vivo study of these features has been the focus of development of several new radiological imaging methods. Carotid ultrasound, with ultrasound contrast agents, is not only able to provide an enhanced assessment of the arterial lumen and plaque morphology with an improved resolution of the carotid intima-media thickness, but also to directly visualize adventitial vasa vasorum and plaque neovascularization. This technique and its future clinical implications are discussed in the present review.

Keywords:
Carotid plaque vascularization, Adventitial vasa vasorum, Carotid ultrasound, Echo contrast agents
1.
Hennerici MG: The unstable plaque. Cerebrovasc Dis 2004;17(suppl 3):17–22.
2.
Rothwell PM, Eliasziw M, Gutnikov SA, Fox AJ, Taylor DW, Mayberg MR, Warlow CP, Barnett HJ, Carotid Endarterectomy Trialists’ Collaboration: Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 2003;361:107–116.
3.
Lenzi GL, Vicenzini E: The ruler is dead. An analysis of carotid plaque motion. Cerebrovasc Dis 2007;23:121–125.
4.
Bartels E: Color-Coded Duplex Ultrasound of the Cerebral Vessels. Atlas and Manual. Stuttgart, Schattauer, 1999.
5.
Ratliff DA, Gallagher PJ, Hames TK, Humphries KN, Webster JH, Chant AD: Characterisation of carotid artery disease: comparison of duplex scanning with histology. Ultrasound Med Biol 1985;11:835–840.
6.
Gray-Weale AC, Graham JC, Burnett JR, Byrne K, Lusby RJ: Carotid artery atheroma: comparison of preoperative B-mode ultrasound appearance with carotid endarterectomy specimen pathology. J Cardiovasc Surg 1988;29:676–681.
7.
Widder B, Paulat K, Hackspacher J, Hamann H, Hutschenreiter S, Kreutzer C, Ott F, Vollmar J: Morphological characterization of carotid artery stenoses by ultrasound duplex scanning. Ultrasound Med Biol 1990;16:349–354.
8.
Biasi GM, Sampaolo A, Mingazzini P, De Amicis P, El-Barghouty N, Nicolaides AN: Computer analysis of ultrasonic plaque echolucency in identifying high risk carotid bifurcation lesions. Eur J Vasc Endovasc Surg 1999;17:476–479.
9.
El-Barghouty N, Gerulakos G, Nicolaides AN, Androulakos A, Bahn V: Computer assisted carotid plaque characterization. Eur J Vasc Endov Surg 1995;9:389–393.
10.
Spagnoli LG, Mauriello A, Sangiorgi G: Extracranial thrombotically active carotid plaque as a risk factor of ischemic stroke. JAMA 2004;292:1845–1852.
11.
Beeuwkes R, Barger C, Silverman K, Lainery LL: Cinemicrographic studies of the vasa vasorum of the human coronary arteries; in Glagov S, Newman WP, Schaffer S (eds): Pathobiology of the Human Atherosclerotic Plaque. Springer, New York, 1990, pp 425–432.
12.
Clagett GP, Robinowitz M, Youkey JR, Fisher DF Jr, Fry RE, Myers SI, Lee EL, Collins GJ Jr, Virmani R: Morphogenesis and clinicopathologic characteristics of recurrent carotid disease. J Vasc Surg 1986;3:10–23.
13.
Fryer JA, Myers PC, Appleberg M: Carotid intraplaque hemorrhage: the significance of neovascularity. J Vasc Surg 1987;6:341–349.
14.
Kumamoto M, Nakashima Y, Sueishi K: Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance. Hum Pathol 1995;26:450–456.
15.
Mofidi R, Crotty TB, McCarthy P, Sheehan SJ, Mehigan D, Keaveny TV: Association between plaque instability, angiogenesis and symptomatic carotid occlusive disease. Br J Surg 2001;88:945–950.
16.
Fleiner M, Kummer M, Mirlacher M, Sauter G, Cathomas G, Krapf R, Biedermann BC: Arterial neovascularization and inflammation in vulnerable patients: early and late signs of symptomatic atherosclerosis. Circulation 2004;110:2843–2850.
17.
Moreno PR, Fuster V: New aspects in the pathogenesis of diabetic atherothrombosis. J Am Coll Cardiol 2004;44:2293–2300.
18.
Barger AC, Beeuwkes R, Lainey LL, Silverman KJ: Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. NEJM 1984;310:175–177.
19.
Dunmore BJ, McCarthy MJ, Naylor AR, Brindle NP: Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques. J Vasc Surg 2007;45:155–159.
20.
Warburton L, Gillard J: Functional imaging of carotid atheromatous plaques. J Neuroimaging 2006;16:293–301.
21.
Feinstein SB: The powerful microbubble: from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond. Am J Physiol Heart Circ Physiol 2004;287:450–457.
22.
Feinstein SB: Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol 2006;48:236–243.
23.
Vicenzini E, Giannoni MF, Puccinelli F, Ricciardi MC, Altieri M, Di Piero V, Gossetti B, Benedetti-Valentini F, Lenzi GL: Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke 2007;38:2841–2843.
24.
Shah F, Balan P, Weinberg M, Reddy V, Neems R, Feinstein M, Dainauskas J, Meyer P, Goldin M, Feinstein SB: Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vasc Med 2007;12:291–297.
25.
Purushothaman KR, Sanz J, Zias E, Fuster V, Moreno PR: Atherosclerosis neovascularization and imaging. Curr Mol Med 2006;6:549–556.
26.
Huang PT, Huang FG, Zou CP, Sun HY, Tian XQ, Yang Y, Tang JF, Yang PL, Wang XT: Contrast-enhanced sonographic characteristics of neovascularization in carotid atherosclerotic plaques. J Clin Ultrasound 2008;36:346–351.
27.
Denzel C, Fellner F, Wutke R, Bazler K, Muller KM, Lang W: Ultrasonographic analysis of arteriosclerotic plaques in the internal carotid artery. Eur J Ultrasound 2003;16:161–167.
28.
European Carotid Surgery Trialists’ Collaborative Group: Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379–1387.
29.
Sabeti S, Schillinger M, Mlekusch W, Willfort A, Haumer M, Nachtmann T, Mullner M, Lang W, Ahmadi R, Minar E: Quantification of internal carotid artery stenosis with duplex US: comparative analysis of different flow velocity criteria. Radiology 2004;232:431–439.
30.
Paterson JC: Capillary rupture with intimal haemorrhage as the causative factor in coronary thrombosis. Arch Pathol 1938;25:474–487.
31.
Geiringer E: Intimal vascularisation and atherosclerosis. Histologic characteristics of carotid atherosclerotid plaque. J Pathol Bacteriol 1951;63:201–211.
32.
Executive Committee for the Asymptomatic Carotid Atherosclerosis Study: Endarterectomy for asymptomatic carotid artery stenosis. JAMA 1995;273:1421–1428.
33.
Carlier S, Kakadiaris IA, Dib N, Vavuranakis M, O’Malley SM, Gul K, Hartley CJ, Metcalfe R, Mehran R, Stefanadis C, Falk E, Stone G, Leon M, Naghavi M: Vasa vasorum imaging: a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep 2005;7:164–169.
34.
McCarthy MJ, Loftus IM, Thompson MM, Jones L, London NJ, Bell PR, Naylor AR, Brindle NP: Angiogenesis and the atherosclerotic carotid plaque: an association between symptomatology and plaque morphology. J Vasc Surg 1999;30:261–268.
35.
Kumamoto M, Nakashima Y, Sueishi K: Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance. Hum Pathol 1995;26:450–456.
36.
Milei J, Parodi JC, Alonso GF, Barone A, Grana D, Matturri L: Carotid rupture and intraplaque hemorrhage: immunophenotype and role of cells involved. Am Heart J 1998;136:1096–1105.
37.
Bornstein NM, Krajewski A, Lewis AJ, Norris JW: Clinical significance of carotid plaque hemorrhage. Arch Neurol 1990;47:958–959.
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.