Current Atherosclerosis Reports

, Volume 7, Issue 2, pp 164–169

Vasa vasorum imaging: A new window to the clinical detection of vulnerable atherosclerotic plaques

  • Stéphane Carlier
  • Ioannis A. Kakadiaris
  • Nabil Dib
  • Manolis Vavuranakis
  • Sean M. O’Malley
  • Khawar Gul
  • Craig J. Hartley
  • Ralph Metcalfe
  • Roxana Mehran
  • Christodoulos Stefanadis
  • Erling Falk
  • Gregg Stone
  • Martin Leon
  • Morteza Naghavi


Complications of vulnerable atherosclerotic plaques (rupture, luminal and mural thrombosis, intraplaque hemorrhage, rapid progression to stenosis, spasm, and so forth) lead to heart attacks and strokes. It remains difficult to identify what plaques are vulnerable to these complications. Despite recent developments such as thermography, spectroscopy, and magnetic resonance imaging, none of them is approved for clinical use. Intravascular ultrasound (IVUS), a relatively old yet widely available clinical tool for guiding intracoronary procedures, is increasingly used for characterization of atherosclerotic plaques. However, inability of IVUS in measuring plaque activity limits its value in detection of vulnerable plaques. In this review, we present new information suggesting that microbubble contrast-enhanced IVUS can measure activity and inflammation within atherosclerotic plaques by imaging vasa vasorum density. An increasing body of evidence indicates that vasa vasorum density may be a strong marker for plaque vulnerability. We suggest that a combination of structural assessment (cap thickness, lipid core, calcification, etc) and vasa vasorum density imaging by IVUS can serve as the most powerful clinically available tool for characterization of vulnerable plaques. Due to space limitations, all IVUS images and movies are posted on the website of the Ultimate IVUS Collaborative Project:


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Naghavi M, Libby P, Falk E, et al.: From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 2003, 108:1664–1672.PubMedCrossRefGoogle Scholar
  2. 2.
    Naghavi M, Libby P, Falk E, et al.: From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003, 108:1772–1778.PubMedCrossRefGoogle Scholar
  3. 3.
    Carlier SG, De Korte CL, Brusseau E, et al.: Elastography. J Cardiovasc Risk 2002, 9:237–245.PubMedCrossRefGoogle Scholar
  4. 4.
    Nair A, Kuban BD, Tuzcu EM, et al.: Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation 2002, 106:2200–2206.PubMedCrossRefGoogle Scholar
  5. 5.
    Kawasaki M, Takatsu H, Noda T, et al.: In vivo quantitative tissue characterization of human coronary arterial plaques by use of integrated backscatter intravascular ultrasound and comparison with angioscopic findings. Circulation 2002, 105:2487–2492.PubMedCrossRefGoogle Scholar
  6. 6.
    Barger AC, Beeuwkes R 3rd, Lainey LL, Silverman KJ: Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N Engl J Med 1984, 310:175–177.PubMedCrossRefGoogle Scholar
  7. 7.
    Moulton KS, Vakili K, Zurakowski D, et al.: Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci 2003, 8:4736–4741.CrossRefGoogle Scholar
  8. 8.
    Moreno PR, Purushothaman KR, Fuster V, O’Connor WN: Intimomedial interface damage and adventitial inflammation is increased beneath disrupted atherosclerosis in the aorta: Implications for plaque vulnerability. Circulation 2002, 105:2504–2511.PubMedCrossRefGoogle Scholar
  9. 9.
    Moreno PR, Purushothaman KR, Fuster V, et al.: Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 2004, 110:2032–2038.PubMedCrossRefGoogle Scholar
  10. 10.
    Fleiner M, Kummer M, Mirlacher M, et al.: Arterial neovascularization and inflammation in vulnerable patients: early and late signs of symptomatic atherosclerosis. Circulation 2004, 110:2843–2850.PubMedCrossRefGoogle Scholar
  11. 11.
    Kolodgie FD, Gold HK, Burke AP, et al.: Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 2003, 349:2316–2325.PubMedCrossRefGoogle Scholar
  12. 12.
    Mazurek T, Zhang L, Zalewski A, et al.: Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003, 108:2460–2466.PubMedCrossRefGoogle Scholar
  13. 13.
    Litovsky S, Vela D, Burke A, et al.: Periadventitial fat inflammation may be a novel marker of plaque vulnerability. In press.Google Scholar
  14. 14.
    Gossl M, Malyar NM, Rosol M, et al.: Impact of coronary vasa vasorum functional structure on coronary vessel wall perfusion distribution. Am J Physiol Heart Circ Physiol 2003, 285:H2019-H2026.PubMedGoogle Scholar
  15. 15.
    Wilson SH, Herrmann J, Lerman LO, et al.: Simvastatin preserves the structure of coronary adventitial vasa vasorum in experimental hypercholesterolemia independent of lipid lowering. Circulation 2002, 105:415–418.PubMedCrossRefGoogle Scholar
  16. 16.
    Winter PM, Morawski AM, Caruthers SD, et al.: Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles. Circulation 2003, 108:2270–2274.PubMedCrossRefGoogle Scholar
  17. 17.
    Moulton KS, Heller E, Konerding MA, et al.: Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 1999, 99:1726–1732.PubMedGoogle Scholar
  18. 18.
    Yuk IH, Olsen MM, Geyer S, Forestell SP: Perfusion cultures of human tumor cells: a scalable production platform for oncolytic adenoviral vectors. Biotechnol Bioeng 2004, 86:637–642.PubMedCrossRefGoogle Scholar
  19. 19.
    Weber MA, Thilmann C, Lichy MP, et al.: Assessment of irradiated brain metastases by means of arterial spin-labeling and dynamic susceptibility-weighted contrast-enhanced perfusion MRI: initial results. Invest Radiol 2004, 39:277–287.PubMedCrossRefGoogle Scholar
  20. 20.
    Padhani AR, Dzik-Jurasz A: Perfusion MR imaging of extra-cranial tumor angiogenesis. Top Magn Reson Imaging 2004, 15:41–57.PubMedCrossRefGoogle Scholar
  21. 21.
    Kaul S: Instrumentation for contrast echocardiography: technology and techniques. Am J Cardiol 2002, 90:8J-14J.PubMedCrossRefGoogle Scholar
  22. 22.
    Stewart M: Contrast echocardiography. Heart 2003, 89:342–348.PubMedCrossRefGoogle Scholar
  23. 23.
    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:H450-H457.PubMedCrossRefGoogle Scholar
  24. 24.
    Lanza GM, Wickline SA: Targeted ultrasonic contrast agents for molecular imaging and therapy. Prog Cardiovasc Dis 2001, 44:13–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Hamilton AJ, Huang SL, Warnick D, et al.: Intravascular ultrasound molecular imaging of atheroma components in vivo. J Am Coll Cardiol 2004, 43:453–460.PubMedCrossRefGoogle Scholar
  26. 26.
    Lee TY, Purdie TG, Stewart E: CT imaging of angiogenesis. J Nucl Med 2003, 47:171–187.Google Scholar
  27. 27.
    Yuan C, Kerwin WS, Ferguson MS, et al.: Contrast-enhanced high resolution MRI for atherosclerotic carotid artery tissue characterization. J Magn Reson Imaging 2002, 15:62–67.PubMedCrossRefGoogle Scholar
  28. 28.
    Dijkstra J, Koning G, Reiber JH: Quantitative measurements in IVUS images. Int J Card Imaging 1999, 15:513–522.PubMedCrossRefGoogle Scholar
  29. 29.
    Klingensmith JD, Shekhar R, Vince DG: Evaluation of three-dimensional segmentation algorithms for the identification of luminal and medial-adventitial borders in intravascular ultrasound images. IEEE Trans Med Imag 2000, 19:996–1011.CrossRefGoogle Scholar
  30. 30.
    von Birgelen C, de Vrey EA, Mintz GS, et al.: ECG-gated three-dimensional intravascular ultrasound: feasibility and reproducibility of an automated analysis of coronary lumen and atherosclerotic plaque dimensions in humans. Circulation 1998, 96:2944–2952.Google Scholar
  31. 31.
    Zhu H, Oakeson KD, Friedman MH: Retrieval of cardiac phase from IVUS sequences. Proc SPIE Med Imaging: Ultrasonic Imaging and Signal Processing, 2003, 47:135–146.Google Scholar
  32. 32.
    Cachard C, Finet G, Bouakaz A, et al.: Ultrasound contrast agent in intravascular echography: an in vitro study. Ultrasound Med Biol 1997, 23:705–717.PubMedCrossRefGoogle Scholar
  33. 33.
    Lindner JR, Song J, Xu F, et al.: Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes. Circulation 2000, 102:2745–2750.PubMedGoogle Scholar
  34. 34.
    Hartley CJ, Cheirif J, Collier KR, et al.: Doppler quantification of echo-contrast injections in-vivo. Ultrasound Med Biol 1993, 19:269–278.PubMedCrossRefGoogle Scholar
  35. 35.
    Gossl M, Rosol M, Malyar NM, et al.: Functional anatomy and hemodynamic characteristics of vasa vasorum in the walls of porcine coronary arteries. Anat Rec 2003, 272A:526–537.CrossRefGoogle Scholar
  36. 36.
    Casscells W, Hassan K, Vaseghi MF, et al.: Plaque blush, branch location, and calcification are angiographic predictors of progression of mild to moderate coronary stenoses. Am Heart J 2003, 145:813–820.PubMedCrossRefGoogle Scholar
  37. 37.
    Kerwin W, Hooker A, Spilker M, et al.: Quantitative magnetic resonance imaging analysis of neovasculature volume in carotid atherosclerotic plaque. Circulation 2003, 107:851–856.PubMedCrossRefGoogle Scholar
  38. 38.
    Tom EM, Lu E, Felix MM, Varghese R: In vivo microbubble binding to inflammatory endothelium via selectin targeting by Sialyl Lexis X. Program and abstracts from the American College of Cardiology 53rd Annual Scientific Session. New Orleans, Louisiana, 2004:1001–1033.Google Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Stéphane Carlier
  • Ioannis A. Kakadiaris
  • Nabil Dib
  • Manolis Vavuranakis
  • Sean M. O’Malley
  • Khawar Gul
  • Craig J. Hartley
  • Ralph Metcalfe
  • Roxana Mehran
  • Christodoulos Stefanadis
  • Erling Falk
  • Gregg Stone
  • Martin Leon
  • Morteza Naghavi
    • 1
  1. 1.Association for Eradication of Heart Attack-AEHAHoustonUSA

Personalised recommendations