Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Intravascular imaging of vulnerable coronary plaque: current and future concepts

Nature Reviews Cardiology volume 8, pages 131–139 (2011)Cite this article

Subjects

Abstract

Advances in coronary imaging are needed to enable the early detection of plaque segments considered to be 'vulnerable' for causing clinical events. Pathological studies have contributed to our current understanding of these vulnerable or unstable segments of plaque. Intravascular ultrasonography (IVUS) has provided insights into the morphology of atherosclerosis, the mediators of plaque progression and the factors associated with acute coronary syndrome (ACS). In addition, the demonstration of pancoronary arterial instability has highlighted that ACS involves a multifocal disease process. Various second-generation intravascular imaging technologies—employing advanced processing of ultrasound radiofrequency backscatter signals, light-based imaging, spectroscopic imaging and molecular targeting—possess inherent advantages for the identification of meaningful surrogates of plaque instability. The fusion of these imaging technologies within a single imaging catheter is likely to allow for greater synergism in image quality and early disease detection. However, natural-history studies to validate the use of these novel imaging tools for enhanced risk prediction are needed before these strategies can be incorporated into mainstream clinical practice.

Key Points

  • Prevailing views of vulnerable atherosclerotic coronary plaque features are primarily based upon the 'plaque–rupture' hypothesis, which is predominantly derived from pathological observations at autopsy

  • Intravascular ultrasonography has demonstrated that acute and unstable coronary syndromes involve a multifocal process of pancoronary arterial instability with multiple plaque rupture and substantial atheroma burden

  • Second-generation intravascular imaging modalities employ ultrasound radiofrequency backscatter signal processing, light-based imaging, and spectroscopic imaging to enhance our imaging capabilities; however, each of these approaches requires further development and validation

  • Experimental models of atherosclerosis featuring plaque rupture will enhance our ability to image important mechanisms of plaque vulnerability, facilitating the development of novel antiatherosclerotic therapeutics and prognostic algorithms

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Images obtained using various IVUS techniques.
Figure 2: The correlation between catheter-based NIRS imaging and histology.
Figure 3: The combination of NIRS technology with an IVUS catheter.
Figure 4: Images obtained using OCT coronary imaging.

Similar content being viewed by others

References

  1. Herrick, J. B. Landmark article (JAMA 1912). Clinical features of sudden obstruction of the coronary arteries. By James B. Herrick. JAMA 250, 1757–1765 (1983).

    Article  CAS  Google Scholar 

  2. Davies, M. J. & Thomas, A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N. Engl. J. Med. 310, 1137–1140 (1984).

    Article  CAS  Google Scholar 

  3. DeWood, M. A. et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N. Engl. J. Med. 303, 897–902 (1980).

    Article  CAS  Google Scholar 

  4. Ambrose, J. A. et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J. Am. Coll. Cardiol. 12, 56–62 (1988).

    Article  CAS  Google Scholar 

  5. Glagov, S., Weisenberg, E., Zarins, C. K., Stankunavicius, R. & Kolettis, G. J. Compensatory enlargement of human atherosclerotic coronary arteries. N. Engl. J. Med. 316, 1371–1375 (1987).

    Article  CAS  Google Scholar 

  6. Nicholls, S. J., Tuzcu, E. M., Sipahi, I., Schoenhagen, P. & Nissen, S. E. Intravascular ultrasound in cardiovascular medicine. Circulation 114, e55–e59 (2006).

    Article  Google Scholar 

  7. Muller, J. E., Tofler, G. H. & Stone, P. H. Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 79, 733–743 (1989).

    Article  CAS  Google Scholar 

  8. Finn, A. V., Nakano, M., Narula, J., Kolodgie, F. D. & Virmani, R. Concept of vulnerable/unstable plaque. Arterioscler. Thromb. Vasc. Biol. 30, 1282–1292 (2010).

    Article  CAS  Google Scholar 

  9. Burke, A. P. et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N. Engl. J. Med. 336, 1276–1282 (1997).

    Article  CAS  Google Scholar 

  10. Rioufol, G. et al. Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation 106, 804–808 (2002).

    Article  CAS  Google Scholar 

  11. Hong, M. K. et al. Comparison of coronary plaque rupture between stable angina and acute myocardial infarction: a three-vessel intravascular ultrasound study in 235 patients. Circulation 110, 928–933 (2004).

    Article  Google Scholar 

  12. Mintz, G. S. et al. Atherosclerosis in angiographically “normal” coronary artery reference segments: an intravascular ultrasound study with clinical correlations. J. Am. Coll. Cardiol. 25, 1479–1485 (1995).

    Article  CAS  Google Scholar 

  13. Porter, T. R. et al. Intravascular ultrasound study of angiographically mildly diseased coronary arteries. J. Am. Coll. Cardiol. 22, 1858–1865 (1993).

    Article  CAS  Google Scholar 

  14. Schoenhagen, P., Ziada, K. M., Vince, D. G., Nissen, S. E. & Tuzcu, E. M. Arterial remodeling and coronary artery disease: the concept of “dilated” versus “obstructive” coronary atherosclerosis. J. Am. Coll. Cardiol. 38, 297–306 (2001).

    Article  CAS  Google Scholar 

  15. Smits, P. C., Pasterkamp G., de Jaegere P. P., de Feyter, P. J. & Borst, C. Angioscopic complex lesions are predominantly compensatory enlarged: an angioscopy and intracoronary ultrasound study. Cardiovasc. Res. 41, 458–464 (1999).

    Article  CAS  Google Scholar 

  16. Varnava, A. M., Mills, P. G. & Davies, M. J. Relationship between coronary artery remodeling and plaque vulnerability. Circulation 105, 939–943 (2002).

    Article  Google Scholar 

  17. Schoenhagen, P. et al. Extent and direction of arterial remodeling in stable versus unstable coronary syndromes. An intravascular ultrasound study. Circulation 101, 598–603 (2000).

    Article  CAS  Google Scholar 

  18. Naghavi, M. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 108, 1664–1672 (2003).

    Article  Google Scholar 

  19. Maehara, A. et al. Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound. J. Am. Coll. Cardiol. 40, 904–910 (2002).

    Article  Google Scholar 

  20. Jeremias, A. et al. Coronary artery compliance and adaptive vessel remodelling in patients with stable and unstable coronary artery disease. Heart 84, 314–319 (2000).

    Article  CAS  Google Scholar 

  21. Takano, M. et al. Mechanical and structural characteristics of vulnerable plaques: analysis by coronary angioscopy and intravascular ultrasound. J. Am. Coll. Cardiol. 38, 99–104 (2001).

    Article  CAS  Google Scholar 

  22. Fujii, K. et al. Intravascular ultrasound assessment of ulcerated ruptured plaques: a comparison of culprit and nonculprit lesions of patients with acute coronary syndromes and lesions in patients without acute coronary syndromes. Circulation 108, 2473–2478 (2003).

    Article  Google Scholar 

  23. Fujii, K. et al. Intravascular ultrasound profile analysis of ruptured coronary plaques. Am. J. Cardiol. 98, 429–435 (2006).

    Article  Google Scholar 

  24. Schartl, M. et al. Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease. Circulation 104, 387–392 (2001).

    Article  CAS  Google Scholar 

  25. Tardif, J. C. et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 297, 1675–1682 (2007).

    Article  Google Scholar 

  26. Nair, A., Kuban, B. D., Obuchowski, N. & Vince, D. G. Assessing spectral algorithms to predict atherosclerotic plaque composition with normalized and raw intravascular ultrasound data. Ultrasound Med. Biol. 27, 1319–1331 (2001).

    Article  CAS  Google Scholar 

  27. Nair, A. et al. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation 106, 2200–2206 (2002).

    Article  Google Scholar 

  28. Nair, A., Margolis, M. P., Kuban, B. D. & Vince, D. G. Automated coronary plaque characterisation with intravascular ultrasound backscatter: ex vivo validation. EuroIntervention 3, 113–120 (2007).

    Google Scholar 

  29. Wickline, S. A. et al. Beyond intravascular imaging: quantitative ultrasonic tissue characterization of vascular pathology. IEEE Ultrasonics Symp. 3, 1589–1597 (1994).

    Article  Google Scholar 

  30. Okubo, M. et al. Tissue characterization of coronary plaques: comparison of integrated backscatter intravascular ultrasound with virtual histology intravascular ultrasound. Circ. J. 72, 1631–1639 (2008).

    Article  Google Scholar 

  31. Kawasaki, M. et al. Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesions using ultrasound integrated backscatter: comparison between histology and integrated backscatter images. J. Am. Coll. Cardiol. 38, 486–492 (2001).

    Article  CAS  Google Scholar 

  32. Sathyanarayana, S., Carlier, S., Li, W. & Thomas, L. Characterisation of atherosclerotic plaque by spectral similarity of radiofrequency intravascular ultrasound signals. EuroIntervention 5, 133–139 (2009).

    Article  Google Scholar 

  33. Rodriguez-Granillo, G. A. et al. In vivo intravascular ultrasound-derived thin-cap fibroatheroma detection using ultrasound radiofrequency data analysis. J. Am. Coll. Cardiol. 46, 2038–2042 (2005).

    Article  Google Scholar 

  34. Hong, M. K. et al. A three-vessel virtual histology intravascular ultrasound analysis of frequency and distribution of thin-cap fibroatheromas in patients with acute coronary syndrome or stable angina pectoris. Am. J. Cardiol. 101, 568–572 (2008).

    Article  Google Scholar 

  35. Kubo, T. et al. The dynamic nature of coronary artery lesion morphology assessed by serial virtual histology intravascular ultrasound tissue characterization. J. Am. Coll. Cardiol. 55, 1590–1597 (2010).

    Article  CAS  Google Scholar 

  36. Stone, G. W. Providing regional observation to study predictors of events in the coronary tree—the PROSPECT trial. Presented at the Transcatheter Cardiovascular Therapeutics conference (San Fransisco, 2009).

    Google Scholar 

  37. de Korte, C. L., van der Steen, A. F., Céspedes, E. I. & Pasterkamp, G. Intravascular ultrasound elastography in human arteries: initial experience in vitro. Ultrasound Med. Biol. 24, 401–408 (1998).

    Article  CAS  Google Scholar 

  38. Van Mieghem, C. A. et al. Noninvasive detection of subclinical coronary atherosclerosis coupled with assessment of changes in plaque characteristics using novel invasive imaging modalities: the Integrated Biomarker and Imaging Study (IBIS). J. Am. Coll. Cardiol. 47, 1134–1142 (2006).

    Article  Google Scholar 

  39. Schaar, J. A. et al. Incidence of high-strain patterns in human coronary arteries: assessment with three-dimensional intravascular palpography and correlation with clinical presentation. Circulation 109, 2716–2719 (2004).

    Article  Google Scholar 

  40. Serruys, P. W. et al. Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 118, 1172–1182 (2008).

    Article  CAS  Google Scholar 

  41. Thim, T. et al. Unreliable assessment of necrotic core by virtual histology intravascular ultrasound in porcine coronary artery disease. Circ. Cardiovasc. Imaging 3, 384–391 (2010).

    Article  Google Scholar 

  42. Kubo, T. et al. Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. J. Am. Coll. Cardiol. 50, 933–939 (2007).

    Article  Google Scholar 

  43. Cassis, L. A. & Lodder, R. A. Near-IR imaging of atheromas in living arterial tissue. Anal. Chem. 65, 1247–1256 (1993).

    Article  CAS  Google Scholar 

  44. Jaross, W., Neumeister, V., Lattke, P. & Schuh, D. Determination of cholesterol in atherosclerotic plaques using near infrared diffuse reflection spectroscopy. Atherosclerosis 147, 327–337 (1999).

    Article  CAS  Google Scholar 

  45. Gardner, C. M. et al. Detection of lipid core coronary plaques in autopsy specimens with a novel catheter-based near-infrared spectroscopy system. JACC Cardiovasc. Imaging 1, 638–648 (2008).

    Article  Google Scholar 

  46. Waxman, S. et al. In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques: initial results of the SPECTACL study. JACC Cardiovasc. Imaging 2, 858–868 (2009).

    Article  Google Scholar 

  47. ClinicalTrials.gov. Study of near infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) combination coronary catheter (SAVOIR) [online], (2010).

  48. Bruggink, J. L. et al. Spectroscopy to improve identification of vulnerable plaques in cardiovascular disease. Int. J. Cardiovasc. Imaging 26, 111–119 (2010).

    Article  Google Scholar 

  49. Nazemi, J. H. & Brennan, J. F. Lipid concentrations in human coronary artery determined with high wavenumber Raman shifted light. J. Biomed. Opt. 14, 034009 (2009).

    Article  Google Scholar 

  50. Römer, T. J., et al. Intravascular ultrasound combined with Raman spectroscopy to localize and quantify cholesterol and calcium salts in atherosclerotic coronary arteries. Arterioscler. Thromb. Vasc. Biol. 20, 478–483 (2000).

    Article  Google Scholar 

  51. Buschman, H. P. et al. Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy. Cardiovasc. Pathol. 10, 59–68 (2001).

    Article  CAS  Google Scholar 

  52. Prati, F. et al. Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur. Heart J. 31, 401–415 (2010).

    Article  Google Scholar 

  53. Prati, F. et al. Safety and feasibility of a new non-occlusive technique for facilitated intracoronary optical coherence tomography (OCT) acquisition in various clinical and anatomical scenarios. EuroIntervention 3, 365–370 (2007).

    Article  Google Scholar 

  54. Serruys, P. W. et al. A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet 373, 897–910 (2009).

    Article  CAS  Google Scholar 

  55. Cook, S. et al. Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation. Circulation 115, 2426–2434 (2007).

    Article  CAS  Google Scholar 

  56. Finn, A. V. et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation 115, 2435–2441 (2007).

    Article  Google Scholar 

  57. Joner, M. et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J. Am. Coll. Cardiol. 48, 193–202 (2006).

    Article  Google Scholar 

  58. Jang, I. K. et al. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation 111, 1551–1555 (2005).

    Article  Google Scholar 

  59. Kubo, T. et al. Multiple coronary lesion instability in patients with acute myocardial infarction as determined by optical coherence tomography. Am. J. Cardiol. 105, 318–322 (2010).

    Article  Google Scholar 

  60. MacNeill, B. D. et al. Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease. J. Am. Coll. Cardiol. 44, 972–979 (2004).

    Article  Google Scholar 

  61. Raffel, O. C. et al. Relationship between a systemic inflammatory marker, plaque inflammation, and plaque characteristics determined by intravascular optical coherence tomography. Arterioscler. Thromb. Vasc. Biol. 27, 1820–1827 (2007).

    Article  CAS  Google Scholar 

  62. Li, Q. X. et al. Relationship between plasma inflammatory markers and plaque fibrous cap thickness determined by intravascular optical coherence tomography. Heart 96, 196–201 (2010).

    Article  CAS  Google Scholar 

  63. Tanaka, A. et al. Morphology of exertion-triggered plaque rupture in patients with acute coronary syndrome: an optical coherence tomography study. Circulation 118, 2368–2373 (2008).

    Article  Google Scholar 

  64. Kawasaki, M. et al. Diagnostic accuracy of optical coherence tomography and integrated backscatter intravascular ultrasound images for tissue characterization of human coronary plaques. J. Am. Coll. Cardiol. 48, 81–88 (2006).

    Article  Google Scholar 

  65. Manfrini, O. et al. Sources of error and interpretation of plaque morphology by optical coherence tomography. Am. J. Cardiol. 98, 156–159 (2006).

    Article  Google Scholar 

  66. Yuan, S. et al. Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging. Phys. Med. Biol. 55, 191–206 (2010).

    Article  CAS  Google Scholar 

  67. Li, X. et al. High-resolution coregistered intravascular imaging with integrated ultrasound and optical coherence tomography probe. Appl. Phys. Lett. 97, 133702 (2010).

    Article  Google Scholar 

  68. Slager, C. J. et al. True 3-dimensional reconstruction of coronary arteries in patients by fusion of angiography and IVUS (ANGUS) and its quantitative validation. Circulation 102, 511–516 (2000).

    Article  CAS  Google Scholar 

  69. Krams, R. et al. Evaluation of endothelial shear stress and 3D geometry as factors determining the development of atherosclerosis and remodeling in human coronary arteries in vivo. Combining 3D reconstruction from angiography and IVUS (ANGUS) with computational fluid dynamics. Arterioscler. Thromb. Vasc. Biol. 17, 2061–2065 (1997).

    Article  CAS  Google Scholar 

  70. Coskun, A. U. et al. Reproducibility of coronary lumen, plaque, and vessel wall reconstruction and of endothelial shear stress measurements in vivo in humans. Catheter Cardiovasc. Interv. 60, 67–78 (2003).

    Article  Google Scholar 

  71. Gibson, C. M. et al. Relation of vessel wall shear stress to atherosclerosis progression in human coronary arteries. Arterioscler. Thromb. 13, 310–315 (1993).

    Article  CAS  Google Scholar 

  72. Koskinas, K. C. et al. Natural history of experimental coronary atherosclerosis and vascular remodeling in relation to endothelial shear stress: a serial, in vivo intravascular ultrasound study. Circulation 121, 2092–2101 (2010).

    Article  Google Scholar 

  73. Kolodgie, F. D. et al. Intraplaque hemorrhage and progression of coronary atheroma. N. Engl. J. Med. 349, 2316–2325 (2003).

    Article  CAS  Google Scholar 

  74. Vavuranakis, M. et al. A new method for assessment of plaque vulnerability based on vasa vasorum imaging, by using contrast-enhanced intravascular ultrasound and differential image analysis. Int. J. Cardiol. 130, 23–29 (2008).

    Article  Google Scholar 

  75. Goertz, D. E. et al. Subharmonic contrast intravascular ultrasound for vasa vasorum imaging. Ultrasound Med. Biol. 33, 1859–1872 (2007).

    Article  Google Scholar 

  76. Kaufmann, B. A. Ultrasound molecular imaging of atherosclerosis. Cardiovasc. Res. 83, 617–625 (2009).

    Article  CAS  Google Scholar 

  77. Lindner, J. R. Contrast ultrasound molecular imaging: harnessing the power of bubbles. Cardiovasc. Res. 83, 615–616 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

R. Puri is supported by a Postgraduate Medical Research Scholarship issued jointly from the National Health & Medical Research Council (565579) and the National Heart Foundation of Australia (PC0804045), and a Dawes Scholarship, Hanson Institute. M. I. Worthley is a SA Health Early-to-Mid-Career Practitioner Fellow.

Author information

Authors and Affiliations

  1. Department of Medicine, Cardiovascular Research Centre, University of Adelaide, North Terrace, Adelaide, 5000, SA, Australia

    Rishi Puri & Matthew I. Worthley

  2. Department of Cardiovascular Medicine, Heart and Vascular Institute, Mail Code JJ-65, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195, OH, USA

    Stephen J. Nicholls

Authors
  1. Rishi Puri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew I. Worthley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen J. Nicholls
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

R. Puri researched the data for the article and wrote the article. All authors provided a substantial contribution to discussions of the content and to the review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Stephen J. Nicholls.

Ethics declarations

Competing interests

S. J. Nicholls is a consultant and on the speaker's bureau for Astrazeneca and Roche. He also receives grant/research support from Astrazeneca, Novartis and Resverlogix. R. Puri and M. I. Worthley declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Puri, R., Worthley, M. & Nicholls, S. Intravascular imaging of vulnerable coronary plaque: current and future concepts. Nat Rev Cardiol 8, 131–139 (2011). https://doi.org/10.1038/nrcardio.2010.210

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2010.210

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing