CT Imaging of the Vulnerable Plaque

  • Gary R. Small
  • Benjamin J. W. Chow
Imaging (Q Truong, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Imaging

Opinion statement

Acute coronary syndromes are most often the result of vulnerable atherosclerotic plaque events. Plaques events occur when intimal fibroatheroma in the coronary artery wall becomes vulnerable to erosion or rupture. Such vulnerable plaques can be distinguished from quiescent atheroma by features that have been defined through histopathology and invasive imaging. A challenge for coronary CT angiography has been to identify vulnerable plaques non-invasively. Were this possible, CT angiography could offer comprehensive vessel assessment including stenosis severity and plaque characteristics with the hope of reducing acute coronary events through timely intervention. Over the past decade, advances in invasive imaging techniques have enabled unstable coronary plaques to be accessed more readily. In this fashion it has been possible to correlate invasive appearances to CT angiographic findings in an unprecedented manner. Several CT defined plaque characteristic have now been described to reliably identify unstable plaques. Retrospective studies have demonstrated the utility of these plaque features to predict future acute coronary events. If these can be confirmed in prospective studies, the intrinsic benefits of non-invasive imaging will position coronary CT angiography firmly in our armamentarium to image coronary arteries and help prevent acute coronary events.


Acute coronary syndromes CT angiography Imaging 


Compliance with Ethical Standards

Conflict of Interest

Gary R. Small declares no potential conflicts of interest.

Benjamin J. W. Chow reports grants from TeraRecon and CV Diagnostix.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Bouch DC, Montgomery GL. Cardiac lesions in fatal cases of recent myocardial ischaemia from a coronary care unit. Br Heart J. 1970;32(6):795–803.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J. 2013;34(10):719–28.CrossRefPubMedGoogle Scholar
  3. 3.
    Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the Management of Acute Coronary Syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267–315.CrossRefPubMedGoogle Scholar
  4. 4.
    Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987;316(22):1371–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Schoenhagen P, Ziada KM, Kapadia SR, Crowe TD, Nissen SE, Tuzcu EM. Extent and direction of arterial remodeling in stable versus unstable coronary syndromes: an intravascular ultrasound study. Circulation. 2000;101(6):598–603.CrossRefPubMedGoogle Scholar
  6. 6.
    Smits PC, Pasterkamp G, Quarles van Ufford MA, Eefting FD, Stella PR, de Jaegere PP, et al. Coronary artery disease: arterial remodelling and clinical presentation. Heart. 1999;82(4):461–4.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Gauss S, Achenbach S, Pflederer T, Schuhback A, Daniel WG, Marwan M. Assessment of coronary artery remodelling by dual-source CT: a head-to-head comparison with intravascular ultrasound. Heart. 2011;97(12):991–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Kroner ES, van Velzen JE, Boogers MJ, Siebelink HM, Schalij MJ, Kroft LJ, et al. Positive remodeling on coronary computed tomography as a marker for plaque vulnerability on virtual histology intravascular ultrasound. Am J Cardiol. 2011;107(12):1725–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Ito T, Terashima M, Kaneda H, Nasu K, Matsuo H, Ehara M, et al. Comparison of in vivo assessment of vulnerable plaque by 64-slice multislice computed tomography versus optical coherence tomography. Am J Cardiol. 2011;107(9):1270–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Kashiwagi M, Tanaka A, Kitabata H, Tsujioka H, Kataiwa H, Komukai K, et al. Feasibility of noninvasive assessment of thin-cap fibroatheroma by multidetector computed tomography. JACC Cardiovasc Imaging. 2009;2(12):1412–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Motoyama S, Kondo T, Sarai M, Sugiura A, Harigaya H, Sato T, et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol. 2007;50(4):319–26.CrossRefPubMedGoogle Scholar
  12. 12.
    Wu X, Mintz GS, Xu K, Lansky AJ, Witzenbichler B, Guagliumi G, et al. The relationship between attenuated plaque identified by intravascular ultrasound and no-reflow after stenting in acute myocardial infarction: the HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial. JACC Cardiovasc Interv. 2011;4(5):495–502.CrossRefPubMedGoogle Scholar
  13. 13.
    Dwivedi G, Liu Y, Tewari S, Inacio J, Pelletier-Galarneau M, Chow BJ. Incremental prognostic value of quantified vulnerable plaque by cardiac computed tomography: a pilot study. J Thorac Imaging. 2016;31(6):373–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Pflederer T, Marwan M, Schepis T, Ropers D, Seltmann M, Muschiol G, et al. Characterization of culprit lesions in acute coronary syndromes using coronary dual-source CT angiography. Atherosclerosis. 2010;211(2):437–44.CrossRefPubMedGoogle Scholar
  15. 15.
    Kim SY, Kim KS, Seung MJ, Chung JW, Kim JH, Mun SH, et al. The culprit lesion score on multi-detector computed tomography can detect vulnerable coronary artery plaque. Int J Cardiovasc Imaging. 2010;26(Suppl 2):245–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Kitagawa T, Yamamoto H, Ohhashi N, Okimoto T, Horiguchi J, Hirai N, et al. Comprehensive evaluation of noncalcified coronary plaque characteristics detected using 64-slice computed tomography in patients with proven or suspected coronary artery disease. Am Heart J. 2007;154(6):1191–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Schlett CL, Maurovich-Horvat P, Ferencik M, Alkadhi H, Stolzmann P, Scheffel H, et al. Histogram analysis of lipid-core plaques in coronary computed tomographic angiography: ex vivo validation against histology. Investig Radiol. 2013;48(9):646–53.CrossRefGoogle Scholar
  18. 18.
    Ozaki Y, Okumura M, Ismail TF, Motoyama S, Naruse H, Hattori K, et al. Coronary CT angiographic characteristics of culprit lesions in acute coronary syndromes not related to plaque rupture as defined by optical coherence tomography and angioscopy. Eur Heart J. 2011;32(22):2814–23.CrossRefPubMedGoogle Scholar
  19. 19.
    •• Maurovich-Horvat P, Ferencik M, Voros S, Merkely B, Hoffmann U. Comprehensive plaque assessment by coronary CT angiography. Nat Rev Cardiol. 2014;11(7):390–402. Excellently written, thorough review by active researchers in the field of CT vulnerable plaque imagingCrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Narula J, Nakano M, Virmani R, Kolodgie FD, Petersen R, Newcomb R, et al. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J Am Coll Cardiol. 2013;61(10):1041–51.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol. 2006;47(8 Suppl):C13–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Tanaka A, Shimada K, Yoshida K, Jissyo S, Tanaka H, Sakamoto M, et al. Non-invasive assessment of plaque rupture by 64-slice multidetector computed tomography—comparison with intravascular ultrasound. Circ J. 2008;72(8):1276–81.CrossRefPubMedGoogle Scholar
  23. 23.
    Takamura K, Fujimoto S, Kondo T, Hiki M, Kawaguchi Y, Kato E et al. Incremental prognostic value of coronary computed tomography angiography: high-risk plaque characteristics in asymptomatic patients. J Atheroscler Thromb 2017.
  24. 24.
    Maurovich-Horvat P, Hoffmann U, Vorpahl M, Nakano M, Virmani R, Alkadhi H. The napkin-ring sign: CT signature of high-risk coronary plaques? JACC Cardiovasc Imaging. 2010;3(4):440–4.CrossRefPubMedGoogle Scholar
  25. 25.
    Goldstein JA, Grines C, Fischell T, Virmani R, Rizik D, Muller J, et al. Coronary embolization following balloon dilation of lipid-core plaques. JACC Cardiovasc Imaging. 2009;2(12):1420–4.CrossRefPubMedGoogle Scholar
  26. 26.
    Ferencik M, Mayrhofer T, Puchner SB, Lu MT, Maurovich-Horvat P, Liu T, et al. Computed tomography-based high-risk coronary plaque score to predict acute coronary syndrome among patients with acute chest pain—results from the ROMICAT II trial. J Cardiovasc Comput Tomogr. 2015;9(6):538–45.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Otsuka K, Fukuda S, Tanaka A, Nakanishi K, Taguchi H, Yoshikawa J, et al. Napkin-ring sign on coronary CT angiography for the prediction of acute coronary syndrome. JACC Cardiovasc Imaging. 2013;6(4):448–57.CrossRefPubMedGoogle Scholar
  28. 28.
    Nadjiri J, Hausleiter J, Jahnichen C, Will A, Hendrich E, Martinoff S, et al. Incremental prognostic value of quantitative plaque assessment in coronary CT angiography during 5 years of follow up. J Cardiovasc Comput Tomogr. 2016;10(2):97–104.CrossRefPubMedGoogle Scholar
  29. 29.
    Aikawa E, Nahrendorf M, Figueiredo JL, Swirski FK, Shtatland T, Kohler RH, et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation. 2007;116(24):2841–50.CrossRefPubMedGoogle Scholar
  30. 30.
    • Joshi NV, Vesey AT, Williams MC, Shah AS, Calvert PA, Craighead FH, et al. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet. 2014;383(9918):705–13. An important “landmark” study likely to lead to further work to determine the pathphysiology of calcification of atherosclerotic plaquesCrossRefPubMedGoogle Scholar
  31. 31.
    Hadamitzky M, Achenbach S, Al-Mallah M, Berman D, Budoff M, Cademartiri F, et al. Optimized prognostic score for coronary computed tomographic angiography: results from the CONFIRM registry (COronary CT angiography EvaluatioN for clinical outcomes: an InteRnational multicenter registry). J Am Coll Cardiol. 2013;62(5):468–76.CrossRefPubMedGoogle Scholar
  32. 32.
    Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20(5):1262–75.CrossRefPubMedGoogle Scholar
  33. 33.
    Ehara S, Kobayashi Y, Yoshiyama M, Shimada K, Shimada Y, Fukuda D, et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation. 2004;110(22):3424–9.CrossRefPubMedGoogle Scholar
  34. 34.
    van Velzen JE, de Graaf FR, de Graaf MA, Schuijf JD, Kroft LJ, de Roos A, et al. Comprehensive assessment of spotty calcifications on computed tomography angiography: comparison to plaque characteristics on intravascular ultrasound with radiofrequency backscatter analysis. J Nucl Cardiol. 2011;18(5):893–903.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Vengrenyuk Y, Carlier S, Xanthos S, Cardoso L, Ganatos P, Virmani R, et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc Natl Acad Sci U S A. 2006;103(40):14678–83.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tonino PA, De BB, Pijls NH, Siebert U, Ikeno F, Veer M, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213–24.CrossRefPubMedGoogle Scholar
  37. 37.
    Pijls NH, Fearon WF, Tonino PA, Siebert U, Ikeno F, Bornschein B, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (fractional flow reserve versus angiography for multivessel evaluation) study. J Am Coll Cardiol. 2010;56(3):177–84.CrossRefPubMedGoogle Scholar
  38. 38.
    Kini AS, Baber U, Kovacic JC, Limaye A, Ali ZA, Sweeny J, et al. Changes in plaque lipid content after short-term intensive versus standard statin therapy: the YELLOW trial (reduction in yellow plaque by aggressive lipid-lowering therapy). J Am Coll Cardiol. 2013;62(1):21–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Hachamovitch R, Rozanski A, Shaw LJ, Stone GW, Thomson LE, Friedman JD, et al. Impact of ischaemia and scar on the therapeutic benefit derived from myocardial revascularization vs. medical therapy among patients undergoing stress-rest myocardial perfusion scintigraphy. Eur Heart J. 2011;32(8):1012–24.CrossRefPubMedGoogle Scholar
  40. 40.
    Versteeg D, Hoefer IE, Schoneveld AH, de Kleijn DP, Busser E, Strijder C, et al. Monocyte toll-like receptor 2 and 4 responses and expression following percutaneous coronary intervention: association with lesion stenosis and fractional flow reserve. Heart. 2008;94(6):770–6.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Rogers IS, Nasir K, Figueroa AL, Cury RC, Hoffmann U, Vermylen DA, et al. Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. JACC Cardiovasc Imaging. 2010;3(4):388–97.CrossRefPubMedGoogle Scholar
  42. 42.
    Taylor CA, Fonte TA, Min JK. Computational fluid dynamics applied to cardiac computed tomography for noninvasive quantification of fractional flow reserve: scientific basis. J Am Coll Cardiol. 2013;61(22):2233–41.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Nakanishi R, Matsumoto S, Alani A, Li D, Kitslaar PH, Broersen A, et al. Diagnostic performance of transluminal attenuation gradient and fractional flow reserve by coronary computed tomographic angiography (FFRCT) compared to invasive FFR: a sub-group analysis from the DISCOVER-FLOW and DeFACTO studies. Int J Cardiovasc Imaging. 2015;31(6):1251–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008;359(22):2324–36.CrossRefPubMedGoogle Scholar
  45. 45.
    de Araujo GP, Garcia-Garcia HM, Dores H, Carvalho MS, Jeronimo SP, Marques H, et al. Coronary computed tomography angiography-adapted Leaman score as a tool to noninvasively quantify total coronary atherosclerotic burden. Int J Cardiovasc Imaging. 2013;29(7):1575–84.CrossRefGoogle Scholar
  46. 46.
    Deseive S, Shaw LJ, Min JK, Achenbach S, Andreini D, Al-Mallah MH, et al. Improved 5-year prediction of all-cause mortality by coronary CT angiography applying the CONFIRM score. Eur Heart J Cardiovasc Imaging. 2017;18(3):286–93.CrossRefPubMedGoogle Scholar
  47. 47.
    Hoffmann U, Bamberg F, Chae CU, Nichols JH, Rogers IS, Seneviratne SK, et al. Coronary computed tomography angiography for early triage of patients with acute chest pain: the ROMICAT (rule out myocardial infarction using computer assisted tomography) trial. J Am Coll Cardiol. 2009;53(18):1642–50.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Hoffmann U, Truong QA, Schoenfeld DA, Chou ET, Woodard PK, Nagurney JT, et al. Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med. 2012;367(4):299–308.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Ferencik M, Schlett CL, Ghoshhajra BB, Kriegel MF, Joshi SB, Maurovich-Horvat P, et al. A computed tomography-based coronary lesion score to predict acute coronary syndrome among patients with acute chest pain and significant coronary stenosis on coronary computed tomographic angiogram. Am J Cardiol. 2012;110(2):183–9.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Puchner SB, Liu T, Mayrhofer T, Truong QA, Lee H, Fleg JL, et al. High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial. J Am Coll Cardiol. 2014;64(7):684–92.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Padmanabhan P, Kumar A, Kumar S, Chaudhary RK, Gulyas B. Nanoparticles in practice for molecular-imaging applications: an overview. Acta Biomater. 2016;41:1–16.CrossRefPubMedGoogle Scholar
  52. 52.
    Chhour P, Naha PC, O’Neill SM, Litt HI, Reilly MP, Ferrari VA, et al. Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography. Biomaterials. 2016;87:93–103.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Qin J, Peng C, Zhao B, Ye K, Yuan F, Peng Z, et al. Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles. Int J Nanomedicine. 2014;9:5575–90.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Skajaa T, Cormode DP, Falk E, Mulder WJ, Fisher EA, Fayad ZA. High-density lipoprotein-based contrast agents for multimodal imaging of atherosclerosis. Arterioscler Thromb Vasc Biol. 2010;30(2):169–76.CrossRefPubMedGoogle Scholar
  55. 55.
    Hyafil F, Cornily JC, Feig JE, Gordon R, Vucic E, Amirbekian V, et al. Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography. Nat Med. 2007;13(5):636–41.CrossRefPubMedGoogle Scholar
  56. 56.
    • CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet 2015; 385(9985):2383–2391. piece of work determining the clinical impact of CT and has led to national guideline changes in the UK.
  57. 57.
    • Williams MC, Hunter A, ASV S, Assi V, Lewis S, Smith J, et al. Use of coronary computed tomographic angiography to guide management of patients with coronary disease. J Am Coll Cardiol. 2016;67(15):1759–68. Innovative piece of work determining the clinical impact of CT and has led to national guideline changes in the UKCrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    National Institute for Health and Clinical Excellence. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin (update) CG95. National Institute for Health and Clinical Excellence 2016.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Medicine (Cardiology)University of Ottawa Heart InstituteOttawaCanada

Personalised recommendations