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:

Comprehensive plaque assessment by coronary CT angiography

Key Points

  • Most acute coronary events result from sudden luminal thrombosis due to rupture of an atherosclerotic plaque

  • Modern computed tomography (CT) scanners enable robust coronary plaque characterization and quantification

  • Large plaque volume, low CT attenuation, napkin-ring sign, positive remodelling, and spotty calcification are all associated with plaques vulnerable to rupture

  • Computational fluid dynamic simulation enables plaque-specific endothelial shear stress and fractional flow reserve assessment, and thus permits functional characterization of plaques

  • Coupling individual plaque morphology with plaque-specific functional data will enable new noninvasive detection of vulnerable plaques with CT

Abstract

Most acute coronary syndromes are caused by sudden luminal thrombosis due to atherosclerotic plaque rupture or erosion. Preventing such an event seems to be the only effective strategy to reduce mortality and morbidity of coronary heart disease. Coronary lesions prone to rupture have a distinct morphology compared with stable plaques, and provide a unique opportunity for noninvasive imaging to identify vulnerable plaques before they lead to clinical events. The submillimeter spatial resolution and excellent image quality of modern computed tomography (CT) scanners allow coronary atherosclerotic lesions to be detected, characterized, and quantified. Large plaque volume, low CT attenuation, napkin-ring sign, positive remodelling, and spotty calcification are all associated with a high risk of acute cardiovascular events in patients. Computation fluid dynamics allow the calculation of lesion-specific endothelial shear stress and fractional flow reserve, which add functional information to plaque assessment using CT. The combination of morphologic and functional characteristics of coronary plaques might enable noninvasive detection of vulnerable plaques in the future.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: The morphology and functional characteristics of stable and vulnerable plaques.
Figure 2: Example of plaque characterization and quantification using a dedicated automated software tool and CCTA data set.
Figure 3: Cross-sectional CT showing coronary plaque with napkin-ring sign and spotty calcification.
Figure 4: Traditional and attenuation pattern-based plaque classification schemes in CCTA.
Figure 5: Time averaged ESS map of a left coronary artery derived by computation fluid dynamics simulation.
Figure 6: In histopathological studies of patients who suffered sudden cardiac death, 40% of nonruptured TCFAs also caused >75% luminal narrowing.
Figure 7: FFR-CT compared with CCTA and coronary angiogram for the identification of significant stenoses.
Figure 8: An illustration of potential comprehensive plaque assessment with CCTA.

Similar content being viewed by others

References

  1. Mathers, C. D. & Loncar, D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 3, e442 (2006).

    PubMed  PubMed Central  Google Scholar 

  2. WHO. Cardiovascular diseases (CVDs) [online], (2013).

  3. Go, A. S. et al. Heart disease and stroke statistics--2014 update: A report from the American Heart Association. Circulation 129, e28–e292 (2014).

    PubMed  Google Scholar 

  4. Heidenreich, P. A. et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation 123, 933–944 (2011).

    PubMed  Google Scholar 

  5. Nabel, E. G. & Braunwald, E. A tale of coronary artery disease and myocardial infarction. N. Engl. J. Med. 366, 54–63 (2012).

    CAS  PubMed  Google Scholar 

  6. Libby, P. Mechanisms of acute coronary syndromes and their implications for therapy. N. Engl. J. Med. 368, 2004–2013 (2013).

    CAS  PubMed  Google Scholar 

  7. Narula, J. & Strauss, H. W. The popcorn plaques. Nat. Med. 13, 532–534 (2007).

    CAS  PubMed  Google Scholar 

  8. Braunwald, E. Epilogue: what do clinicians expect from imagers? J. Am. Coll. Cardiol. 47 (Suppl.), C101–C103 (2006).

    PubMed  Google Scholar 

  9. Waxman, S., Ishibashi, F. & Muller, J. E. Detection and treatment of vulnerable plaques and vulnerable patients: novel approaches to prevention of coronary events. Circulation 114, 2390–2411 (2006).

    PubMed  Google Scholar 

  10. 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).

    CAS  PubMed  Google Scholar 

  11. Falk, E., Nakano, M., Bentzon, J. F., Finn, A. V. & Virmani, R. Update on acute coronary syndromes: the pathologists' view. Eur. Heart J. 34, 719–728 (2013).

    CAS  PubMed  Google Scholar 

  12. Virmani, R., Kolodgie, F. D., Burke, A. P., Farb, A. & Schwartz, S. M. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 20, 1262–1275 (2000).

    CAS  PubMed  Google Scholar 

  13. Narula, J. et al. Arithmetic of vulnerable plaques for noninvasive imaging. Nat. Clin. Pract. Cardiovasc. Med. 5 (Suppl. 2), S2–S10 (2008).

    PubMed  Google Scholar 

  14. 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).

    CAS  PubMed  Google Scholar 

  15. Narula, J. 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. 61, 1041–1051 (2013).

    PubMed  PubMed Central  Google Scholar 

  16. Ferencik, M. 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. 110, 183–189 (2012).

    PubMed  PubMed Central  Google Scholar 

  17. Achenbach, S. et al. CV Imaging: What was new in 2012? JACC Cardiovasc. Imaging 6, 714–734 (2013).

    PubMed  Google Scholar 

  18. Achenbach, S. & Raggi, P. Imaging of coronary atherosclerosis by computed tomography. Eur. Heart J. 31, 1442–1448 (2010).

    PubMed  Google Scholar 

  19. Virmani, R., Burke, A. P., Farb, A. & Kolodgie, F. D. Pathology of the vulnerable plaque. J. Am. Coll. Cardiol. 47 (Suppl.), C13–C18 (2006).

    CAS  PubMed  Google Scholar 

  20. Achenbach, S. Can CT detect the vulnerable coronary plaque? Int. J. Cardiovasc. Imaging 24, 311–312 (2008).

    PubMed  Google Scholar 

  21. Kolodgie, F. D. et al. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr. Opin. Cardiol. 16, 285–292 (2001).

    CAS  PubMed  Google Scholar 

  22. van der Giessen, A. G. et al. Reproducibility, accuracy, and predictors of accuracy for the detection of coronary atherosclerotic plaque composition by computed tomography: an ex vivo comparison to intravascular ultrasound. Invest. Radiol. 45, 693–701 (2010).

    PubMed  Google Scholar 

  23. Hoffmann, U., Ferencik, M., Cury, R. C. & Pena, A. J. Coronary CT angiography. J. Nucl. Med. 47, 797–806 (2006).

    PubMed  Google Scholar 

  24. Stone, G. W. et al. A prospective natural-history study of coronary atherosclerosis. N. Engl. J. Med. 364, 226–235 (2011).

    CAS  PubMed  Google Scholar 

  25. Blackmon, K. N. et al. Reproducibility of automated noncalcified coronary artery plaque burden assessment at coronary CT angiography. J. Thorac. Imaging 24, 96–102 (2009).

    PubMed  Google Scholar 

  26. Hoffmann, U. et al. Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography. J. Am. Coll. Cardiol. 47, 1655–1662 (2006).

    PubMed  Google Scholar 

  27. Klass, O. et al. Coronary plaque imaging with 256-slice multidetector computed tomography: interobserver variability of volumetric lesion parameters with semiautomatic plaque analysis software. Int. J. Cardiovasc. Imaging 26, 711–720 (2010).

    PubMed  Google Scholar 

  28. Brodoefel, H. et al. Coronary plaque quantification by voxel analysis: dual-source MDCT angiography versus intravascular sonography. AJR Am. J. Roentgenol. 192, W84–W89 (2009).

    PubMed  PubMed Central  Google Scholar 

  29. Schepis, T. et al. Quantification of non-calcified coronary atherosclerotic plaques with dual-source computed tomography: comparison with intravascular ultrasound. Heart 96, 610–615 (2010).

    PubMed  Google Scholar 

  30. Boogers, M. J. et al. Automated quantification of coronary plaque with computed tomography: comparison with intravascular ultrasound using a dedicated registration algorithm for fusion-based quantification. Eur. Heart J. 33, 1007–1016 (2012).

    PubMed  Google Scholar 

  31. Voros, S. et al. Prospective validation of standardized, 3-dimensional, quantitative coronary computed tomographic plaque measurements using radiofrequency backscatter intravascular ultrasound as reference standard in intermediate coronary arterial lesions: results from the ATLANTA (assessment of tissue characteristics, lesion morphology, and hemodynamics by angiography with fractional flow reserve, intravascular ultrasound and virtual histology, and noninvasive computed tomography in atherosclerotic plaques) I study. JACC Cardiovasc. Interv. 4, 198–208 (2011).

    PubMed  Google Scholar 

  32. Voros, S. et al. Coronary atherosclerosis imaging by coronary CT angiography: current status, correlation with intravascular interrogation and meta-analysis. JACC Cardiovasc. Imaging 4, 537–548 (2011).

    PubMed  Google Scholar 

  33. Oberoi, S. et al. Reproducibility of noncalcified coronary artery plaque burden quantification from coronary CT angiography across different image analysis platforms. AJR Am. J. Roentgenol. 202, W43–W49 (2014).

    PubMed  Google Scholar 

  34. Pflederer, T. et al. Characterization of culprit lesions in acute coronary syndromes using coronary dual-source CT angiography. Atherosclerosis 211, 437–444 (2010).

    CAS  PubMed  Google Scholar 

  35. Madder, R. D., Chinnaiyan, K. M., Marandici, A. M. & Goldstein, J. A. Features of disrupted plaques by coronary computed tomographic angiography: correlates with invasively proven complex lesions. Circ. Cardiovasc. Imaging 4, 105–113 (2011).

    PubMed  Google Scholar 

  36. Motoyama, S. et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J. Am. Coll. Cardiol. 54, 49–57 (2009).

    PubMed  Google Scholar 

  37. Versteylen, M. O. et al. Additive value of semiautomated quantification of coronary artery disease using cardiac computed tomographic angiography to predict future acute coronary syndrome. J. Am. Coll. Cardiol. 61, 2296–2305 (2013).

    PubMed  Google Scholar 

  38. Kristensen, T. S. et al. Prognostic implications of nonobstructive coronary plaques in patients with non-ST-segment elevation myocardial infarction: a multidetector computed tomography study. J. Am. Coll. Cardiol. 58, 502–509 (2011).

    PubMed  Google Scholar 

  39. Papadopoulou, S. L. et al. Natural history of coronary atherosclerosis by multislice computed tomography. JACC Cardiovasc. Imaging 5 (Suppl.), S28–S37 (2012).

    PubMed  Google Scholar 

  40. Schlett, C. L. et al. How to assess non-calcified plaque in CT angiography: delineation methods affect diagnostic accuracy of low-attenuation plaque by CT for lipid-core plaque in histology. Eur. Heart J. Cardiovasc. Imaging 14, 1099–1105 (2013).

    PubMed  Google Scholar 

  41. Becker, C. R., Knez, A., Ohnesorge, B., Schoepf, U. J. & Reiser, M. F. Imaging of noncalcified coronary plaques using helical CT with retrospective ECG gating. AJR Am. J. Roentgenol. 175, 423–424 (2000).

    CAS  PubMed  Google Scholar 

  42. Achenbach, S. et al. Detection of calcified and noncalcified coronary atherosclerotic plaque by contrast-enhanced, submillimeter multidetector spiral computed tomography: a segment-based comparison with intravascular ultrasound. Circulation 109, 14–17 (2004).

    PubMed  Google Scholar 

  43. Pohle, K. et al. Characterization of non-calcified coronary atherosclerotic plaque by multi-detector row CT: comparison to IVUS. Atherosclerosis 190, 174–180 (2007).

    CAS  PubMed  Google Scholar 

  44. Marwan, M. et al. In vivo CT detection of lipid-rich coronary artery atherosclerotic plaques using quantitative histogram analysis: a head to head comparison with IVUS. Atherosclerosis 215, 110–115 (2011).

    CAS  PubMed  Google Scholar 

  45. Schlett, C. L. et al. Histogram analysis of lipid-core plaques in coronary computed tomographic angiography: ex vivo validation against histology. Invest. Radiol. 48, 646–653 (2013).

    PubMed  Google Scholar 

  46. Kashiwagi, M. et al. Feasibility of noninvasive assessment of thin-cap fibroatheroma by multidetector computed tomography. JACC Cardiovasc. Imaging 2, 1412–1419 (2009).

    PubMed  Google Scholar 

  47. Ito, T. et al. Comparison of in vivo assessment of vulnerable plaque by 64-slice multislice computed tomography versus optical coherence tomography. Am. J. Cardiol. 107, 1270–1277 (2011).

    PubMed  Google Scholar 

  48. Achenbach, S. et al. Influence of slice thickness and reconstruction kernel on the computed tomographic attenuation of coronary atherosclerotic plaque. J. Cardiovasc. Comput. Tomogr. 4, 110–115 (2010).

    PubMed  Google Scholar 

  49. Cademartiri, F. et al. Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography. Eur. Radiol. 15, 1426–1431 (2005).

    PubMed  Google Scholar 

  50. Ferencik, M. et al. Arterial wall imaging: evaluation with 16-section multidetector CT in blood vessel phantoms and ex vivo coronary arteries. Radiology 240, 708–716 (2006).

    PubMed  Google Scholar 

  51. Suzuki, S. et al. Accuracy of attenuation measurement of vascular wall in vitro on computed tomography angiography: effect of wall thickness, density of contrast medium, and measurement point. Invest. Radiol. 41, 510–515 (2006).

    PubMed  Google Scholar 

  52. Dey, D. et al. Automated three-dimensional quantification of noncalcified coronary plaque from coronary CT angiography: comparison with intravascular US. Radiology 257, 516–522 (2010).

    PubMed  Google Scholar 

  53. Motoyama, S. et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J. Am. Coll. Cardiol. 50, 319–326 (2007).

    PubMed  Google Scholar 

  54. Ozaki, Y. 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. 32, 2814–2823 (2011).

    PubMed  Google Scholar 

  55. Kim, S. Y. et al. The culprit lesion score on multi-detector computed tomography can detect vulnerable coronary artery plaque. Int. J. Cardiovasc. Imaging 26 (Suppl. 2), 245–252 (2010).

    PubMed  Google Scholar 

  56. Kitagawa, T. et al. Characterization of noncalcified coronary plaques and identification of culprit lesions in patients with acute coronary syndrome by 64-slice computed tomography. JACC Cardiovasc. Imaging 2, 153–160 (2009).

    PubMed  Google Scholar 

  57. Nakazawa, G. et al. Efficacy of culprit plaque assessment by 64-slice multidetector computed tomography to predict transient no-reflow phenomenon during percutaneous coronary intervention. Am. Heart J. 155, 1150–1157 (2008).

    PubMed  Google Scholar 

  58. Kodama, T., Kondo, T., Oida, A., Fujimoto, S. & Narula, J. Computed tomographic angiography-verified plaque characteristics and slow-flow phenomenon during percutaneous coronary intervention. JACC Cardiovasc. Interv. 5, 636–643 (2012).

    PubMed  Google Scholar 

  59. Tanaka, A. et al. Non-invasive assessment of plaque rupture by 64-slice multidetector computed tomography--comparison with intravascular ultrasound. Circ. J. 72, 1276–1281 (2008).

    PubMed  Google Scholar 

  60. Maurovich-Horvat, P. et al. The napkin-ring sign: CT signature of high risk coronary plaques? JACC Cardiovasc. Imaging 3, 440–444 (2010).

    PubMed  Google Scholar 

  61. Maurovich-Horvat, P. et al. The napkin-ring sign indicates advanced atherosclerotic lesions in coronary CT angiography. JACC Cardiovasc. Imaging 5, 1243–1252 (2012).

    PubMed  Google Scholar 

  62. Seifarth, H. et al. Histopathological correlates of the napkin-ring sign plaque in coronary CT angiography. Atherosclerosis 224, 90–96 (2012).

    CAS  PubMed  Google Scholar 

  63. Yamamoto, H., Kitagawa, T. & Kihara, Y. Dose napkin-ring sign suggest possibility to identify rupture-prone plaque in coronary computed tomography angiography? J. Cardiol. 62, 328–329 (2013).

    PubMed  Google Scholar 

  64. Otsuka, K. et al. Napkin-ring sign on coronary CT angiography for the prediction of acute coronary syndrome. JACC Cardiovasc. Imaging 6, 448–457 (2013).

    PubMed  Google Scholar 

  65. 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).

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  67. Achenbach, S. et al. Assessment of coronary remodeling in stenotic and nonstenotic coronary atherosclerotic lesions by multidetector spiral computed tomography. J. Am. Coll. Cardiol. 43, 842–847 (2004).

    PubMed  Google Scholar 

  68. Gauss, S. et al. Assessment of coronary artery remodelling by dual-source CT: a head-to-head comparison with intravascular ultrasound. Heart 97, 991–997 (2011).

    PubMed  Google Scholar 

  69. Moselewski, F. et al. Comparison of measurement of cross-sectional coronary atherosclerotic plaque and vessel areas by 16-slice multidetector computed tomography versus intravascular ultrasound. Am. J. Cardiol. 94, 1294–1297 (2004).

    PubMed  Google Scholar 

  70. Mintz, G. S. et al. American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS). A report of the American College of Cardiology Task Force on clinical expert consensus documents. J. Am. Coll. Cardiol. 37, 1478–1492 (2001).

    CAS  PubMed  Google Scholar 

  71. Kröner, E. S. et al. Positive remodeling on coronary computed tomography as a marker for plaque vulnerability on virtual histology intravascular ultrasound. Am. J. Cardiol. 107, 1725–1729 (2011).

    PubMed  Google Scholar 

  72. Otsuka, F., Finn, A. V. & Virmani, R. Do vulnerable and ruptured plaques hide in heavily calcified arteries? Atherosclerosis 229, 34–37 (2013).

    CAS  PubMed  Google Scholar 

  73. Greenland, P., LaBree, L., Azen, S. P., Doherty, T. M. & Detrano, R. C. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA 291, 210–215 (2004).

    CAS  PubMed  Google Scholar 

  74. Taylor, A. J. et al. Coronary calcium independently predicts incident premature coronary heart disease over measured cardiovascular risk factors: mean three-year outcomes in the Prospective Army Coronary Calcium (PACC) project. J. Am. Coll. Cardiol. 46, 807–814 (2005).

    CAS  PubMed  Google Scholar 

  75. Huang, H. et al. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation 103, 1051–1056 (2001).

    CAS  PubMed  Google Scholar 

  76. Maldonado, N. et al. A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture. Am. J. Physiol. Heart Circ. Physiol. 303, H619–H628 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Mauriello, A. et al. Coronary calcification identifies the vulnerable patient rather than the vulnerable plaque. Atherosclerosis 229, 124–129 (2013).

    CAS  PubMed  Google Scholar 

  78. Burke, A. P. et al. Pathophysiology of calcium deposition in coronary arteries. Herz 26, 239–244 (2001).

    CAS  PubMed  Google Scholar 

  79. Kataoka, Y. et al. Spotty calcification as a marker of accelerated progression of coronary atherosclerosis: insights from serial intravascular ultrasound. J. Am. Coll. Cardiol. 59, 1592–1597 (2012).

    PubMed  Google Scholar 

  80. Ehara, S. et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation 110, 3424–3429 (2004).

    PubMed  Google Scholar 

  81. van Velzen, J. E. 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. 18, 893–903 (2011).

    PubMed  PubMed Central  Google Scholar 

  82. Joshi, N. V. et al. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet 383, 705–713 (2014).

    PubMed  Google Scholar 

  83. Caro, C. G., Fitz-Gerald, J. M. & Schroter, R. C. Arterial wall shear and distribution of early atheroma in man. Nature 223, 1159–1160 (1969).

    CAS  PubMed  Google Scholar 

  84. Friedman, M. H., Bargeron, C. B., Deters, O. J., Hutchins, G. M. & Mark, F. F. Correlation between wall shear and intimal thickness at a coronary artery branch. Atherosclerosis 68, 27–33 (1987).

    CAS  PubMed  Google Scholar 

  85. 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).

    PubMed  PubMed Central  Google Scholar 

  86. Malek, A. M., Alper, S. L. & Izumo, S. Hemodynamic shear stress and its role in atherosclerosis. JAMA 282, 2035–2042 (1999).

    CAS  PubMed  Google Scholar 

  87. Wentzel, J. J. et al. Endothelial shear stress in the evolution of coronary atherosclerotic plaque and vascular remodelling: current understanding and remaining questions. Cardiovasc. Res. 96, 234–243 (2012).

    CAS  PubMed  Google Scholar 

  88. Chatzizisis, Y. S. et al. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J. Am. Coll. Cardiol. 49, 2379–2393 (2007).

    CAS  PubMed  Google Scholar 

  89. Slager, C. J. et al. The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications. Nat. Clin. Pract. Cardiovasc. Med. 2, 456–464 (2005).

    CAS  PubMed  Google Scholar 

  90. Samady, H. et al. Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation 124, 779–788 (2011).

    CAS  PubMed  Google Scholar 

  91. Fukumoto, Y. et al. Localized elevation of shear stress is related to coronary plaque rupture: a 3-dimensional intravascular ultrasound study with in-vivo color mapping of shear stress distribution. J. Am. Coll. Cardiol. 51, 645–650 (2008).

    PubMed  Google Scholar 

  92. Falk, E., Shah, P. K. & Fuster, V. Coronary plaque disruption. Circulation 92, 657–671 (1995).

    CAS  PubMed  Google Scholar 

  93. Puri, R., Nicholls, S. J., Ellis, S. G., Tuzcu, E. M. & Kapadia, S. R. High-risk coronary atheroma: the interplay between ischemia, plaque burden, and disease progression. J. Am. Coll. Cardiol. 63, 1134–1140 (2014).

    PubMed  Google Scholar 

  94. Hachamovitch, R. et al. Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation 97, 535–543 (1998).

    CAS  PubMed  Google Scholar 

  95. Shaw, L. J. et al. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 117, 1283–1291 (2008).

    PubMed  Google Scholar 

  96. Fearon, W. F. Is a myocardial infarction more likely to result from a mild coronary lesion or an ischemia-producing one? Circ. Cardiovasc. Interv. 4, 539–541 (2011).

    PubMed  Google Scholar 

  97. Fihn, S. D. et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J. Am. Coll. Cardiol. 60, e44–e164 (2012).

    PubMed  Google Scholar 

  98. Kim, H. J. et al. Patient-specific modeling of blood flow and pressure in human coronary arteries. Ann. Biomed. Eng. 38, 3195–3209 (2010).

    CAS  PubMed  Google Scholar 

  99. Taylor, C. A., Fonte, T. A. & Min, J. K. Computational fluid dynamics applied to cardiac computed tomography for noninvasive quantification of fractional flow reserve: scientific basis. J. Am. Coll. Cardiol. 61, 2233–2241 (2013).

    PubMed  Google Scholar 

  100. Nieman, K. & de Feijter, P. J. Aerodynamics in cardiac CT. Circ. Cardiovasc. Imaging 6, 853–854 (2013).

    PubMed  Google Scholar 

  101. Ramkumar, P. G., Mitsouras, D., Feldman, C. L., Stone, P. H. & Rybicki, F. J. New advances in cardiac computed tomography. Curr. Opin. Cardiol. 24, 596–603 (2009).

    PubMed  Google Scholar 

  102. Slager, C. J. et al. The role of shear stress in the generation of rupture-prone vulnerable plaques. Nat. Clin. Pract Cardiovasc. Med. 2, 401–407 (2005).

    CAS  PubMed  Google Scholar 

  103. Gimbrone, M. A. Jr, Topper, J. N., Nagel, T., Anderson, K. R. & Garcia-Cardena, G. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann. N Y Acad. Sci. 902, 230–239 (2000).

    CAS  PubMed  Google Scholar 

  104. Brooks, A. R., Lelkes, P. I. & Rubanyi, G. M. Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol. Genomics 9, 27–41 (2002).

    CAS  PubMed  Google Scholar 

  105. Chatzizisis, Y. S. et al. Augmented expression and activity of extracellular matrix-degrading enzymes in regions of low endothelial shear stress colocalize with coronary atheromata with thin fibrous caps in pigs. Circulation 123, 621–630 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Koskinas, K. C. et al. Synergistic effect of local endothelial shear stress and systemic hypercholesterolemia on coronary atherosclerotic plaque progression and composition in pigs. Int. J. Cardiol. 169, 394–401 (2013).

    PubMed  PubMed Central  Google Scholar 

  107. Stone, P. H. et al. Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study. Circulation 126, 172–181 (2012).

    PubMed  Google Scholar 

  108. Frauenfelder, T. et al. In-vivo flow simulation in coronary arteries based on computed tomography datasets: feasibility and initial results. Eur. Radiol. 17, 1291–1300 (2007).

    PubMed  Google Scholar 

  109. Jin, S. et al. Flow patterns and wall shear stress distributions at atherosclerotic-prone sites in a human left coronary artery--an exploration using combined methods of CT and computational fluid dynamics. Conf. Proc. IEEE Eng. Med. Biol. Soc. 5, 3789–3791 (2004).

    PubMed Central  Google Scholar 

  110. Borkin, M. A. et al. Evaluation of artery visualizations for heart disease diagnosis. IEEE Trans. Vis. Comput. Graph. 17, 2479–2488 (2011).

    PubMed  Google Scholar 

  111. Gijsen, F. J. et al. 3D reconstruction techniques of human coronary bifurcations for shear stress computations. J. Biomech. 47, 39–43 (2014).

    PubMed  Google Scholar 

  112. Rikhtegar, F. et al. Choosing the optimal wall shear parameter for the prediction of plaque location-A patient-specific computational study in human left coronary arteries. Atherosclerosis 221, 432–437 (2012).

    CAS  PubMed  Google Scholar 

  113. Bech, G. J. et al. Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: a randomized trial. Circulation 103, 2928–2934 (2001).

    CAS  PubMed  Google Scholar 

  114. Gijsen, F. J. et al. Strain distribution over plaques in human coronary arteries relates to shear stress. Am. J. Physiol. Heart Circ. Physiol. 295, H1608–H1614 (2008).

    CAS  PubMed  Google Scholar 

  115. Yong, A. S. et al. Intracoronary shear-related up-regulation of platelet P-selectin and platelet-monocyte aggregation despite the use of aspirin and clopidogrel. Blood 117, 11–20 (2011).

    CAS  PubMed  Google Scholar 

  116. Versteeg, D. 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 94, 770–776 (2008).

    CAS  PubMed  Google Scholar 

  117. Shmilovich, H. et al. Vulnerable plaque features on coronary CT angiography as markers of inducible regional myocardial hypoperfusion from severe coronary artery stenoses. Atherosclerosis 219, 588–595 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Muller, O. et al. Long-term follow-up after fractional flow reserve-guided treatment strategy in patients with an isolated proximal left anterior descending coronary artery stenosis. JACC Cardiovasc. Interv. 4, 1175–1182 (2011).

    PubMed  Google Scholar 

  119. Koo, B. K. et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J. Am. Coll. Cardiol. 58, 1989–1997 (2011).

    PubMed  Google Scholar 

  120. Min, J. K. et al. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA 308, 1237–1245 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Kim, K. H. et al. A novel noninvasive technology for treatment planning using virtual coronary stenting and computed tomography-derived computed fractional flow reserve. JACC Cardiovasc. Interv. 7, 72–78 (2014).

    PubMed  Google Scholar 

  122. US National Library of Medicine. Clinicaltrials.gov [online], (2014).

  123. Narula, J. Are we up to speed?: from big data to rich insights in CV imaging for a hyperconnected world. JACC Cardiovasc. Imaging 6, 1222–1224 (2013).

    PubMed  Google Scholar 

  124. Joshi, P. H. et al. A peripheral blood gene expression score is associated with plaque volume and phenotype by intravascular ultrasound with radiofrequency backscatter analysis: results from the ATLANTA study. Cardiovasc. Diagn. Ther. 3, 5–14 (2013).

    PubMed  PubMed Central  Google Scholar 

  125. Voros, S. et al. Apoprotein B, small-dense LDL and impaired HDL remodeling is associated with larger plaque burden and more noncalcified plaque as assessed by coronary CT angiography and intravascular ultrasound with radiofrequency backscatter: results from the ATLANTA I study. J. Am. Heart Assoc. 2, e000344 (2013).

    PubMed  PubMed Central  Google Scholar 

  126. Hyafil, F. et al. Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography. Nat. Med. 13, 636–641 (2007).

    CAS  PubMed  Google Scholar 

  127. Cormode, D. P. et al. Atherosclerotic plaque composition: analysis with multicolor CT and targeted gold nanoparticles. Radiology 256, 774–782 (2010).

    PubMed  PubMed Central  Google Scholar 

  128. Rogers, I. S. et al. Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. JACC Cardiovasc. Imaging 3, 388–397 (2010).

    PubMed  Google Scholar 

Download references

Acknowledgements

P.M-H. acknowledges support from the European Union, State of Hungary, and European Social Fund in the framework of TÁMOP 4.2.4. A/1-11-1-2012-0001 'National Excellence Program'. M.F. acknowledges support from the American Heart Association (grant number: 13FTF16450001).

Author information

Authors and Affiliations

Authors

Contributions

The authors contributed equally to researching data for the article, discussion of content, writing, reviewing, and editing of the manuscript before submission.

Corresponding author

Correspondence to Udo Hoffmann.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Morphologic computed tomography features of vulnerable plaques (DOCX 38 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maurovich-Horvat, P., Ferencik, M., Voros, S. et al. Comprehensive plaque assessment by coronary CT angiography. Nat Rev Cardiol 11, 390–402 (2014). https://doi.org/10.1038/nrcardio.2014.60

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2014.60

This article is cited by

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