MR Imaging of Vulnerable Carotid Atherosclerotic Plaques

  • Chin Lik Tan
  • Rohitashwa Sinha
  • Karol Budohoski
  • Rikin A. TrivediEmail author


Carotid artery atherosclerosis is a major cause of stroke. It has been traditionally thought that luminal stenosis secondary to the presence of atherosclerotic plaques reduces blood flow along the carotid arteries, leading to cerebral ischaemia and infarction. However, recent advances have shown that atherosclerotic plaques which carry a high risk of developing complications, i.e. ‘vulnerable plaques’, display certain features which can be identified by various imaging techniques. Specifically, a variety of MRI sequences and modalities have been employed to recognise characteristics of fibrous cap, lipid-rich necrotic core, inflammation and biomechanical stress. They have been shown to be linked to the disease progression of atherosclerotic plaques, as well as the improvement following treatment. This chapter reviews the use of MRI in the investigation of carotid artery disease and the identification of vulnerable atherosclerotic plaques.


MRI Carotid Atherosclerotic plaque 


  1. 1.
    Levy EI, Mocco J, Samuelson RM, Ecker RD, Jahromi BS, Hopkins LN. Optimal treatment of carotid artery disease. J Am Coll Cardiol. 2008;51:979–85.CrossRefPubMedGoogle Scholar
  2. 2.
    Fisher M. Occlusion of the internal carotid artery. AMA Arch Neurol Psychiatry. 1951;65:346–77.CrossRefPubMedGoogle Scholar
  3. 3.
    Rothwell PM, Eliasziw M, Gutnikov SA, Fox AJ, Taylor DW, Mayberg MR, Warlow CP, Barnett HJ. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet. 2003;361:107–16.CrossRefPubMedGoogle Scholar
  4. 4.
    Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995;273:1421–8.CrossRefGoogle Scholar
  5. 5.
    Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, Thomas D, MRC, Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004;363:1491–502.CrossRefPubMedGoogle Scholar
  6. 6.
    Halliday A, Harrison M, Hayter E, Kong X, Mansfield A, Marro J, Pan H, Peto R, Potter J, Rahimi K, Rau A, Robertson S, Streifler J, Thomas D, Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet. 2010;376:1074–84.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987;316:1371–5.CrossRefPubMedGoogle Scholar
  8. 8.
    Brown PB, Zwiebel WJ, Call GK. Degree of cervical carotid artery stenosis and hemispheric stroke: duplex US findings. Radiology. 1989;170:541–3.CrossRefPubMedGoogle Scholar
  9. 9.
    Stary HC, Chandler AB, Glagov S, Guyton JR, Insull Jr W, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1994;89:2462–78.CrossRefPubMedGoogle Scholar
  10. 10.
    Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull Jr W, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1995;92:1355–74.CrossRefPubMedGoogle Scholar
  11. 11.
    Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone PH, Waxman S, Raggi P, Madjid M, Zarrabi A, Burke A, Yuan C, Fitzgerald PJ, Siscovick DS, de Korte CL, Aikawa M, Airaksinen KE, Assmann G, Becker CR, Chesebro JH, Farb A, Galis ZS, Jackson C, Jang IK, Koenig W, Lodder RA, March K, Demirovic J, Navab M, Priori SG, Rekhter MD, Bahr R, Grundy SM, Mehran R, Colombo A, Boerwinkle E, Ballantyne C, Insull Jr W, Schwartz RS, Vogel R, Serruys PW, Hansson GK, Faxon DP, Kaul S, Drexler H, Greenland P, Muller JE, Virmani R, Ridker PM, Zipes DP, Shah PK, Willerson JT. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part II. Circulation. 2003;108:1772–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone PH, Waxman S, Raggi P, Madjid M, Zarrabi A, Burke A, Yuan C, Fitzgerald PJ, Siscovick DS, de Korte CL, Aikawa M, Juhani Airaksinen KE, Assmann G, Becker CR, Chesebro JH, Farb A, Galis ZS, Jackson C, Jang IK, Koenig W, Lodder RA, March K, Demirovic J, Navab M, Priori SG, Rekhter MD, Bahr R, Grundy SM, Mehran R, Colombo A, Boerwinkle E, Ballantyne C, Insull Jr W, Schwartz RS, Vogel R, Serruys PW, Hansson GK, Faxon DP, Kaul S, Drexler H, Greenland P, Muller JE, Virmani R, Ridker PM, Zipes DP, Shah PK, Willerson JT. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part I. Circulation. 2003;108:1664–72.CrossRefPubMedGoogle Scholar
  13. 13.
    Stemme S, Faber B, Holm J, Wiklund O, Witztum JL, Hansson GK. T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci U S A. 1995;92:3893–7.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Saam T, Hatsukami TS, Takaya N, Chu B, Underhill H, Kerwin WS, Cai J, Ferguson MS, Yuan C. The vulnerable, or high-risk, atherosclerotic plaque: noninvasive MR imaging for characterization and assessment. Radiology. 2007;244:64–77.CrossRefPubMedGoogle Scholar
  15. 15.
    Trivedi RA, Gillard JH, Kirkpatrick PJ. Modern methods for imaging carotid atheroma. Br J Neurosurg. 2008;22:350–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Yuan C, Zhang SX, Polissar NL, Echelard D, Ortiz G, Davis JW, Ellington E, Ferguson MS, Hatsukami TS. Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke. Circulation. 2002;105:181–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Sinha R, Budohoski KP, Young VEL, Trivedi RA. Magnetic resonance imaging of vulnerable carotid plaques. In: Saba L et al., editors. Multi-modality atherosclerosis imaging and diagnosis. New York: Springer; 2014. p. 107–19.CrossRefGoogle Scholar
  18. 18.
    Gupta A, Baradaran H, Schweitzer AD, Kamel H, Pandya A, Delgado D, Dunning A, Mushlin AI, Sanelli PC. Carotid plaque MRI and stroke risk: a systematic review and meta-analysis. Stroke. 2013;44:3071–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD, Lusis AJ. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation. 1995;91(9):2488–96.CrossRefPubMedGoogle Scholar
  20. 20.
    Saam T, Ferguson MS, Yarnykh VL, Takaya N, Xu D, Polissar NL, Hatsukami TS, Yuan C. Quantitative evaluation of carotid plaque composition by in vivo MRI. Arterioscler Thromb Vasc Biol. 2005;25:234–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Virmani R, Narula J, Farb A. When neoangiogenesis ricochets. Am Heart J. 1998;136:937–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Takaya N, Yuan C, Chu B, Saam T, Underhill H, Cai J, Tran N, Polissar NL, Isaac C, Ferguson MS, Garden GA, Cramer SC, Maravilla KR, Hashimoto B, Hatsukami TS. Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: a prospective assessment with MRI–initial results. Stroke. 2006;37:818–23.CrossRefPubMedGoogle Scholar
  23. 23.
    Hatsukami TS, Ross R, Polissar NL, Yuan C. Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging. Circulation. 2000;102:959–64.CrossRefPubMedGoogle Scholar
  24. 24.
    Trivedi RA, U-King-Im JM, Graves MJ, Horsley J, Goddard M, Kirkpatrick PJ, Gillard JH. MRI-derived measurements of fibrous-cap and lipid-core thickness: the potential for identifying vulnerable carotid plaques in vivo. Neuroradiology. 2004;46:738–43.CrossRefPubMedGoogle Scholar
  25. 25.
    Cai J, Hatsukami TS, Ferguson MS, Kerwin WS, Saam T, Chu B, Takaya N, Polissar NL, Yuan C. In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque: comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology. Circulation. 2005;112:3437–44.CrossRefPubMedGoogle Scholar
  26. 26.
    Ota H, Reeves MJ, Zhu DC, Majid A, Collar A, Yuan C, DeMarco JK. Sex differences of high-risk carotid atherosclerotic plaque with less than 50% stenosis in asymptomatic patients: an in vivo 3T MRI study. AJNR Am J Neuroradiol. 2013;34:1049–1055, S1.CrossRefPubMedGoogle Scholar
  27. 27.
    Yamaguchi M, Sasaki M, Ohba H, Mori K, Narumi S, Katsura N, Ohura K, Kudo K, Terayama Y. Quantitative assessment of changes in carotid plaques during cilostazol administration using three-dimensional ultrasonography and non-gated magnetic resonance plaque imaging. Neuroradiology. 2012;54:939–45.CrossRefPubMedGoogle Scholar
  28. 28.
    Chen W, Vucic E, Leupold E, Mulder WJ, Cormode DP, Briley-Saebo KC, Barazza A, Fisher EA, Dathe M, Fayad ZA. Incorporation of an apoE-derived lipopeptide in high-density lipoprotein MRI contrast agents for enhanced imaging of macrophages in atherosclerosis. Contrast Media Mol Imaging. 2008;3:233–42.CrossRefPubMedGoogle Scholar
  29. 29.
    Spagnoli LG, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, Schwartz RS, Piepgras DG, Pistolese R, Ippoliti A, Holmes Jr DR. Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA. 2004;292:1845–52.CrossRefPubMedGoogle Scholar
  30. 30.
    Huang Y, Teng Z, Sadat U, He J, Graves MJ, Gillard JH. In vivo MRI-based simulation of fatigue process: a possible trigger for human carotid atherosclerotic plaque rupture. Biomed Eng Online. 2013;12:36.PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Kwee RM, van Oostenbrugge RJ, Mess WH, Prins MH, van der Geest RJ, ter Berg JW, Franke CL, Korten AG, Meems BJ, van Engelshoven JM, Wildberger JE, Kooi ME. MRI of carotid atherosclerosis to identify TIA and stroke patients who are at risk of a recurrence. J Magn Reson Imaging. 2013;37:1189–94.CrossRefPubMedGoogle Scholar
  32. 32.
    Chu B, Ferguson MS, Underhill H, Takaya N, Cai J, Kliot M, Yuan C, Hatsukami TS. Images in cardiovascular medicine. Detection of carotid atherosclerotic plaque ulceration, calcification, and thrombosis by multicontrast weighted magnetic resonance imaging. Circulation. 2005;112(1):e3–4.CrossRefPubMedGoogle Scholar
  33. 33.
    Chu B, Yuan C, Takaya N, Shewchuk JR, Clowes AW, Hatsukami TS. Images in cardiovascular medicine. Serial high-spatial-resolution, multisequence magnetic resonance imaging studies identify fibrous cap rupture and penetrating ulcer into carotid atherosclerotic plaque. Circulation. 2006;113(12):e660–1.CrossRefPubMedGoogle Scholar
  34. 34.
    Yu W, Underhill HR, Ferguson MS, Hippe DS, Hatsukami TS, Yuan C, Chu B. The added value of longitudinal black-blood cardiovascular magnetic resonance angiography in the cross sectional identification of carotid atherosclerotic ulceration. J Cardiovasc Magn Reson. 2009;11:31.PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Zhao H, Zhao X, Liu X, Cao Y, Hippe DS, Sun J, Li F, Xu J, Yuan C. Association of carotid atherosclerotic plaque features with acute ischemic stroke: a magnetic resonance imaging study. Eur J Radiol. 2013;82:e465–70.PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Underhill HR, Hatsukami TS, Cai J, Yu W, DeMarco JK, Polissar NL, Ota H, Zhao X, Dong L, Oikawa M, Yuan C. A noninvasive imaging approach to assess plaque severity: the carotid atherosclerosis score. AJNR Am J Neuroradiol. 2010;31:1068–75.PubMedCentralCrossRefPubMedGoogle Scholar
  37. 37.
    Young VE, Patterson AJ, Sadat U, Bowden DJ, Graves MJ, Tang TY, Priest AN, Skepper JN, Kirkpatrick PJ, Gillard JH. Diffusion-weighted magnetic resonance imaging for the detection of lipid-rich necrotic core in carotid atheroma in vivo. Neuroradiology. 2010;52:929–36.CrossRefPubMedGoogle Scholar
  38. 38.
    Xu D, Hippe DS, Underhill HR, Oikawa-Wakayama M, Dong L, Yamada K, Yuan C, Hatsukami TS. Prediction of high-risk plaque development and plaque progression with the carotid atherosclerosis score. JACC Cardiovasc Imaging. 2014;7(4):366–73. pii: S1936-878X(13)00900-5.PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Zhao XQ, Dong L, Hatsukami T, Phan BA, Chu B, Moore A, Lane T, Neradilek MB, Polissar N, Monick D, Lee C, Underhill H, Yuan C. MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course. JACC Cardiovasc Imaging. 2011;4:977–86.PubMedCentralCrossRefPubMedGoogle Scholar
  40. 40.
    Sun J, Balu N, Hippe DS, Xue Y, Dong L, Zhao X, Li F, Xu D, Hatsukami TS, Yuan C. Subclinical carotid atherosclerosis: short-term natural history of lipid-rich necrotic core–a multicenter study with MR imaging. Radiology. 2013;268:61–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Corti R, Fayad ZA, Fuster V, Worthley SG, Helft G, Chesebro J, Mercuri M, Badimon JJ. Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a longitudinal study by high-resolution, noninvasive magnetic resonance imaging. Circulation. 2001;104:249–52.CrossRefPubMedGoogle Scholar
  42. 42.
    Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Smith D, Weinberger J, Wentzel J, Mizsei G, Mercuri M, Badimon JJ. Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years’ follow-up by high-resolution noninvasive magnetic resonance imaging. Circulation. 2002;106:2884–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Chaplin WF, Muntwyler J, Viles-Gonzalez JF, Weinberger J, Smith DA, Mizsei G, Badimon JJ. Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging. J Am Coll Cardiol. 2005;46:106–12.CrossRefPubMedGoogle Scholar
  44. 44.
    Migrino RQ, Bowers M, Harmann L, Prost R, LaDisa Jr JF. Carotid plaque regression following 6-month statin therapy assessed by 3T cardiovascular magnetic resonance: comparison with ultrasound intima media thickness. J Cardiovasc Magn Reson. 2011;13:37.PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Fayad ZA, Mani V, Woodward M, Kallend D, Abt M, Burgess T, Fuster V, Ballantyne CM, Stein EA, Tardif JC, Rudd JH, Farkouh ME, Tawakol A. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet. 2011;378:1547–59.PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Bianda N, Di Valentino M, Periat D, Segatto JM, Oberson M, Moccetti M, Sudano I, Santini P, Limoni C, Froio A, Stuber M, Corti R, Gallino A, Wyttenbach R. Progression of human carotid and femoral atherosclerosis: a prospective follow-up study by magnetic resonance vessel wall imaging. Eur Heart J. 2012;33:230–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Millon A, Mathevet JL, Boussel L, Faries PL, Fayad ZA, Douek PC, Feugier P. High-resolution magnetic resonance imaging of carotid atherosclerosis identifies vulnerable carotid plaques. J Vasc Surg. 2013;57:1046–1051.e2.CrossRefPubMedGoogle Scholar
  48. 48.
    Hosseini AA, Kandiyil N, Macsweeney ST, Altaf N, Auer DP. Carotid plaque hemorrhage on magnetic resonance imaging strongly predicts recurrent ischemia and stroke. Ann Neurol. 2013;73:774–84.PubMedCentralCrossRefPubMedGoogle Scholar
  49. 49.
    Sun J, Underhill HR, Hippe DS, Xue Y, Yuan C, Hatsukami TS. Sustained acceleration in carotid atherosclerotic plaque progression with intraplaque hemorrhage: a long-term time course study. JACC Cardiovasc Imaging. 2012;5:798–804.PubMedCentralCrossRefPubMedGoogle Scholar
  50. 50.
    Qiao Y, Hallock KJ, Hamilton JA. Magnetization transfer magnetic resonance of human atherosclerotic plaques ex vivo detects areas of high protein density. J Cardiovasc Magn Reson. 2011;13:73.PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Kampschulte A, Ferguson MS, Kerwin WS, Polissar NL, Chu B, Saam T, Hatsukami TS, Yuan C. Differentiation of intraplaque versus juxtaluminal hemorrhage/thrombus in advanced human carotid atherosclerotic lesions by in vivo magnetic resonance imaging. Circulation. 2004;110:3239–44.CrossRefPubMedGoogle Scholar
  52. 52.
    Kandiyil N, Altaf N, Hosseini AA, MacSweeney ST, Auer DP. Lower prevalence of carotid plaque hemorrhage in women, and its mediator effect on sex differences in recurrent cerebrovascular events. PLoS One. 2012;7, e47319.PubMedCentralCrossRefPubMedGoogle Scholar
  53. 53.
    Ota H, Yarnykh VL, Ferguson MS, Underhill HR, Demarco JK, Zhu DC, Oikawa M, Dong L, Zhao X, Collar A, Hatsukami TS, Yuan C. Carotid intraplaque hemorrhage imaging at 3.0-T MR imaging: comparison of the diagnostic performance of three T1-weighted sequences. Radiology. 2010;254:551–63.PubMedCentralCrossRefPubMedGoogle Scholar
  54. 54.
    Wang J, Ferguson MS, Balu N, Yuan C, Hatsukami TS, Bornert P. Improved carotid intraplaque hemorrhage imaging using a slab-selective phase-sensitive inversion-recovery (SPI) sequence. Magn Reson Med. 2010;64:1332–40.CrossRefPubMedGoogle Scholar
  55. 55.
    Frostegård J. Immunity, atherosclerosis and cardiovascular disease. BMC Med. 2013;11:117.PubMedCentralCrossRefPubMedGoogle Scholar
  56. 56.
    Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32:2045–51.PubMedCentralCrossRefPubMedGoogle Scholar
  57. 57.
    Schmitz SA, Coupland SE, Gust R, Winterhalter S, Wagner S, Kresse M, Semmler W, Wolf KJ. Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits. Invest Radiol. 2000;35:460–71.CrossRefPubMedGoogle Scholar
  58. 58.
    Schmitz SA, Taupitz M, Wagner S, Wolf KJ, Beyersdorff D, Hamm B. Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles. J Magn Reson Imaging. 2001;14:355–61.CrossRefPubMedGoogle Scholar
  59. 59.
    Kooi ME, Cappendijk VC, Cleutjens KB, Kessels AG, Kitslaar PJ, Borgers M, Frederik PM, Daemen MJ, van Engelshoven JM. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation. 2003;107:2453–8.CrossRefPubMedGoogle Scholar
  60. 60.
    Trivedi RA, U-King-Im JM, Graves MJ, Cross JJ, Horsley J, Goddard MJ, Skepper JN, Quartey G, Warburton E, Joubert I, Wang L, Kirkpatrick PJ, Brown J, Gillard JH. In vivo detection of macrophages in human carotid atheroma: temporal dependence of ultrasmall superparamagnetic particles of iron oxide-enhanced MRI. Stroke. 2004;35:1631–5.CrossRefPubMedGoogle Scholar
  61. 61.
    Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, U-King-Im JM, Li ZY, Walsh SR, Brown AP, Kirkpatrick PJ, Warburton EA, Hayes PD, Varty K, Boyle JR, Gaunt ME, Zalewski A, Gillard JH. The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. J Am Coll Cardiol. 2009;53:2039–50.CrossRefPubMedGoogle Scholar
  62. 62.
    Tang TY, Howarth SP, Li ZY, Miller SR, Graves MJ, U-King-Im JM, Trivedi RA, Walsh SR, Brown AP, Kirkpatrick PJ, Gaunt ME, Gillard JH. Correlation of carotid atheromatous plaque inflammation with biomechanical stress: utility of USPIO enhanced MR imaging and finite element analysis. Atherosclerosis. 2008;196:879–87.CrossRefPubMedGoogle Scholar
  63. 63.
    Tang TY, Howarth SP, Miller SR, Graves MJ, U-King-Im JM, Li ZY, Walsh SR, Patterson AJ, Kirkpatrick PJ, Warburton EA, Varty K, Gaunt ME, Gillard JH. Correlation of carotid atheromatous plaque inflammation using USPIO-enhanced MR imaging with degree of luminal stenosis. Stroke. 2008;39:2144–7.CrossRefPubMedGoogle Scholar
  64. 64.
    Altaf N, Akwei S, Auer DP, MacSweeney ST, Lowe J. Magnetic resonance detected carotid plaque hemorrhage is associated with inflammatory features in symptomatic carotid plaques. Ann Vasc Surg. 2013;27:655–61.CrossRefPubMedGoogle Scholar
  65. 65.
    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;88:945–50.CrossRefPubMedGoogle Scholar
  66. 66.
    Moreno PR, Purushothaman KR, Fuster V, Echeverri D, Truszczynska H, Sharma SK, Badimon JJ, O’Connor WN. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation. 2004;110:2032–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Aoki S, Aoki K, Ohsawa S, Nakajima H, Kumagai H, Araki T. Dynamic MR imaging of the carotid wall. J Magn Reson Imaging. 1999;9:420–7.CrossRefPubMedGoogle Scholar
  68. 68.
    Aoki S, Nakajima H, Kumagai H, Araki T. Dynamic contrast-enhanced MR angiography and MR imaging of the carotid artery: high-resolution sequences in different acquisition planes. AJNR Am J Neuroradiol. 2000;21(2):381–5.PubMedGoogle Scholar
  69. 69.
    Kerwin W, Hooker A, Spilker M, Vicini P, Ferguson M, Hatsukami T, Yuan C. Quantitative magnetic resonance imaging analysis of neovasculature volume in carotid atherosclerotic plaque. Circulation. 2003;107:851–6.CrossRefPubMedGoogle Scholar
  70. 70.
    Kerwin WS, O’Brien KD, Ferguson MS, Polissar N, Hatsukami TS, Yuan C. Inflammation in carotid atherosclerotic plaque: a dynamic contrast-enhanced MR imaging study. Radiology. 2006;241:459–68.PubMedCentralCrossRefPubMedGoogle Scholar
  71. 71.
    Briley-Saebo KC, Shaw PX, Mulder WJ, Choi SH, Vucic E, Aguinaldo JG, Witztum JL, Fuster V, Tsimikas S, Fayad ZA. Targeted molecular probes for imaging atherosclerotic lesions with magnetic resonance using antibodies that recognize oxidation-specific epitopes. Circulation. 2008;117:3206–15.PubMedCentralCrossRefPubMedGoogle Scholar
  72. 72.
    Spuentrup E, Botnar RM, Wiethoff AJ, Ibrahim T, Kelle S, Katoh M, Ozgun M, Nagel E, Vymazal J, Graham PB, Gunther RW, Maintz D. MR imaging of thrombi using EP-2104R, a fibrin-specific contrast agent: initial results in patients. Eur Radiol. 2008;18:1995–2005.CrossRefPubMedGoogle Scholar
  73. 73.
    Laitinen I, Saraste A, Weidl E, Poethko T, Weber AW, Nekolla SG, Leppanen P, Yla-Herttuala S, Holzlwimmer G, Walch A, Esposito I, Wester HJ, Knuuti J, Schwaiger M. Evaluation of alphavbeta3 integrin-targeted positron emission tomography tracer 18F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice. Circ Cardiovasc Imaging. 2009;2:331–8.CrossRefPubMedGoogle Scholar
  74. 74.
    Mulder WJ, Strijkers GJ, Briley-Saboe KC, Frias JC, Aguinaldo JG, Vucic E, Amirbekian V, Tang C, Chin PT, Nicolay K, Fayad ZA. Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG-micelles. Magn Reson Med. 2007;58:1164–70.CrossRefPubMedGoogle Scholar
  75. 75.
    Nahrendorf M, Jaffer FA, Kelly KA, Sosnovik DE, Aikawa E, Libby P, Weissleder R. Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation. 2006;114:1504–11.CrossRefPubMedGoogle Scholar
  76. 76.
    Lancelot E, Amirbekian V, Brigger I, Raynaud JS, Ballet S, David C, Rousseaux O, Le Greneur S, Port M, Lijnen HR, Bruneval P, Michel JB, Ouimet T, Roques B, Amirbekian S, Hyafil F, Vucic E, Aguinaldo JG, Corot C, Fayad ZA. Evaluation of matrix metalloproteinases in atherosclerosis using a novel noninvasive imaging approach. Arterioscler Thromb Vasc Biol. 2008;28:425–32.CrossRefPubMedGoogle Scholar
  77. 77.
    Millon A, Boussel L, Brevet M, Mathevet JL, Canet-Soulas E, Mory C, Scoazec JY, Douek P. Clinical and histological significance of gadolinium enhancement in carotid atherosclerotic plaque. Stroke. 2012;43:3023–8.CrossRefPubMedGoogle Scholar
  78. 78.
    Teng Z, He J, Degnan AJ, Chen S, Sadat U, Bahaei NS, Rudd JH, Gillard JH. Critical mechanical conditions around neovessels in carotid atherosclerotic plaque may promote intraplaque hemorrhage. Atherosclerosis. 2012;223:321–6.PubMedCentralCrossRefPubMedGoogle Scholar
  79. 79.
    Kaazempur-Mofrad MR, Isasi AG, Younis HF, Chan RC, Hinton DP, Sukhova G, LaMuraglia GM, Lee RT, Kamm RD. Characterization of the atherosclerotic carotid bifurcation using MRI, finite element modeling, and histology. Ann Biomed Eng. 2004;32:932–46.CrossRefPubMedGoogle Scholar
  80. 80.
    Selwaness M, van Den Bouwhuijsen Q, Mattace-Raso FU, Verwoert GC, Hofman A, Franco OH, Witteman JC, van der Lugt A, Vernooij MW, Wentzel JJ. Arterial stiffness is associated with carotid intraplaque hemorrhage in the general population: The Rotterdam Study. Arterioscler Thromb Vasc Biol. 2014;34(4):927–32.CrossRefPubMedGoogle Scholar
  81. 81.
    Trivedi RA, Li ZY, U-King-Im J, Graves MJ, Kirkpatrick PJ, Gillard JH. Identifying vulnerable carotid plaques in vivo using high resolution magnetic resonance imaging-based finite element analysis. J Neurosurg. 2007;107:536–42.CrossRefPubMedGoogle Scholar
  82. 82.
    Huang X, Teng Z, Canton G, Ferguson M, Yuan C, Tang D. Intraplaque hemorrhage is associated with higher structural stresses in human atherosclerotic plaques: an in vivo MRI-based 3D fluid-structure interaction study. Biomed Eng Online. 2010;9:86.PubMedCentralCrossRefPubMedGoogle Scholar
  83. 83.
    Sadat U, Teng Z, Young VE, Li ZY, Gillard JH. Utility of magnetic resonance imaging-based finite element analysis for the biomechanical stress analysis of hemorrhagic and non-hemorrhagic carotid plaques. Circ J. 2011;75:884–9.CrossRefPubMedGoogle Scholar
  84. 84.
    Canton G, Hippe DS, Sun J, Underhill HR, Kerwin WS, Tang D, Yuan C. Characterization of distensibility, plaque burden, and composition of the atherosclerotic carotid artery using magnetic resonance imaging. Med Phys. 2012;39:6247–53.PubMedCentralCrossRefPubMedGoogle Scholar
  85. 85.
    Li ZY, Tang TY, Jiang F, Zhang Y, Gillard JH. Reduction in arterial wall strain with aggressive lipid-lowering therapy in patients with carotid artery disease. Circ J. 2011;75:1486–92.CrossRefPubMedGoogle Scholar
  86. 86.
    Sadat U, Howarth SP, Usman A, Taviani V, Tang TY, Graves MJ, Gillard JH. Effect of low-and high-dose atorvastatin on carotid artery distensibility using carotid magnetic resonance imaging -a post-hoc sub group analysis of ATHEROMA (Atorvastatin Therapy: Effects On Reduction Of Macrophage Activity) Study. J Atheroscler Thromb. 2013;20(1):46–56.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Chin Lik Tan
    • 1
  • Rohitashwa Sinha
    • 1
  • Karol Budohoski
    • 1
  • Rikin A. Trivedi
    • 1
    Email author
  1. 1.Department of NeurosurgeryAddenbrooke’s HospitalCambridgeUK

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