The vulnerable coronary plaque: update on imaging technologies

Summary

Several studies have been carried out on vulnerable plaque as the main culprit for ischaemic cardiac events. Historically, the most important diagnostic technique for studying coronary atherosclerotic disease was to determine the residual luminal diameter by angiographic measurement of the stenosis. However, it has become clear that vulnerable plaque rupture as well as thrombosis, rather than stenosis, triggers most acute ischaemic events and that the quantification of risk based merely on severity of the arterial stenosis is not sufficient. In the last decades, substantial progresses have been made on optimisation of techniques detecting the arterial wall morphology, plaque composition and inflammation. To date, the use of a single technique is not recommended to precisely identify the progression of the atherosclerotic process in human beings. In contrast, the integration of data that can be derived from multiple methods might improve our knowledge about plaque destabilisation. The aim of this narrative review is to update evidence on the accuracy of the currently available non-invasive and invasive imaging techniques in identifying components and morphologic characteristics associated with coronary plaque vulnerability.

Keywords

Vulnerable plaque - atherosclerosis - imaging - nuclear medicine - coronary arteries

• References

• 1 Brevoord D. et al. Remote ischaemic conditioning to protect against ischaemia-reperfusion injury: a systematic review and meta-analysis. PLoS One 2012; 7: e42179.
• 2 Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation 2005; 111: 3481-3488.
• 3 Falk E. et al. Coronary plaque disruption. Circulation 1995; 92: 657-671.
• 4 Moreno PR. et al. Promoting mechanisms of vascular health: circulating progenitor cells, angiogenesis, and reverse cholesterol transport. J Ann Coll Cardiol 2009; 53: 2315-2323.
• 5 Schaar JA. et al. Terminology for high risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque. June 17 and 18, 2003, Santorini, Greece. Eur Heart J 2004; 25: 1077-1082.
• 6 Loree HM. et al. Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. Circ Res 1992; 71: 850-858.
• 7 Richardson PD. et al. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989; 2: 941-944.
• 8 Cheng GC. et al. Distribution of circumferential stress in ruptured and stable atherosclerotic lesions: a structural analysis with histopathological correlation. Circulation 1993; 87: 1179-1187.
• 9 Naghavi M. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003; 108: 1772-1778.
• 10 Zethelius B. et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Eng J Med 2008; 358: 2107-2116.
• 11 Shaub N. et al. Markers of plaque instability in the early diagnosis and risk stratification of acute myocardial infarction. Clin Chem 2012; 58: 246-256.
• 12 Ferroni P. et al. Biomarkers of platelet activation in acute coronary syndromes. Thromb Haemost 2012; 108: 1109-1123.
• 13 Flierl U, Schafer A. Fractalkine - a local inflammatory marker aggravating platelet activation at the vulnerable plaque. Thromb Haemost 2012; 108: 457-463.
• 14 Alsheikh-Ali AA. et al. The vulnerable atherosclerotic plaque: scope of the literature. Ann Intern Med 2010; 153: 387-395.
• 15 Naghavi M. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 2003; 108: 1664-1672.
• 16 Muller JE. et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Eng J Med 1985; 313: 1315-1322.
• 17 Kolodgie FD. et al. Pathologic assessment of the vulnerable human coronary plaque. Heart 2004; 90: 1385-1391.
• 18 Virmani R. et al. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006; 47: C13-C18.
• 19 Narula J. et al. Arithmetic of vulnerable plaques for noninvasive imaging. Nat Clin Pract Cardiovasc Med 2008; 5: s2-s10.
• 20 Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol 2006; 47: C7-C12.
• 21 Yla-Herttuala. et al. Stabilisation of atherosclerotic plaques. Thromb Haemost 2011; 106: 1-19.
• 22 Loree HM. et al. Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. Circ Res 1992; 71: 850-858.
• 23 Schaar JA. et al. Intravascular palpography for vulnerable plaque assessment. J Am Coll Cardiol 2006; 47: C86-C91.
• 24 Moreno PR. Vulnerable plaque: definition, diagnosis and teatment. Clin Cardiol 2010; 28: 1-30.
• 25 Davies MJ. The pathophysiology of acute coronary syndromes. Heart 2000; 83: 361-366.
• 26 Felton CV. et al. Relation of plaque lipid composition and morphology to the stability of human aortic plaques. Aterioscler Thromb Vasc Biol 1997; 17: 1337-1345.
• 27 Fuster V. et al. Atherothrombosis and high-risk plaque part I: evolving concepts. J Am Coll Cardiol 2005; 46: 937-954.
• 28 Waxman S. et al. Detection and treatment of vulnerable plaques and vulnerable patients: novel approaches to prevention of coronary events. Circulation 2006; 114: 2390-2411.
• 29 Kockx MM. et al. Phagocytosis and macrophage activationassociated with hemorrhagic microvessels in human atherosclerosis. Atherioscler Thromb Vasc Biol 2003; 23: 440-446.
• 30 Kolodgie FD. et al. Intraplaque Hemorrhage and progression of coronary atheroma. N Eng J Med 2003; 349: 2316-2325.
• 31 Michel JB. et al. Intraplaque Hemorrhages as the trigger of plaque vulnerability. Eur Heart J 2011; 32: 1977-1985.
• 32 Arbustini E. et al. Plaque composition in plexogenic and thromboembolic pulmonary hypertension: the critical role of thrombotic material in pultaceous core formation. Heart 2002; 88: 177-182.
• 33 Moreno PR. et al. Intimomedial interface damage and adventitial inflammation interface damage and adventitial inflammation is increased beneath disrupted atherosclerosis in the aorta: implications for plaque vulnerability. Circulation 2002; 105: 2504-2511.
• 34 Tronc F. et al. Role of matrix metalloproteinases in blood flow-induced arterial enlargement: interaction with NO. Arterioscler Thromb Vasc Biol 2000; 20: E120-E126.
• 35 Bruke AP. et al. Morphological predictors of arterial remodelling in coronary atherosclerosis. Circulation 2002; 105: 297-303.
• 36 Stone GW. et al. for the PROSPECT Investigators. A prospective natural-history study of coronary atherosclerosis. N Engl J Med 2011; 364: 226-235.
• 37 Corti R. et al. New understanding of atherosclerosis (Clinically and experimentally) with evolving MRI technologies in vivo. Ann NY Acad Sci 2001; 947: 181-195.
• 38 Achenbach S. et al. Detection of coronary artery stenoses by contrast-enhanced, retrospectively electrocardiographically gated, multislice spiral computed tomography. Circulation 2001; 103: 2535-2538.
• 39 Leschka S. et al. Optimal image reconstruction intervals for non-invasive coronary angiography wit 64-slice CT. Eur Radiol 2006; 16: 1964-1972.
• 40 Vanhoenacker PK. et al. Diagnostic performance of multidetector CT angiography for assessment of coronary artery disease: meta-analysis. Radiology 2007; 244: 419-428.
• 41 Kido T. et al. Cardiac imaging using 256-detector row four dimensional CT: preliminary clinical report. Radiat Med 2007; 25: 38-44.
• 42 Hendel RC. et al. ACCF/ACR/SCCT, SCMR, ASNC, NASCI, SCAI, SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imagin: a report of the American College of Cardiology Foundation Quality Strategy Directions Committee Appropriateness Criteria Working Group, American College of Radiology , Society of Cardiovascular Computed Tomography, Society of Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions and Society of Interventional Radiology. J Am Coll Cardiol 2006; 48: 1475-1497.
• 43 Schroeder S. et al. Cardiac computed tomography: indications, applications, limitations and training requirements. Eur Heart J 2008; 29: 531-536.
• 44 Inoue K. et al. Serial Coronary CT Angiography-Verified Changes in Plaque Characteristics as an End Point. Evaluation of Effect of Statin Intervention. JACC Cardiovasc Imaging 2010; 3: 691-698.
• 45 Ehara S. et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation 2004; 110: 3424-3429.
• 46 Pundziute G. et al. Head-to-head comparison of coronary plaque evaluation between multislice and intravascular ultrasound radiofrequency data analisis. JACC Cardiovasc Imaging 2008; 1: 176-182.
• 47 Camici PG. et al. Non-invasive anatomic and functional imaging of vascular inflammation and unstable plaque. Eur Heart J 2012; 33: 1309-1317.
• 48 Leber AW. et al. Composition of coronary atherosclerotic plaques in patients with acute myocardial infarction and stable angina pectoris determined by contrast enhanced multislice computed tomography. Am J Cardiol 2003; 91: 714-718.
• 49 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 2006; 47: 1655-1662.
• 50 Motoyama S. et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol 2007; 50: 319-326.
• 51 Motoyama S. et al. Computed tomography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndromes. J Am Coll Cardiol 2009; 54: 49-57.
• 52 Kashiwagi M. et al. Feasibility on noninvasive assessment of thin-cap fibroatheroma by multidetector computed tomography. JACC Cardiovasc Imaging 2009; 2: 1412-1419.
• 53 Maurovich-Horvat P. et al. The napkin-ring sign: CT signature of high-risk coronary plaques?. JACC Cardiovasc Imaging 2010; 3: 440-444.
• 54 Pflederer T. et al. Characterisation of culprit lesions in acute coronary syndromes using coronary dual-source CT angiography. Atherosclerosis 2010; 211: 437-444.
• 55 Hyafil F. et al. Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography. Nat Med 2007; 13: 636-641.
• 56 Hyafil F. et al. Quantification of inflammation with rabbit atherosclerotic plaques using the macrophage-specific CT Contrast agent N1177: a comparison wit 18FDG PET/CT and histology. J Nucl Med 2009; 50: 959-965.
• 57 Weissleder R, Mahmood U. Molecular imaging. Radiology 2001; 219: 316-333.
• 58 Cormode DP. et al. Atheroslerotic plaque composition analysis with multicolour CT and targeted gold nanoparticles. Radiology 2010; 256: 774-782.
• 59 Choudhury RP. et al. Molecular, cellular and functional imaging of atherothrombosis. Nat Rev Drug Discv 2004; 3: 913-925.
• 60 Yuan C. et al. Carotid atherosclerotic plaque: non invasive MR characterisation and identification of vulnerable lesions. Radiology 2001; 221: 285-299.
• 61 Yuan C. et al. In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques. Circulation 2001; 104: 2051-2056.
• 62 Saam T. et al. The vulnerable or high-risk, atherosclerotic plaque: non-invasive MR imaging for characterisation and assessment. Radiology 2007; 244: 64-77.
• 63 Demarco JK. et al. MR carotid plaque imaging and contrast-enhanced MR angiography identifies lesions associated with recent ipsilateral throembolic symptoms: an in vivo study at 3T. Am J Neuroradiol 2010; 31: 1395-1402.
• 64 Takaya N. et al. Association between carotid plaque characteristics and subsequent ischaemic cerebrovascular: a prospective assessment with MRI-initial results. Stroke 2006; 37: 818-823.
• 65 Sadat U. et al. High resolution magnetic resonance imaging-based biochemical stress analysis of carotid atheroma: a comparison of single transient ischaemic attack, recurrent transient ischaemic attacks, non-disabling stroke and asymptomatic patients group . Eur J Vasc Endovasc Surg 2011; 41: 83-90.
• 66 Murphy RE. et al. Characterisation of complicated carotid plaque with magnetic resonance direct thrombus imaging in patients with cerebral ischaemia. Circulation 2003; 107: 3047-3052.
• 67 Zhao X. et al. Discriminating carotid atherosclerotic lesion severity by luminal stenosis and plaque burden. Stroke 2011; 42: 347-353.
• 68 Saam T. et al. Comparison of symptomatic and asymptomatic atherosclerotic carotid plaque features with in vivo MR imaging. Radiology 2006; 240: 464-472.
• 69 Singh N. et al. Moderate carotid artery stenosis: MR imaging-depicted intraplaque hemorrhage predicts risk of cerebrovascular ischaemic events in asymptomatic men. Radiology 2009; 252: 502-508.
• 70 Kolodgie FD. et al. Elimination of neoangiogenesis for plaque stabilisation: is there a role for local drug therapy?. J Am Coll Cardiol 2007; 49: 2093-2101.
• 71 Cappendijk VC. et al. In vivo detection of hemorrhage in human atherosclerotic plaques with magnetic resonance imaging. J Magn Reson I 2004; 20: 105-110.
• 72 Cappendijk VC. et al. Assessment of human atherosclerotic carotid plaque components with mulsequence MR imaging initial experience. Radiology 2005; 234: 487-492.
• 73 Sullivan JL. Iron and sex difference in heart disease risk. Lancet 1981; 1: 1293-1294.
• 74 Raman SV. et al. In vivo atherosclerotic plaque characterisation using magnetic susceptibility distinguished symptom producing plaques. JACC Cardiovasc Imaging 2008; 1: 49-57.
• 75 Camici PG. et al. Non invasive anatomic and functional imaging of vascular inflammation and unstable plaque. Eur Heart J 2012; 33: 1309-1317.
• 76 Wasserman BA. et al. Carotid artery atherosclerosis in vivo morphologic characterisation with gadolinium/enhanced double oblique MR imaging /initial results. Radiology 2002; 223: 566-573.
• 77 Yuan C. et al. Contrast enhanced high resolution MRI for atherosclerotic carotid artery tissue characterisation. J Magn Reson Imaging 2002; 15: 62-67.
• 78 Choudhury RP. et al. Molecular, cellular and functional imaging of atherotrombosis. Nat Rev Drug Discover 2004; 3: 913-925.
• 79 Kerwin WS. et al. Inflammation in carotid atherosclerotic plaque : a dynamic contrast -enhanced MR imaging study. Radiology 2006; 241: 459-468.
• 80 Trivedi RA. et al. Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages . Arterioscler Thromb Vasc Biol 2006; 26: 1601-1606.
• 81 Chu B. et al. Magnetic resonance imaging features of the disruption-prone and the disrupted carotid plaque. JACC Cardiovasc Imaging 2009; 2: 883-896.
• 82 Corti R. et al. Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a longitudinal study by high resolution, non invasive magnetic resonance imaging. Circulation 2001; 104: 249-252.
• 83 Corti R. et al. 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: 106-112.
• 84 Zhao XQ. et al. Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: a case control study. Arterioscler Thromb Vasc Biol 2001; 21: 1623-1629.
• 85 Underhill HR. et al. Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercoesterolemic patients A high-resolution magnetic resonance imaging trial. Am Heart J 2008; 155: 584e1-e8.
• 86 Tang TY. et al. Temporal dependence of in vivo USPIO-enhancement MRI signal changes in human atheromatous carotid plaques. Neuroradiol 2009; 51: 457-465.
• 87 Yun M. et al. F-18FDG uptake in the large arteries: a new observation. Clin Nucl Med 2001; 26: 314-319.
• 88 Rudd JH. et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation 2002; 105: 2708-2711.
• 89 Tawakol A. et al. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Nucl Cardiol 2005; 12: 294-301.
• 90 Rudd JH. et al. (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol 2007; 50: 892-896.
• 91 Mauriello A. et al. Diffuse and active inflammation occurs in both vulnerable and stable plaques of the entire coronary tree: a hystophatologic study of patients dying of acute myocardial infarction. J Am Coll Cardiol 2005; 45: 1585-1593.
• 92 Tahara N. et al. Simvastatin attenuates plaque inflammation. Evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 2006; 48: 1825-1831.
• 93 Wykrzykowska J. et al. Imaging of inflamed and vulnerable plaque in coronary arteries with 18-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J Nucl Med 2009; 50: 563-568.
• 94 Rogers IS. et al. Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. J Am Coll Cardiol Img 2010; 3: 388-397.
• 95 Rominger A. et al. 18FDG-PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 2009; 50: 1611-1620.
• 96 Camici PG. et al. Non-invasive anatomic and functional imaging of vascular inflammation and unstable plaque. Eur Heart J 2012; 33: 1309-1317.
• 97 Matter CM. et al. 18F-choline images murine atherosclerotic plaques ex viv. Artherioscler Thromb Vasc Biol 2006; 260: 584-589.
• 98 Bucerius J. et al. Feasibility of 18F-fluoromethylcholine PET/CT for imaging of vessel wall alterations in humans—first results. Eur J Nucl Med Mol Imaging 2008; 35: 815-820.
• 99 Dweck MR. et al. Coronary arterial 18F-Sodium Fluoride Uptake. A novel marker of plaque biology. J Ann Coll Cardiol 2012; 59: 1539-1548.
• 100 Soloperto G, Casciaro S. Progress in atherosclerotic plaque imaging. World J Radiol 2012; 4: 353-371.
• 101 Johnson LL. et al. 99mTc-annexin V imaging for in vivo detection of atherosclerotic lesions in porcine coronary arteries. J Nucl Med 2005; 46: 1186-1193.
• 102 Isobe S. et al. Noninvasive imaging in atherosclerotic lesions in apolipoprotein E-deficient and low-density-lipoprotein receptor-deficient mice with annexin A5. J Nucl Med 2006; 47: 1497-1505.
• 103 Ishino S. et al. 99mTc-Annexin A5 for noninvasive characterisation of atherosclerotic lesions: imaging and histological studies in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits. Eur J Nucl Med Mol Imaging 2007; 34: 889-899.
• 104 Kietselaer BL. et al. The role of labeled Annexin A5 in imaging of programmed cell death. From animal to clinical imaging. Q J Nucl Med 2003; 47: 349-361.
• 105 Hartung D. et al. Resolution of apoptosis in atherosclerotic plaque by dietary modification and statin therapy. J Nucl Med 2005; 46: 2051-2056.
• 106 Elkhaward M, Rudd JHF. Radiotracer imaging of atherosclerotic plaque biology. Cardiol Clin 2009; 27: 345-354.
• 107 Sakalihasan N, Michel JB. Functional Imaging of Atherosclerosis to Advance Vascular Biology. Eur J Vasc Endovasc Surg 2009; 37: 728-734.
• 108 Ogawa M. et al. Application of 18F-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilisation of vulnerable atherosclerotic plaques. J Nucl Med 2006; 47: 1845-1850.
• 109 Iuliano L. et al. Preparation and biodistribution of 99m-technetium labelled oxidized LDL in man. Atherosclerosis 1996; 126: 131-141.
• 110 Ishino S. et al. Targeting of Lectinlike Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) with 99mTc-Labeled Anti-LOX-1 Antibody: Potential Agent for Imaging of Vulnerable Plaque. J Nucl Med 2008; 49: 1677-1685.
• 111 Li D. et al. Molecular Imaging of Atherosclerotic Plaques Targeted to Oxidized LDL Receptor LOX-1 by SPECT/CT and Magnetic Resonance. Circ Cardiovasc Imaging 2010; 3: 464-472.
• 112 Hardoff R. et al. External imaging of atherosclerosis in rabbits using an 123I-labeled syntetic peptide fragment. J Clin Pharmacol 1993; 33: 1039-1047.
• 113 Demacker PN. et al. Evaluation of indium-111-polyclonal immunoglobulin G to quantitate atherosclerosis in Watanabe heritable hyperlipidemic rabbits with scintigraphy: effect of age and treatment with antioxidants or ethinylestradiol. J Nucl Med 1993; 34: 1316-1321.
• 114 Chakrabarti M. et al. Biodistribution and radioimmunopharmacokinetiks of 131I-Ama monoclonal antibody in atherosclerotic rabbits. Nucl Med Biol 1995; 22: 693-697.
• 115 Narula J. et al. Noninvasive localisation of experimental atherosclerotic lesions with mouse/human chimeric Z2D3 F(ab’)2 specific for the proliferating smooth muscle cells of human atheroma. Imaging with conventional and negative charge-modified antibody fragments. Circulation 1995; 92: 474-484.
• 116 Carrio I. et al. Noninvasive localisation of human atherosclerotic lesions with indium 111-labeled monoclonal Z2D3 antibody specific for proliferating smooth muscle cells. J Nucl Cardiol 1998; 5: 551-557.
• 117 Ohtsuki K. et al. Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions: an autoradiographic study. Circulation 2001; 104: 203-208.
• 118 Bidzhekov K. et al. MCP-1 induces a novel transcription factor with proapoptotic activity. Circ Res 2006; 98: 1107-1109.
• 119 Shah PK. et al. Human Monocyte-Derived Macrophages Induce Collagen Breakdown in Fibrous Caps of Atherosclerotic Plaques: Potential Role of Matrix- Degrading Metalloproteinases and Implications for Plaque Rupture. Circulation 1995; 92: 1565-1569.
• 120 Chenga C. et al. Activation of MMP8 and MMP13 by angiotensin II correlates to severe intra-plaque hemorrhages and collagen breakdown in atherosclerotic lesions with a vulnerable phenotype. Atherosclerosis 2009; 204: 26-33.
• 121 Xie S. et al. Inhibiting extracellular matrix metalloproteinase inducer maybe beneficial for diminishing the atherosclerotic plaque instability. J Postgrad Med 2009; 55: 284-286.
• 122 Fujimoto S. et al. Molecular imaging of matrix metallo- proteinase in atherosclerotic lesions: resolution with dietary modification and statin therapy. J Am Coll Cardiol 2008; 52: 1847-1857.
• 123 Haider N. et al. Dual molecular imaging for targeting metalloproteinase activity and apoptosis in atherosclerosis: molecular imaging facilitates understanding of pathogenesis. J Nucl Cardiol 2009; 16: 753-762.
• 124 Ohshima S. et al. Molecular imaging of matrix metallopro- teinase expression in atherosclerotic plaques of mice deficient in apolipoprotein e or low-density-lipoprotein receptor. J Nucl Med 2009; 50: 612-617.
• 125 Kuge Y. et al. Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterising atherosclerotic plaques. Eur J Nucl Med Mol Imaging 2010; 37: 2093-2104.
• 126 Razavian M. et al. Atherosclerosis Plaque Heterogeneity and Response to Therapy Detected by In Vivo Molecular Imaging of Matrix Metallo- proteinase Activation. J Nucl Med 2011; 52: 1795-1802.
• 127 Lenglet S. et al. Molecular imaging of matrix metalloproteinases in atherosclerotic plaques. Thromb Haemost 2012; 107: 409-416.
• 128 Wagner S. et al. The MMP inhibitor (R)-2-(N-benzyl-4-(2-[18F]fluoroethoxy)phenylsulphonamido)-N-hydroxy-3-methylbutanamide: Improved precursor synthesis and fully automated radiosynthesis. Appl Radiat Isot 2011; 69: 862-868.
• 129 Beller GA. Imaging of vulnerable plaques: will it affect patient management and influence outcomes?. J Nucl Cardiol 2011; 18: 531-533.
• 130 Bom N, Lancee CT. 1972 Apparatus for ultrasonically examining a hollow organ. UK Patent no. 1402192
• 131 Bom N. et al. The technical potential of IVUS: history and principles. In: Vascular ultrasound. Springer; 2003. Tokyo, Japan: pp. 51-65.
• 132 de Korte CL. et al. Vascular ultrasound for atherosclerosis imaging. Interface Focus 2011; 1: 565-575.
• 133 Nissen SE, Yock P. Intravascular ultrasound: novel pathophysiological insights and current clinical applications. Circulation 2001; 103: 604-616.
• 134 Rodriguez-Granillo GA. et al. In vivo variability in quantitative coronary ultrasound and tissue characterisation measurements with mechanical and phased-array catheters. Int J Cardiovasc Imaging 2006; 22: 47-53.
• 135 Goar FG. et al. Intravascular ultrasound imaging of angiographically normal coronary arteries: an in vivo comparison with quantitative angiography. J Am Coll Cardiol 1991; 18: 952-958.
• 136 Gussenhoven EJ. et al. Arterial wall characteristics determined by intravascualar ultrasound imaging: an in vitro study. J Am Coll Cardiol 1989; 14: 947-952.
• 137 Potkin BN. et al. Coronary artery imaging with intravascular high-frequency ultrasound. Circulation 1990; 81: 1575-1585.
• 138 Nishimura RA. et al. Intravascular ultrasound imaging: in vitro validation and patologic correlation. J Am Coll Cardiol 1990; 16: 145-154.
• 139 Nissen SE, Yock P. Intravascular Ultrasound: Novel Pathophysiological Insights and Current Clinical Applications. Circulation 2001; 103: 604-616.
• 140 Mintz GS. et al. American College of Cardiology clinical expert consensus document on standards for acquisition measurements 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 2001; 37: 1478-1492.
• 141 Layland J. et al. Virtual Histology: A Window to the Heart of Atherosclerosis. Heart Lung Circ 2011; 20: 615-621.
• 142 Kume T. et al. Assessment of coronary arterial thrombus by optical coherence tomography. Am J Cardiol 2006; 97: 1713-1717.
• 143 Low AF. et al. In vivo characterisation of coronary plaques with conventional grey-scale intravascular ultrasound: correlation with optical coherence tomography. EuroIntervention 2009; 4: 626-632.
• 144 Yamagishi M. et al. Morphology of Vulnerable Coronary Plaque: Insights from Follow-up of patients Examined by Intravascula Ultrasound Before an Acute Coronary Syndrome. J Am Coll Cardiol Vol 2000; 35: 106-111.
• 145 Nair A. et al. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation 2002; 106: 2200-2206.
• 146 Virmani R. et al. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006; 47: C13-C18.
• 147 Ishikawa Y. et al. Histopathologic profiles of coronary atherosclerosis by myocardial bridge underlying myocardial infarction. Atherosclerosis 2013; 226: 118-123.
• 148 Montecucco F. et al. Systemic and intraplaque mediators of inflammation are increased in patients symptomatic for ischaemic stroke. Stroke 2010; 41: 1394-1404.
• 149 Davies MJ. et al. Risk of thrombosis in human atherosclerotic plaques: role of extracellularlipid, macrophage, and smooth muscle cell content. Br Heart J 1993; 69: 377-381.
• 150 Felton CV. et al. Relation of plaque lipid composition and morphology to the stability of human aortic plaques. Arterioscler Thromb Vasc Biol 1997; 17: 1337-1345.
• 151 Virmani R. et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerosis lesions. Arterioscler Thromb Vasc Biol 2000; 20: 1262-1275.
• 152 Rodriguez-Granillo GA. et al. In vivo intravascular ultrasound-derived thin-cap fibroatheroma detection using ultrasound radiofrequency data analysis. J Am Coll Cardiol 2005; 46: 2038-2042.
• 153 Burke AP. et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997; 336: 1276-1282.
• 154 Nair ACD, Vince DG. Regularized autoregressive analysis of intravascular ultrasound data: improvement in spatial accuracy of plaque tissue maps. IEEE Trans Ultrason Ferroelectr Freq Control 2004; 51: 420-431.
• 155 Tian J. et al. Effect of statin therapy on the progression of coronary atherosclerosis. BMC Cardiovasc Disord 2012; 1 (12) 70
• 156 de Korte CL. et al. Characterisation of plaque components with intravascular ultrasound elastography in human femoral and coronary arteries in vitro. Circulation 2000; 102: 617-623.
• 157 Richarda MS, Doyley MM. Investigating the impact of spiral priors on the performance of model-based IVUS elastography. Phys Med Biol 2011; 56: 7223-7246.
• 158 Liang Y. et al. Measurement od 3D arterial wall strain tensor using intravascular B-mode ultrasound images: a feasibility study. Phys Med Biol 2010; 55: 6377-6394.
• 159 Burke AP. et al. Coronary calcification: insights from sudden coronary death victims. Z Kardiol 2000; 89: 49-53.
• 160 Rasheed Q. et al. Correlation of intracoronary ultrasound plaque characteristics in atherosclerotic coronary artery disease patients with clinical variables. Am J Cardiol 1994; 73: 753-758.
• 161 Nakamura M. et al. Impact of coronary artery remodelling on clinical presentation of coronary artery disease: an intravascular ultrasound study. J Am Coll Cardiol 2001; 37: 63-69.
• 162 Fujii K. et al. Intravascular Ultrasound Study of Patterns of Calcium in Ruptured Coronary Plaques. Am J Cardiol 2005; 96: 352-357.
• 163 Lee JB. et al. Histopathologic Validation of the Intravascular Ultrasound Diagnosis of Calcified Coronary Artery Nodules. Am J Cardiol 2011; 108: 1547-1551.
• 164 Virmani R. et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000; 20: 1262-1275.
• 165 Nishioka T. et al. Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: an in vivo intravascular ultrasound study. J Am Coll Cardiol 1996; 27: 1571-1576.
• 166 Mintz GS. et al. Contribution of inadequate arterial remodelling to the development of focal coronary artery stenosis: an intravascular ultrasound study. Circulation 1997; 95: 1791-1798.
• 167 Birnbaum Y. et al. Regional remodelling of atherosclerotic srteries: a major determinant of clinical manifestations of disease. J Am Coll Cardiol 1997; 30: 1149-1164.
• 168 Mintz GS. et al. Arterial remodelling after coronary angioplasty: a serial intravascular ultrasound study. Circulation 1996; 94: 35-43.
• 169 Kimura T. et al. Remodelling of human coronary arteries undergoing coronary angioplasty or atherectomy. Circulation 1997; 96: 475-483.
• 170 Hartmann M. et al. Relation between baseline plaque burden and subsequent remodelling of atherosclerotic left main coronary arteries: a serial intravascular ultrasound study with long-term (> or = 12 months) follow-up. Eur Heart J 2006; 27: 1778-1784.
• 171 von Birgelen C. et al. Remodelling index compared to actual vascular remodelling in atherosclerotic left main coronary arteries as assessed with long-term (> or = 12 months) serial vascular ultrasound. J Am Coll Cardiol 2006; 47: 1363-1368.
• 172 Hong YJ. et al. Positive remodelling is associated with vulnerable coronary plaque commponents regrdless of clinical presentation: Virtual histology-intravascular ultrasound analysis. Int J Cardiol. 2012. epub ahead of print.
• 173 Moreno PR. Vulnerable Plaque: Definition, Diagnosis, and Treatment. Cardiol Clin 2010; 28: 1-30.
• 174 Barger AC. et al. Vasa vasorum and neovascularisation of human coronary arteries - a possible role in the pathophysiology of atherosclerosis. N Engl J Med 1984; 310: 175-177.
• 175 Depre C. et al. Neovascularisation in human coronary atherosclerotic lesions. Cathet Cardiovasc Design 1996; 39: 215-220.
• 176 Ritman EL, Lerman A. Role of vasa vasorum in arterial disease: a re-emerging factor. Curr Cardiol Rev 2007; 3: 43-55.
• 177 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. Intern J Cardiol 2008; 130: 23-29.
• 178 Carlier S. et al. Vasa vasorum imaging: a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep 2005; 7: 164-169.
• 179 O’Malley SM. et al. Intravascular ultrasound based imaging of vasa vasorum for the detection of vulnerable atherosclerotic plaque. Proc. Int Conf Med Image Comput Assist Intery 2005; 8: 343-351.
• 180 Vavuranakis M. et al. Detection of luminal - intimal border and coronary wall enhancement in intravascular ultrasound imaging after injection of microbubbles and simultaneous sonication with transthoracic echocardiography. Circulation 2005; 112: e1-e2.
• 181 Maresca D. et al. Contrast-enhanced ntravascular ultrasound 3D reconstruction of a vasa vasorum mimicking model. In: Proceedings IEEE Int Ultrasonics Symp. San Diego, CA, USA: 11-14 October 2010
• 182 Kume T. et al. Assessment of coronary intima—media thickness by optical coherence tomography: comparison with intravascular ultrasound. Circ J, 2005; 69: 903-907.
• 183 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 2010; 31: 401-415.
• 184 Kitabata H. et al. Relation of microchannel structure identified by optical coherence tomography to plaque vulnerability in patients with coronary artery disease. Am J Cardiol 2010; 105: 1673-1678.
• 185 Vorpahl M. et al. Small black holes in optical frequency domain imaging matches intravascular neoangiogenesis formation in histology. Eur Heart J 2010; 31: 1889.
• 186 Uemura S. et al. Thin-cap fibroatheroma and microchannel findings in optical coherence tomography correlate with subsequent progression of coronary atheromatous plaques. Eur Heart J 2012; 33: 78-85.
• 187 Virmani R. et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Atherioscler Thromb Vasc Biol 2000; 20: 1262-1275.
• 188 Burke AP. et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Eng J Med 1997; 336: 1276-1282.
• 189 Jang IK. et al. In vivo characterisation of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation 2005; 111: 1551-1555.
• 190 Kume T. et al. Measurement of the thickness of the fibrous cap by optical coherence tomography. Am Heart J 2006; 152: e1-e4.
• 191 Sawada T. et al. Feasibility of combined use of intravascular ultrasound radiofrequency data analysis and optical coherence tomography for detecting thin-cap fibroatheroma. Eur Heart J 2008; 29: 1136-1146.
• 192 Yonetsu T. et al. In vivo critical fibrous cap thickness for rupture-prone coronary plaques assessed by optical coherence tomography. Eur Heart J 2011; 32: 1251-1259.
• 193 Wang Z. et al. Volumetric quantification of fibrous caps using intravascular optical coherence tomography. Biomed Opt Express 2012; 3: 1413-1426.
• 194 Tearney GJ. et al. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation 2003; 107: 113-119.
• 195 MacNeill BD. et al. Focal and multifocal plaque macrophage distributions in patients with acute and stable presentations of coronary artery diseas. J Am Coll Cardiol 2004; 44: 972-979.
• 196 Kato K. et al. Nonculprit plaques in patients with acute coronary syndromes have more vulnerable features compared with those with non-acute coronary syndromes. Cardiovasc Imaging 2012; 5: 433-440.
• 197 Yabushita H. et al. Characterisation of human atherosclerosis by optical coherence tomography. Circulation 2002; 106: 1640-16445.
• 198 Manfrini O. et al. Sources of error and interpretation of plaque morphology by optical coherence tomography. Am J Cardiol 2006; 98: 156-159.
• 199 Mintz GS. et al. Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation 1995; 91: 1959-1965.
• 200 Callister TQ. et al. Coronary artery disease: improved reproducibility of calcium scoring with an electron beam CT volumetric method. Radiology 1998; 208: 807-814.
• 201 Tanigawa J. et al. Heavily calcified coronary lesions preclude stent apposition despite high pressure balloon dilatation and rotational atherectomy: in vivo demonstration with optical coherence tomography. Circ J 2008; 72: 157-160.
• 202 Tanimoto T. et al. Various types of plaque disruption in culprit coronary artery visualized by optical coherence tomography in a patient with unstable angina. Circ J 2009; 73: 187-189.
• 203 Stefano GT. et al. Utilisation of frequency domain optical coherence tomography and fractional flow reserve to assess intermediate coronary artery stenoses: conciliating anatomic and physiologic information. Int J Cardiovasc Imaging 2011; 27: 299-308.
• 204 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 2007; 50: 933-939.
• 205 Chen BX. et al. Characterisation of atherosclerotic plaque in patients with unstable angina pectoris and stable angina pectoris by optical coherence tomography. Zhonghua Xin Xue Guan Bing Za Zhi. 2009; 37: 422-425.
• 206 Mizukoshi M. et al. Clinical classification and plaque morphology determined by optical coherence tomography in unstable angina pectoris. Am J Cardiol 2010; 106: 323-328.
• 207 Jang IK. et al. Visualisation of coronary atherosclerotic plaques in patient using optical coherence tomography: comparison with intravascular ultrasound. J Am Cardiol 2002; 39: 604-609.
• 208 Meng L. et al. In vio optical coherence tomography of experimental thrombosis in a rabbit carotid model. Heart 2008; 94: 777-780.
• 209 Bezerra HG. et al. Intracoronary optical coherence tomography: a comprehensive review clinical and research applications. JACC Cardiovasc Interv 2009; 2: 1035-1046.
• 210 Kume T. et al. Relationship between coronary remodelling and plaque characterisation in patients without clinical evidence of coronary artery disease. Atherosclerosis 2008; 197: 799-805.
• 211 Raffel OC. et al. In vivo association between positive coronary artery remodelling and coronary plaque characteristics assessed by intravascular optical coherence tomography. Eur Heart J 2008; 29: 1721-1728.
• 212 Rathore S. et al. Association of coronary plaque composition and arterial remodelling: A optical coherence tomography study. Atherosclerosis 2012; 221: 405-415.
• 213 Kubo T. et al. Virtual histology intravascular ultrasound compared with optical coherence tomography for identifcation of thin-cap fibroatheroma. Int Heart J 2011; 52: 175-179.
• 214 Kubo T, Akasaka T. OCT-ready for prime time? Clinical applications of optical coherence tomography. Cardiac Interv Today 2009; 4: 35-37.
• 215 Takarada S. et al. Advantage of next generation frequency-domain optical coherence tomography compared with conventional time-domain system in the assessment of coronary lesions. Catheter and Cardiovasc Interv 2010; 75: 202-206.
• 216 Kubo T, Akasaka T. Optical coherence tomography imaging: current status and future perspectives- current and future developments in OCT. Cardiovasc Interv Therap 2009; 25: 2-10.
• 217 Tearney GJ. et al. Optical coherence tomography for imaging in the vulnerable plaque. J Biomed Opt 2006; 11: 021002.
• 218 Tearney GJ. et al. Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging. JACC: Cardiovasc Imag 2008; 1: 752-761.
• 219 Gao D. et al. Computed tomography for detecting coronary artery plaques: a meta-analysis. Atherosclerosis 2011; 219: 603-609.
• 220 Deliargyris EN. Intravascular ultrasound virtual histology derived thin cap fibroatheroma: now you see it, now you don’t. J Am Coll Cardiol 2010; 55: 1598-1599.
• 221 Nahrendorf M. et al. Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 2006; 114: 1504-1511.