Abstract
A major contributor to the occurrence of ischaemic stoke is the existence of carotid atherosclerosis. A vulnerable carotid atherosclerotic plaque may rupture or erode, thus causing a thrombotic effect. Currently, clinical decision making with regard to carotid endarterectomy or stenting is still primarily based on the extent of luminal stenosis, estimated with CT angiography and/or (duplex) ultrasonography. However, there is growing evidence that the anatomic impact of stenosis alone has limited value in predicting the exact consequences of plaque vulnerability. Various molecular processes have, independently of degree of stenosis, shown to be importantly associated with the plaque’s capability to cause thrombotic events. These molecular processes can be visualised with nuclear medicine techniques allowing the identification of vulnerable patients by noninvasive in vivo SPECT(/CT) and PET(/CT) imaging. This chapter provides an overview of SPECT(/CT) and PET(/CT) imaging with specific radiotracers that have been evaluated for the detection of plaques together with a future perspective in this field of imaging.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Annovazzi A, Bonanno E, Arca M, D’Alessandria C, Marcoccia A, Spagnoli LG et al (2006) 99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques. Eur J Nucl Med Mol Imaging 33(2):117–126
Bamford J, Sandercock P, Dennis M, Burn J, Warlow C (1991) Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 337(8756):1521–1526
Barger AC, Beeuwkes R III, Lainey LL, Silverman KJ (1984) Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N Engl J Med 310(3):175–177
Blankenberg FG, Backer MV, Levashova Z, Patel V, Backer JM (2006) In vivo tumor angiogenesis imaging with site-specific labeled (99m)Tc-HYNIC-VEGF. Eur J Nucl Med Mol Imaging 33(7):841–848
Boyle JJ, Wilson B, Bicknell R, Harrower S, Weissberg PL, Fan TP (2000) Expression of angiogenic factor thymidine phosphorylase and angiogenesis in human atherosclerosis. J Pathol 192(2):234–242
Bucerius J, Schmaljohann J, Bohm I, Palmedo H, Guhlke S, Tiemann K et al (2008) Feasibility of 18F-fluoromethylcholine PET/CT for imaging of vessel wall alterations in humans–first results. Eur J Nucl Med Mol Imaging 35(4):815–820
Bucerius J, Duivenvoorden R, Mani V, Moncrieff C, Rudd JH, Calcagno C et al (2011) Prevalence and risk factors of carotid vessel wall inflammation in coronary artery disease patients: FDG-PET and CT imaging study. JACC Cardiovasc Imaging 4(11):1195–1205
Chen J, Tung CH, Mahmood U, Ntziachristos V, Gyurko R, Fishman MC et al (2002) In vivo imaging of proteolytic activity in atherosclerosis. Circulation 105(23):2766–2771
Collingridge DR, Carroll VA, Glaser M, Aboagye EO, Osman S, Hutchinson OC et al (2002) The development of [(124)I]iodinated-VG76e: a novel tracer for imaging vascular endothelial growth factor in vivo using positron emission tomography. Cancer Res 62(20):5912–5919
Corti R, Fuster V (2011) Imaging of atherosclerosis: magnetic resonance imaging. Eur Heart J 32(14):1709–1719
Dangas G, Mehran R, Harpel PC, Sharma SK, Marcovina SM, Dube G et al (1998) Lipoprotein(a) and inflammation in human coronary atheroma: association with the severity of clinical presentation. J Am Coll Cardiol 32(7):2035–2042
Davies JR, Rudd JH, Fryer TD, Graves MJ, Clark JC, Kirkpatrick PJ et al (2005) Identification of culprit lesions after transient ischemic attack by combined 18F fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging. Stroke 36(12):2642–2647
Deguchi JO, Aikawa M, Tung CH, Aikawa E, Kim DE, Ntziachristos V et al (2006) Inflammation in atherosclerosis: visualizing matrix metalloproteinase action in macrophages in vivo. Circulation 114(1):55–62
Derlin T, Richter U, Bannas P, Begemann P, Buchert R, Mester J et al (2010) Feasibility of 18F-sodium fluoride PET/CT for imaging of atherosclerotic plaque. J Nucl Med 51(6):862–865
Derlin T, Wisotzki C, Richter U, Apostolova I, Bannas P, Weber C et al (2011a) In vivo imaging of mineral deposition in carotid plaque using 18F-sodium fluoride PET/CT: correlation with atherogenic risk factors. J Nucl Med 52(3):362–368
Derlin T, Toth Z, Papp L, Wisotzki C, Apostolova I, Habermann CR et al (2011b) Correlation of inflammation assessed by 18F-FDG PET, active mineral deposition assessed by 18F-fluoride PET, and vascular calcification in atherosclerotic plaque: a dual-tracer PET/CT study. J Nucl Med 52(7):1020–1027
Di Gialleonardo V, Signore A, Glaudemans AW, Dierckx RA, De Vries EF (2012) N-(4-18F-fluorobenzoyl)interleukin-2 for PET of human-activated T lymphocytes. J Nucl Med 53(5):679–686
Dweck MR, Chow MW, Joshi NV, Williams MC, Jones C, Fletcher AM et al (2012) Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol 59(17):1539–1548
Elkind MS, Rundek T, Sciacca RR, Ramas R, Chen HJ, Boden-Albala B et al (2005) Interleukin-2 levels are associated with carotid artery intima-media thickness. Atherosclerosis 180(1):181–187
Falk E (2006) Pathogenesis of atherosclerosis. J Am Coll Cardiol 47(8 Suppl):C7–C12
Faust A, Wagner S, Law MP, Hermann S, Schnockel U, Keul P et al (2007) The nonpeptidyl caspase binding radioligand (S)-1-(4-(2-[18F]Fluoroethoxy)-benzyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin ([18F]CbR) as potential positron emission tomography-compatible apoptosis imaging agent. Q J Nucl Med Mol Imaging 51(1):67–73
Ferrara N, vis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18(1):4–25
Forster S, Rominger A, Saam T, Wolpers S, Nikolaou K, Cumming P et al (2010) 18F-fluoroethylcholine uptake in arterial vessel walls and cardiovascular risk factors: correlation in a PET-CT study. Nuklearmedizin 49(4):148–153
Frias JC, Williams KJ, Fisher EA, Fayad ZA (2004) Recombinant HDL-like nanoparticles: a specific contrast agent for MRI of atherosclerotic plaques. J Am Chem Soc 126(50):16316–16317
Fujimoto S, Hartung D, Ohshima S, Edwards DS, Zhou J, Yalamanchili P et al (2008) Molecular imaging of matrix metalloproteinase in atherosclerotic lesions: resolution with dietary modification and statin therapy. J Am Coll Cardiol 52(23):1847–1857
Gerber HP, Ferrara N (2005) Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res 65(3):671–680
Glaudemans AW, Slart RH, Bozzao A, Bonanno E, Arca M, Dierckx RA et al (2010) Molecular imaging in atherosclerosis. Eur J Nucl Med Mol Imaging 37(12):2381–2397
Golestani R, Zeebregts CJ, Terwisscha van Scheltinga AG, Lub-de Hooge MN, van Dam GM, Glaudemans AW, et al (2012) Feasibility of VEGF imaging in human atherosclerotic plaque using 89Zr-bevacizumab positron emission tomography. Mol Imaging 12(4):235–243
Haider N, Hartung D, Fujimoto S, Petrov A, Kolodgie FD, Virmani R et al (2009) Dual molecular imaging for targeting metalloproteinase activity and apoptosis in atherosclerosis: molecular imaging facilitates understanding of pathogenesis. J Nucl Cardiol 16(5):753–762
Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J et al (2004) Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 363(9420):1491–1502
Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695
Hermus L, Lefrandt JD, Tio RA, Breek JC, Zeebregts CJ (2010) Carotid plaque formation and serum biomarkers. Atherosclerosis 213(1):21–29
Holm PW, Slart RH, Zeebregts CJ, Hillebrands JL, Tio RA (2009) Atherosclerotic plaque development and instability: a dual role for VEGF. Ann Med 41(4):257–264
Huang B, Law MW, Khong PL (2009) Whole-body PET/CT scanning: estimation of radiation dose and cancer risk. Radiology 251(1):166–174
Iuliano L, Signore A, Vallabajosula S, Colavita AR, Camastra C, Ronga G et al (1996) Preparation and biodistribution of 99m technetium labelled oxidized LDL in man. Atherosclerosis 126(1):131–141
Izquierdo-Garcia D, Davies JR, Graves MJ, Rudd JH, Gillard JH, Weissberg PL et al (2009) Comparison of methods for magnetic resonance-guided [18-F]fluorodeoxyglucose positron emission tomography in human carotid arteries: reproducibility, partial volume correction, and correlation between methods. Stroke 40(1):86–93
Jones CB, Sane DC, Herrington DM (2003) Matrix metalloproteinases: a review of their structure and role in acute coronary syndrome. Cardiovasc Res 59(4):812–823
Kato K, Schober O, Ikeda M, Schafers M, Ishigaki T, Kies P et al (2009) Evaluation and comparison of 11C-choline uptake and calcification in aortic and common carotid arterial walls with combined PET/CT. Eur J Nucl Med Mol Imaging 36(10):1622–1628
Kietselaer BL, Reutelingsperger CP, Heidendal GA, Daemen MJ, Mess WH, Hofstra L et al (2004) Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis. N Engl J Med 350(14):1472–1473
Kolodgie FD, Petrov A, Virmani R, Narula N, Verjans JW, Weber DK et al (2003) Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque. Circulation 108(25):3134–3139
Kurihara H, Honda N, Kono Y, Arai Y (2012) Radiolabelled agents for PET imaging of tumor hypoxia. Curr Med Chem 19(20):3282–3289
Laitinen I, Saraste A, Weidl E, Poethko T, Weber AW, Nekolla SG et al (2009) Evaluation of alphavbeta3 integrin-targeted positron emission tomography tracer 18F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice. Circ Cardiovasc Imaging 2(4):331–338
Lees AM, Lees RS, Schoen FJ, Isaacsohn JL, Fischman AJ, Mckusick KA et al (1988) Imaging human atherosclerosis with 99mTc-labeled low density lipoproteins. Arteriosclerosis 8(5):461–470
Libby P, Theroux P (2005) Pathophysiology of coronary artery disease. Circulation 111(25):3481–3488
Littlewood TD, Bennett MR (2003) Apoptotic cell death in atherosclerosis. Curr Opin Lipidol 14(5):469–475
Loftus IM, Naylor AR, Goodall S, Crowther M, Jones L, Bell PR et al (2000) Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption. Stroke 31(1):40–47
Lu E, Wagner WR, Schellenberger U, Abraham JA, Klibanov AL, Woulfe SR et al (2003) Targeted in vivo labeling of receptors for vascular endothelial growth factor: approach to identification of ischemic tissue. Circulation 108(1):97–103
Marnane M, Merwick A, Sheehan OC, Hannon N, Foran P, Grant T et al (2012) Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence. Ann Neurol 71(5):709–718
Masteling MG, Zeebregts CJ, Tio RA, Breek JC, Tietge UJ, de Boer JF et al (2011) High-resolution imaging of human atherosclerotic carotid plaques with micro 18 F-FDG PET scanning exploring plaque vulnerability. J Nucl Cardiol 18(6):1066–1075
Mauriello A, Servadei F, Sangiorgi G, Anemona L, Giacobbi E, Liotti D et al (2011) Asymptomatic carotid plaque rupture with unexpected thrombosis over a non-canonical vulnerable lesion. Atherosclerosis 218(2):356–362
Morgan AR, Rerkasem K, Gallagher PJ, Zhang B, Morris GE, Calder PC et al (2004) Differences in matrix metalloproteinase-1 and matrix metalloproteinase-12 transcript levels among carotid atherosclerotic plaques with different histopathological characteristics. Stroke 35(6):1310–1315
Nagengast WB, de Vries EG, Hospers GA, Mulder NH, de Jong JR, Hollema H et al (2007) In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J Nucl Med 48(8):1313–1319
Naghavi M, Falk E, Hecht HS, Jamieson MJ, Kaul S, Berman D et al (2006) From vulnerable plaque to vulnerable patient–Part III: executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report. Am J Cardiol 98(2A):2H–15H
Nahrendorf M, Jaffer FA, Kelly KA, Sosnovik DE, Aikawa E, Libby P et al (2006) Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 114(14):1504–1511
Nighoghossian N et al (2005) The vulnerable carotid artery plaque: current imaging methods and new perspectives. Stroke 36(12):2764–2772
Patlak CS, Blasberg RG, Fenstermacher JD (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3(1):1–7
Pichler BJ, Kolb A, Nagele T, Schlemmer HP (2010) PET/MRI: paving the way for the next generation of clinical multimodality imaging applications. J Nucl Med 51(3):333–336
Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S et al (2009) 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 50(10):1611–1620
Rossin R, Muro S, Welch MJ, Muzykantov VR, Schuster DP (2008) In vivo imaging of 64Cu-labeled polymer nanoparticles targeted to the lung endothelium. J Nucl Med 49(1):103–111
Rousset OG, Ma Y, Evans AC (1998) Correction for partial volume effects in PET: principle and validation. J Nucl Med 39(5):904–911
Rudd JHF, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N et al (2002) Imaging atherosclerotic plaque inflammation with [F-18]-fluorodeoxyglucose positron emission tomography. Circulation 105(23):2708–2711
Sanidas EA, Mintz GS, Maehara A, Cristea E, Wennerblom B, Iniguez A et al (2012) Adverse cardiovascular events arising from atherosclerotic lesions with and without angiographic disease progression. JACC Cardiovasc Imaging 5(3 Suppl):S95–S105
Sayed S, Cockerill GW, Torsney E, Poston R, Thompson MM, Loftus IM (2009) Elevated tissue expression of thrombomodulatory factors correlates with acute symptomatic carotid plaque phenotype. Eur J Vasc Endovasc Surg 38(1):20–25
Schafers M, Riemann B, Kopka K, Breyholz HJ, Wagner S, Schafers KP et al (2004) Scintigraphic imaging of matrix metalloproteinase activity in the arterial wall in vivo. Circulation 109(21):2554–2559
Signore A, Capriotti G, Scopinaro F, Bonanno E, Modesti A (2003) Radiolabelled lymphokines and growth factors for in vivo imaging of inflammation, infection and cancer. Trends Immunol 24(7):395–402
Skajaa T, Cormode DP, Falk E, Mulder WJ, Fisher EA, Fayad ZA (2010) High-density lipoprotein-based contrast agents for multimodal imaging of atherosclerosis. Arterioscler Thromb Vasc Biol 30(2):169–176
Skalen K, Gustafsson M, Rydberg EK, Hulten LM, Wiklund O, Innerarity TL et al (2002) Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature 417(6890):750–754
Slart RH, Zeebregts CJ, Tio RA (2008) Can nuclear medicine shed light on the dark side of angiogenesis in cardiovascular disease? Nucl Med Commun 29(7):585–587
Sluimer JC, Daemen MJ (2009) Novel concepts in atherogenesis: angiogenesis and hypoxia in atherosclerosis. J Pathol 218(1):7–29
Sluimer JC, Kolodgie FD, Bijnens AP, Maxfield K, Pacheco E, Kutys B et al (2009) Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage. J Am Coll Cardiol 53(17):1517–1527
Spagnoli LG, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, Schwartz RS et al (2004) Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA 292(15):1845–1852
Szabo Z, Speth RC, Brown PR, Kerenyi L, Kao PF, Mathews WB et al (2001) Use of positron emission tomography to study AT1 receptor regulation in vivo. J Am Soc Nephrol 12(7):1350–1358
Takaya N, Yuan C, Chu B, Saam T, Polissar NL, Jarvik GP et al (2005) Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study. Circulation 111(21):2768–2775
Van de Wiele C, Oltenfreiter R (2006) Imaging probes targeting matrix metalloproteinases. Cancer Biother Radiopharm 21(5):409–417
van der Vaart MG, Meerwaldt R, Reijnen MM, Tio RA, Zeebregts CJ (2008) Endarterectomy or carotid artery stenting: the quest continues. Am J Surg 195(2):259–269
Virmani R, Kolodgie FD, Burke AP, Finn AV, Gold HK, Tulenko TN et al (2005) Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol 25(10):2054–2061
Wallis de Vries B, Hillebrands JL, van Dam GM, Tio RA, de Jong JS et al (2009) Images in cardiovascular medicine. Multispectral near-infrared fluorescence molecular imaging of matrix metalloproteinases in a human carotid plaque using a matrix-degrading metalloproteinase-sensitive activatable fluorescent probe. Circulation 119(20):e534–e536
Yun M, Jang S, Cucchiara A, Newberg AB, Alavi A (2002) 18 F FDG uptake in the large arteries: a correlation study with the atherogenic risk factors. Semin Nucl Med 32(1):70–76
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Slart, R.H.J.A., Boersma, H.H., Zeebregts, C.J. (2014). Carotid Plaque Imaging with SPECT/CT and PET/CT. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Leenders, K. (eds) PET and SPECT in Neurology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54307-4_22
Download citation
DOI: https://doi.org/10.1007/978-3-642-54307-4_22
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-54306-7
Online ISBN: 978-3-642-54307-4
eBook Packages: MedicineMedicine (R0)