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Emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries

  • Wengen Chen
  • Gonca G. Bural
  • Drew A. Torigian
  • Daniel J. Rader
  • Abass AlaviEmail author
Review Article

Abstract

Atherosclerosis is a dynamic inflammatory disorder. The biological composition and inflammatory state of an atherosclerotic plaque, rather than the degree of stenosis or its size are the major determinants of acute clinical events. A noninvasive technique to detect vulnerable atherosclerotic plaque is critically needed. FDG-PET/CT, a combined functional and structural whole-body imaging modality, holds great potential for this purpose. FDG uptake in large arteries has been frequently observed and is associated with cardiovascular risk factors. FDG accumulates in plaque macrophages and uptake is correlated with macrophage density. It is known that vascular FDG uptake and calcification do not overlap significantly and changes of FDG uptake are common, suggesting that FDG uptake may represent a dynamic inflammatory process. It has been reported that vascular FDG uptake can be attenuated by simvastatin in patients, and by the antiinflammatory drug probucol in rabbits. Vascular FDG uptake has been linked to cardiovascular events in some preliminary studies. Data from basic sciences, and animal and clinical studies support the emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries in humans.

Keywords

FDG-PET/CT Atherosclerosis 

Notes

Acknowledgments

The study was supported by a pilot grant from the Society of Nuclear Medicine, and a T32 training grant from NIH (1-T32 CA093258A85-01A1) to W. Chen.

Conflict of Interest

There are no conflicts of interest for the authors.

References

  1. 1.
    Glass CK, Witztum JL. Atherosclerosis, the road ahead. Cell 2001;104:503–16.PubMedCrossRefGoogle Scholar
  2. 2.
    Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, et al. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 2003;5:781–92.PubMedCrossRefGoogle Scholar
  3. 3.
    Li Y, Schwabe RF, DeVries-Seimon T, Yao PM, Gerbod-Giannone MC, Tall AR, et al. Free cholesterol-loaded macrophages are an abundant source of tumor necrosis factor-alpha and interleukin-6: model of NF-kappaB- and map kinase-dependent inflammation in advanced atherosclerosis. J Biol Chem 2005;280:21763–72.PubMedCrossRefGoogle Scholar
  4. 4.
    Semenkovich CF. Insulin resistance and atherosclerosis. J Clin Invest 2006;116:1813–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Repa JJ, Mangelsdorf DJ. The liver X receptor gene team: potential new players in atherosclerosis. Nat Med 2002;8:1243–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the unstable plaque. Prog Cardiovasc Dis 2002;44:349–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Robbie L, Libby P. Inflammation and atherothrombosis. Ann N Y Acad Sci 2001;947:167–79; discussion 179–80.PubMedGoogle Scholar
  8. 8.
    Libby P. Inflammation in atherosclerosis. Nature 2002;420:868–74.PubMedCrossRefGoogle Scholar
  9. 9.
    van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994;89:36–44.PubMedGoogle Scholar
  10. 10.
    Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 1988;12:56–62.PubMedCrossRefGoogle Scholar
  11. 11.
    Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 1988;78:1157–66.PubMedGoogle Scholar
  12. 12.
    Myerburg RJ. Sudden cardiac death in persons with normal (or near normal) hearts. Am J Cardiol 1997;79:3–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 1992;326:310–18.PubMedGoogle Scholar
  14. 14.
    Pasterkamp G, Schoneveld AH, van der Wal AC, Haudenschild CC, Clarijs RJ, Becker AE, et al. Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. J Am Coll Cardiol 1998;32:655–62.PubMedCrossRefGoogle Scholar
  15. 15.
    Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation 1995;92:2157–62.PubMedGoogle Scholar
  16. 16.
    Toussaint JF, LaMuraglia GM, Southern JF, Fuster V, Kantor HL. Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo. Circulation 1996;94:932–8.PubMedGoogle Scholar
  17. 17.
    Eliasziw M, Rankin RN, Fox AJ, Haynes RB, Barnett HJ. Accuracy and prognostic consequences of ultrasonography in identifying severe carotid artery stenosis. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. Stroke 1995;26:1747–52.PubMedGoogle Scholar
  18. 18.
    Plump AS, Smith JD, Hayek T, Aalto-Setala K, Walsh A, Verstuyft JG, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 1992;71:343–53.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 1992;258:468–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Laitinen I, Marjamaki P, Haaparanta M, Savisto N, Laine VJ, Soini SL, et al. Non-specific binding of [(18)F]FDG to calcifications in atherosclerotic plaques: experimental study of mouse and human arteries. Eur J Nucl Med Mol Imaging 2006;33:1461–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhao Y, Kuge Y, Zhao S, Morita K, Inubushi M, Strauss HW, et al. Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE-/- mice. Eur J Nucl Med Mol Imaging 2007;34:1747–55.PubMedCrossRefGoogle Scholar
  22. 22.
    Tai YC, Ruangma A, Rowland D, Siegel S, Newport DF, Chow PL, et al. Performance evaluation of the microPET focus: a third-generation microPET scanner dedicated to animal imaging. J Nucl Med 2005;46:455–63.PubMedGoogle Scholar
  23. 23.
    Ogawa M, Ishino S, Mukai T, Asano D, Teramoto N, Watabe H, et al. (18)F-FDG accumulation in atherosclerotic plaques: immunohistochemical and PET imaging study. J Nucl Med 2004;45:1245–50.PubMedGoogle Scholar
  24. 24.
    Davies JR, Rudd JH, Fryer TD, Graves MJ, Clark JC, Kirkpatrick PJ, et al. Identification of culprit lesions after transient ischemic attack by combined 18F fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging. Stroke 2005;36:2642–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Rudd JH, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation 2002;105:2708–11.PubMedCrossRefGoogle Scholar
  26. 26.
    Tawakol A, Migrino RQ, Hoffmann U, Abbara S, Houser S, Gewirtz H, et al. Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. J Nucl Cardiol 2005;12:294–301.PubMedCrossRefGoogle Scholar
  27. 27.
    Rudd JH, Fayad ZA, Machac J, Weissberg PL, Davies JR, Warburton EA, et al. Response to ‘Laurberg JM, Olsen AK, Hansen SB, et al. Imaging of vulnerable atherosclerotic plaques with FDG-microPET: no FDG accumulation’ [Atherosclerosis 2006]. Atherosclerosis 2007;192:453–4; author reply 451–2.PubMedCrossRefGoogle Scholar
  28. 28.
    Laurberg JM, Olsen AK, Hansen SB, Bottcher M, Morrison M, Ricketts SA, et al. Imaging of vulnerable atherosclerotic plaques with FDG-microPET: no FDG accumulation. Atherosclerosis 2007;192:275–82.PubMedCrossRefGoogle Scholar
  29. 29.
    Vallabhajosula S, Machac J, Knesaurek K. Imaging atherosclerotic macrophage density by positron emission tomography using F-18 fluorodeoxyglucose (FDG). J Nucl Med 1996;37:38.Google Scholar
  30. 30.
    Lederman RJ, Raylman RR, Fisher SJ, Kison PV, San H, Nabel EG, et al. Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG). Nucl Med Commun 2001;22:747–53.PubMedCrossRefGoogle Scholar
  31. 31.
    Watanabe Y. Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL-rabbit). Atherosclerosis 1980;36:261–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Zhang Z, Machac J, Helft G, Worthley SG, Tang C, Zaman AG, et al. Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation. BMC Nucl Med 2006;6:3.PubMedCrossRefGoogle Scholar
  33. 33.
    Theron J, Tyler JL. Takayasu’s arteritis of the aortic arch: endovascular treatment and correlation with positron emission tomography. AJNR Am J Neuroradiol 1987;8:621–6.PubMedGoogle Scholar
  34. 34.
    Mochizuki Y, Fujii H, Yasuda S, Nakahara T, Takahashi W, Ide M, et al. FDG accumulation in aortic walls. Clin Nucl Med 2001;26:68–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Yun M, Yeh D, Araujo LI, Jang S, Newberg A, Alavi A. F-18 FDG uptake in the large arteries: a new observation. Clin Nucl Med 2001;26:314–19.PubMedCrossRefGoogle Scholar
  36. 36.
    Yun M, Jang S, Cucchiara A, Newberg AB, Alavi A. 18F FDG uptake in the large arteries: a correlation study with the atherogenic risk factors. Semin Nucl Med 2002;32:70–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Tatsumi M, Cohade C, Nakamoto Y, Wahl RL. Fluorodeoxyglucose uptake in the aortic wall at PET/CT: possible finding for active atherosclerosis. Radiology 2003;229:831–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Ben-Haim S, Kupzov E, Tamir A, Israel O. Evaluation of 18F-FDG uptake and arterial wall calcifications using 18F-FDG PET/CT. J Nucl Med 2004;45:1816–21.PubMedGoogle Scholar
  39. 39.
    Bural GG, Torigian DA, Chamroonrat W, Houseni M, Chen W, Basu S, et al. FDG-PET is an effective imaging modality to detect and quantify age-related atherosclerosis in large arteries. Eur J Nucl Med Mol Imaging 2008;35:562–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Basu S, Zhuang H, Alavi A. Imaging of lower extremity artery atherosclerosis in diabetic foot: FDG-PET imaging and histopathological correlates. Clin Nucl Med 2007;32:567–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Tahara N, Kai H, Yamagishi S, Mizoguchi M, Nakaura H, Ishibashi M, et al. Vascular inflammation evaluated by [18F]-fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome. J Am Coll Cardiol 2007;49:1533–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Dunphy MP, Freiman A, Larson SM, Strauss HW. Association of vascular 18F-FDG uptake with vascular calcification. J Nucl Med 2005;46:1278–84.PubMedGoogle Scholar
  43. 43.
    Meller J, Strutz F, Siefker U, Scheel A, Sahlmann CO, Lehmann K, et al. Early diagnosis and follow-up of aortitis with [(18)F]FDG PET and MRI. Eur J Nucl Med Mol Imaging 2003;30:730–6.PubMedGoogle Scholar
  44. 44.
    Tahara N, Kai H, Nakaura H, Mizoguchi M, Ishibashi M, Kaida H, et al. The prevalence of inflammation in carotid atherosclerosis: analysis with fluorodeoxyglucose positron emission tomography. Eur Heart J 2007;28:2243–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Ben-Haim S, Kupzov E, Tamir A, Frenkel A, Israel O. Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on follow-up PET/CT studies. J Nucl Cardiol 2006;13:791–800.PubMedCrossRefGoogle Scholar
  46. 46.
    Weissberg PL. Noninvasive imaging of atherosclerosis: the biology behind the pictures. J Nucl Med 2004;45:1794–5.PubMedGoogle Scholar
  47. 47.
    Wu YW, Kao HL, Chen MF, Lee BC, Tseng WY, Jeng JS, et al. Characterization of plaques using 18F-FDG PET/CT in patients with carotid atherosclerosis and correlation with matrix metalloproteinase-1. J Nucl Med 2007;48:227–33.PubMedGoogle Scholar
  48. 48.
    Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, et al. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol 2006;48:1818–24.PubMedCrossRefGoogle Scholar
  49. 49.
    Tahara N, Kai H, Ishibashi M, Nakaura H, Kaida H, Baba K, et al. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 2006;48:1825–31.PubMedCrossRefGoogle Scholar
  50. 50.
    Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 2001;103:926–33.PubMedGoogle Scholar
  51. 51.
    Corti R, Fayad ZA, Fuster V, Worthley SG, Helft G, Chesebro J, et al. 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.PubMedCrossRefGoogle Scholar
  52. 52.
    Ogawa M, Magata Y, Kato T, Hatano K, Ishino S, Mukai T, et al. Application of 18F-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilization of vulnerable atherosclerotic plaques. J Nucl Med 2006;47:1845–50.PubMedGoogle Scholar
  53. 53.
    Arauz A, Hoyos L, Zenteno M, Mendoza R, Alexanderson E. Carotid plaque inflammation detected by 18F-fluorodeoxyglucose-positron emission tomography. Pilot study. Clin Neurol Neurosurg 2007;109:409–12.PubMedCrossRefGoogle Scholar
  54. 54.
    Paulmier B, Duet M, Khayat R, Pierquet-Ghazzar N, Laissy JP, Maunoury C, et al. Arterial wall uptake of fluorodeoxyglucose on PET imaging in stable cancer disease patients indicates higher risk for cardiovascular events. J Nucl Cardiol 2008;15:209–17.PubMedCrossRefGoogle Scholar
  55. 55.
    Bural GG, Torigian DA, Chamroonrat W, Alkhawaldeh K, Houseni M, El-Haddad G, et al. Quantitative assessment of the atherosclerotic burden of the aorta by combined FDG-PET and CT image analysis: a new concept. Nucl Med Biol 2006;33:1037–43.PubMedCrossRefGoogle Scholar
  56. 56.
    Rudd JH, Myers KS, Bansilal S, Machac J, Pinto CA, Tong C, et al. Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med 2008;49:871–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Wengen Chen
    • 1
  • Gonca G. Bural
    • 1
  • Drew A. Torigian
    • 1
  • Daniel J. Rader
    • 2
  • Abass Alavi
    • 1
    Email author
  1. 1.Division of Nuclear Medicine, Department of RadiologyHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Institute for Translational Medicine and Therapeutics and Cardiovascular Institute, School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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