High-resolution imaging of human atherosclerotic carotid plaques with micro18F-FDG PET scanning exploring plaque vulnerability
FDG-PET can be used to identify vulnerable plaques in atherosclerotic disease. Clinical FDG-PET camera systems are restricted in terms of resolution for the visualization of detailed inflammation patterns in smaller vascular structures. The aim of the study is to evaluate the possible added value of a high-resolution microPET system in excised carotid plaques using FDG.
Methods and Results
In this study, 17 patients with planned carotid endarterectomy were included. Excised plaques were incubated in FDG and subsequently imaged with microPET. Macrophage presence in plaques was evaluated semi-quantitatively by immunohistochemistry. Plaque calcification was assessed additionally with CT and correlated to FDG uptake. Finally, FDG uptake and macrophage infiltration were compared with patient symptomatology. Heterogeneous distributions and variable intensities of FDG uptake were found within the plaques. A positive correlation between the distribution of macrophages and the FDG uptake (r = 0.68, P < .01) was found. A negative correlation was found between areas of calcifications and FDG uptake (r = −0.84, P < .001). Ratio FDGmax values as well as degree of CD68 accumulation were significantly higher in CVA patients compared with TIA or amaurosis fugax patients (P < .05) and CVA patients compared with asymptomatic patients (P < .05).
This ex vivo study demonstrates that excised carotid plaques can be visualized in detail using FDG microPET. Enhancement of clinical PET/CT resolution for similar imaging results in patients is needed.
- Izquierdo-Garcia D, Davies JR, Graves MJ, Rudd JH, Gillard JH, Weissberg PL, et al. 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 2009;40:86-93. CrossRef
- Chaturvedi S, Bruno A, Feasby T, Holloway R, Benavente O, Cohen SN, et al. Carotid endarterectomy—an evidence-based review: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2005;65:794-801. CrossRef
- Wallis de Vries BM, van Dam GM, Tio RA, Hillebrands JL, Slart RH, Zeebregts CJ. Current imaging modalities to visualize vulnerability within the atherosclerotic carotid plaque. J Vasc Surg 2008;48:1620-9. CrossRef
- Chen W, Bural GG, Torigian DA, Rader DJ, Alavi A. Emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries. Eur J Nucl Med Mol Imaging 2009;36:144-51. CrossRef
- Jander S, Sitzer M, Schumann R, Schroeter M, Siebler M, Steinmetz H, et al. Inflammation in high-grade carotid stenosis: A possible role for macrophages and T cells in plaque destabilization. Stroke 1998;29:1625-30. CrossRef
- Fifer KM, Qadir S, Subramanian S, Vijayakumar J, Figueroa AL, Truong QA, et al. Positron emission tomography measurement of periodontal (18)f-fluorodeoxyglucose uptake is associated with histologically determined carotid plaque inflammation. J Am Coll Cardiol 2011;57:971-6. CrossRef
- 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.
- 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. CrossRef
- Rudd JH, Myers KS, Bansilal S, Machac J, Woodward M, Fuster V, et al. Relationships among regional arterial inflammation, calcification, risk factors, and biomarkers: A prospective fluorodeoxyglucose positron-emission tomography/computed tomography imaging study. Circ Cardiovasc Imaging 2009;2:107-15. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- Meerwaldt R, Slart RH, van Dam GM, Luijckx GJ, Tio RA, Zeebregts CJ. PET/SPECT imaging: From carotid vulnerability to brain viability. Eur J Radiol 2010;74:104-9. CrossRef
- Okane K, Ibaraki M, Toyoshima H, Sugawara S, Takahashi K, Miura S, et al. 18F-FDG accumulation in atherosclerosis: Use of CT and MR co-registration of thoracic and carotid arteries. Eur J Nucl Med Mol Imaging 2006;33:589-94. CrossRef
- Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 2009;50:1611-20. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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.
- Graebe M, Pedersen SF, Borgwardt L, Hojgaard L, Sillesen H, Kjaer A. Molecular pathology in vulnerable carotid plaques: Correlation with -fluorodeoxyglucose positron emission tomography (FDG-PET). Eur J Vasc Endovasc Surg 2009;37:714-21. CrossRef
- Sheikine Y, Akram K. FDG-PET imaging of atherosclerosis: Do we know what we see? Atherosclerosis 2010;211:371-80. CrossRef
- North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445-53.
- European Carotid Surgery Trialists' Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: Final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351(9113):1379-87.
- Becker CR, Kleffel T, Crispin A, Knez A, Young J, Schoepf UJ, et al. Coronary artery calcium measurement: Agreement of multirow detector and electron beam CT. AJR Am J Roentgenol 2001;176:1295-8.
- Hamacher K, Coenen HH, Stocklin G. Efficient stereospecific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med 1986;27:235-8.
- Hellings WE, Pasterkamp G, Vollebregt A, Seldenrijk CA, de Vries JP, Velema E, et al. Intraobserver and interobserver variability and spatial differences in histologic examination of carotid endarterectomy specimens. J Vasc Surg 2007;46:1147-54. CrossRef
- Rudd JH, Narula J, Strauss HW, Virmani R, Machac J, Klimas M, et al. Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: Ready for prime time? J Am Coll Cardiol 2010;55:2527-35. CrossRef
- Graebe M, Pedersen SF, Hojgaard L, Kjaer A, Sillesen H. 18FDG PET and ultrasound echolucency in carotid artery plaques. JACC Cardiovasc Imaging 2010;3:289-95. CrossRef
- Davies JR, Izquierdo-Garcia D, Rudd JH, Figg N, Richards HK, Bird JL, et al. FDG-PET can distinguish inflamed from non-inflamed plaque in an animal model of atherosclerosis. Int J Cardiovasc Imaging 2010;26:41-8. CrossRef
- Calder PC, Dimitriadis G, Newsholme P. Glucose metabolism in lymphoid and inflammatory cells and tissues. Curr Opin Clin Nutr Metab Care 2007;10:531-40. CrossRef
- Kietselaer BL, Reutelingsperger CP, Heidendal GA, Daemen MJ, Mess WH, Hofstra L, et al. Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis. N Engl J Med 2004;350:1472-3. CrossRef
- Font MA, Fernandez A, Carvajal A, Gamez C, Badimon L, Slevin M, et al. Imaging of early inflammation in low-to-moderate carotid stenosis by 18-FDG-PET. Front Biosci 2009;14:3352-60. CrossRef
- 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. CrossRef
- 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.
- Dunphy MP, Freiman A, Larson SM, Strauss HW. Association of vascular 18F-FDG uptake with vascular calcification. J Nucl Med 2005;46:1278-84.
- Kwee RM, van Oostenbrugge RJ, Hofstra L, Teule GJ, van Engelshoven JM, Mess WH, et al. Identifying vulnerable carotid plaques by noninvasive imaging. Neurology 2008;70:2401-9. CrossRef
- Laitinen I, Marjamaki P, Haaparanta M, Savisto N, Laine VJ, Soini SL, et al. Non-specific binding of [18F]FDG to calcifications in atherosclerotic plaques: Experimental study of mouse and human arteries. Eur J Nucl Med Mol Imaging 2006;33:1461-7. CrossRef
- Silvera SS, Aidi HE, Rudd JH, Mani V, Yang L, Farkouh M, et al. Multimodality imaging of atherosclerotic plaque activity and composition using FDG-PET/CT and MRI in carotid and femoral arteries. Atherosclerosis 2009;207:139-43. CrossRef
- Williams G, Kolodny GM. Retrospective study of coronary uptake of 18F-fluorodeoxyglucose in association with calcification and coronary artery disease: A preliminary study. Nucl Med Commun 2009;30:287-91. CrossRef
- 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. CrossRef
- 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. CrossRef
- High-resolution imaging of human atherosclerotic carotid plaques with micro18F-FDG PET scanning exploring plaque vulnerability
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Journal of Nuclear Cardiology
Volume 18, Issue 6 , pp 1066-1075
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- carotid artery
- vulnerable plaque
- Industry Sectors
- Marleen G. Masteling MSc (1)
- Clark J. Zeebregts MD, PhD (2) (3)
- René A. Tio MD, PhD (3) (4)
- Jan-Cees Breek MD, PhD (5)
- Uwe J. F. Tietge PhD (6)
- Jan Freark de Boer BSc (6)
- Andor W. J. M. Glaudemans MD (7)
- Rudi A. J. O. Dierckx MD, PhD (7)
- Hendrikus H. Boersma PharmD, PhD (3) (7) (8)
- Riemer H. J. A. Slart MD, PhD (3) (7)
- Author Affiliations
- 1. Faculty of Medicine, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands
- 2. Division of Vascular Surgery, Department of Surgery, University Medical Center Groningen (UMCG), University of Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands
- 3. Cardiovascular Imaging Group Groningen, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands
- 4. Department of Cardiology, Thorax Center, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands
- 5. Department of Surgery, Martini Hospital, Groningen, The Netherlands
- 6. Department of Pediatrics, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands
- 7. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands
- 8. Department of Hospital and Clinical Pharmacy, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands