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Published in: The International Journal of Cardiovascular Imaging 1/2010

01-01-2010 | Original Paper

FDG–PET can distinguish inflamed from non-inflamed plaque in an animal model of atherosclerosis

Authors: John R. Davies, David Izquierdo-Garcia, James H. F. Rudd, Nichola Figg, Hugh K. Richards, Joseph L. E. Bird, Franklin I. Aigbirhio, Anthony P. Davenport, Peter L. Weissberg, Tim D. Fryer, Elizabeth A. Warburton

Published in: The International Journal of Cardiovascular Imaging | Issue 1/2010

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Abstract

The presence of activated macrophages is an important predictor of atherosclerotic plaque rupture. In this study, our aim was to determine the accuracy of 18F- fluorodeoxyglucose (FDG) microPET imaging for quantifying aortic wall macrophage content in a rabbit model of atherosclerosis. Rabbits were divided into a control group and two groups post aortic balloon injury: 6 months high-cholesterol diet (HC); and 3 months HC followed by 3 months low-cholesterol diet plus statin (LCS). In vivo and ex vivo microPET, ex vivo well counting and histological quantification of the atherosclerotic aortas were performed for all groups. Macrophage density was greater in the HC group than the LCS group (5.1 ± 1.4% vs. 0.6 ± 0.7%, P < 0.001) with a trend towards greater macrophage density in LCS compared to controls (P = 0.08). There was a strong correlation across all groups between macrophage density and standardized uptake value (SUV) derived from ex vivo microPET (r = 0.95, P < 0.001) and well counting (r = 0.96, P < 0.001). Ex vivo FDG SUV was significantly different between the three groups (P < 0.001). However, the correlation between in vivo microPET FDG SUV and macrophage density was insignificant (r = 0.16, P = 0.57) with no statistical differences in FDG SUV seen between the three groups. This study confirms that in an animal model of inflamed and non-inflamed atherosclerosis, significant differences in FDG SUV allow differentiation of highly inflamed atherosclerotic aortas from those stabilized by statin therapy and low cholesterol diet and controls.
Literature
1.
go back to reference Virmani R, Burke AP, Farb A, Kolodgie FD (2006) Pathology of the vulnerable plaque. J Am Coll Cardiol 47:C13–C18CrossRefPubMed Virmani R, Burke AP, Farb A, Kolodgie FD (2006) Pathology of the vulnerable plaque. J Am Coll Cardiol 47:C13–C18CrossRefPubMed
2.
go back to reference Davies MJ, Thomas AC (1985) Plaque fissuring—the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 53:363–373CrossRefPubMed Davies MJ, Thomas AC (1985) Plaque fissuring—the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 53:363–373CrossRefPubMed
3.
go back to reference Ben-Haim S, Kupzov E, Tamir A, Israel O (2004) Evaluation of 18F-FDG uptake and arterial wall calcifications using 18F-FDG PET/CT. J Nucl Med 45:1816–1821PubMed Ben-Haim S, Kupzov E, Tamir A, Israel O (2004) Evaluation of 18F-FDG uptake and arterial wall calcifications using 18F-FDG PET/CT. J Nucl Med 45:1816–1821PubMed
4.
go back to reference Rudd JHF, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, Johnstrom P, Davenport AP, Kirkpatrick PJ, Arch BN, Pickard JD, Weissberg PL (2002) Imaging atherosclerotic plaque inflammation with 18F-fluorodeoxyglucose positron emission tomography. Circulation 105:2708–2711CrossRefPubMed Rudd JHF, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, Johnstrom P, Davenport AP, Kirkpatrick PJ, Arch BN, Pickard JD, Weissberg PL (2002) Imaging atherosclerotic plaque inflammation with 18F-fluorodeoxyglucose positron emission tomography. Circulation 105:2708–2711CrossRefPubMed
5.
go back to reference Davies JR, Rudd JHF, Fryer TD, Graves MJ, Clark JC, Kirkpatrick PJ, Gillard JH, Warburton EA, Weissberg PL (2005) Identification of culprit lesions after transient ischemic attack by combined 18F-fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging. Stroke 36:2642–2647CrossRefPubMed Davies JR, Rudd JHF, Fryer TD, Graves MJ, Clark JC, Kirkpatrick PJ, Gillard JH, Warburton EA, Weissberg PL (2005) Identification of culprit lesions after transient ischemic attack by combined 18F-fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging. Stroke 36:2642–2647CrossRefPubMed
6.
go back to reference Okane K, Ibaraki M, Toyoshima H, Sugawara S, Takahashi K, Miura S, Shimosegawa E, Kitamur J, Satoh T (2006) 18F-FDG accumulation in atherosclerosis: use of CT and MR co-registration of thoracic and carotid arteries. Eur J Nucl Med Mol Imaging 33:589–594CrossRefPubMed Okane K, Ibaraki M, Toyoshima H, Sugawara S, Takahashi K, Miura S, Shimosegawa E, Kitamur J, Satoh T (2006) 18F-FDG accumulation in atherosclerosis: use of CT and MR co-registration of thoracic and carotid arteries. Eur J Nucl Med Mol Imaging 33:589–594CrossRefPubMed
7.
go back to reference Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, Yates D, LaMuraglia GM, Furie K, Houser S, Gewirtz H, Muller JE, Brady TJ, Fischman AJ (2006) In vivo 18F-Fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol 48:1818–1824CrossRefPubMed Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, Yates D, LaMuraglia GM, Furie K, Houser S, Gewirtz H, Muller JE, Brady TJ, Fischman AJ (2006) In vivo 18F-Fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol 48:1818–1824CrossRefPubMed
8.
go back to reference Dunphy MP, Schoder H, Strauss HW (2007) Radionuclide techniques for identifying vulnerable plaque. J Nucl Med 48:1753–1755CrossRefPubMed Dunphy MP, Schoder H, Strauss HW (2007) Radionuclide techniques for identifying vulnerable plaque. J Nucl Med 48:1753–1755CrossRefPubMed
9.
go back to reference Dunphy MP, Freiman A, Larson SM, Strauss HW (2005) Association of vascular 18F-FDG uptake with vascular calcification. J Nucl Med 46:1278–1284PubMed Dunphy MP, Freiman A, Larson SM, Strauss HW (2005) Association of vascular 18F-FDG uptake with vascular calcification. J Nucl Med 46:1278–1284PubMed
11.
go back to reference Rudd JH, Hyafil F, Fayad ZA (2009) Inflammation imaging in atherosclerosis. Arterioscler Thromb Vasc Biol 29:1009–1016CrossRefPubMed Rudd JH, Hyafil F, Fayad ZA (2009) Inflammation imaging in atherosclerosis. Arterioscler Thromb Vasc Biol 29:1009–1016CrossRefPubMed
12.
go back to reference Lederman RJ, Raylman RR, Fisher SJ, Kison PV, San H, Nabel EG, Wahl RL (2001) Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG). Nucl Med Commun 22:747–753CrossRefPubMed Lederman RJ, Raylman RR, Fisher SJ, Kison PV, San H, Nabel EG, Wahl RL (2001) Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG). Nucl Med Commun 22:747–753CrossRefPubMed
13.
go back to reference Ogawa M, Ishino S, Mukai T, Asano D, Teramoto N, Watabe H, Kudomi N, Shiomi M, Magata Y, Iida H, Saji H (2004) 18F-FDG accumulation in athorosclerotic plaques: immunohistochemical and PET imaging study. J Nucl Med 45:1245–1250PubMed Ogawa M, Ishino S, Mukai T, Asano D, Teramoto N, Watabe H, Kudomi N, Shiomi M, Magata Y, Iida H, Saji H (2004) 18F-FDG accumulation in athorosclerotic plaques: immunohistochemical and PET imaging study. J Nucl Med 45:1245–1250PubMed
14.
go back to reference Ogawa M, Magata Y, Kato T, Hatano K, Ishino S, Mukai T, Shiomi M, Ito K, Saji H (2006) Application of 18F-FDG PET for monitoring the therapeutic effect of antiiflammatory drugs on stabilization of vulnerable atherosclerotic plaques. J Nucl Med 47:1845–1850PubMed Ogawa M, Magata Y, Kato T, Hatano K, Ishino S, Mukai T, Shiomi M, Ito K, Saji H (2006) Application of 18F-FDG PET for monitoring the therapeutic effect of antiiflammatory drugs on stabilization of vulnerable atherosclerotic plaques. J Nucl Med 47:1845–1850PubMed
15.
go back to reference Tawakol A, Migrino RQ, Hoffmann U, Abbara S, Houser S, Gewirtz H, Muller JE, Brady TJ, Fischman AJ (2005) Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. J Nucl Cardiol 12:294–301CrossRefPubMed Tawakol A, Migrino RQ, Hoffmann U, Abbara S, Houser S, Gewirtz H, Muller JE, Brady TJ, Fischman AJ (2005) Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. J Nucl Cardiol 12:294–301CrossRefPubMed
16.
go back to reference Zhang Z, Machac J, Helft G, Worthley SG, Tang C, Zaman AG, Rodriguez OJ, Buchsbaum MS, Fuster V, Badimon JJ (2006) Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation. BMC Nucl Med 6:4CrossRef Zhang Z, Machac J, Helft G, Worthley SG, Tang C, Zaman AG, Rodriguez OJ, Buchsbaum MS, Fuster V, Badimon JJ (2006) Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation. BMC Nucl Med 6:4CrossRef
17.
go back to reference Izquierdo-Garcia D, Davies JR, Graves MJ, Rudd JH, Gillard JH, Weissberg PL, Fryer TD, Warburton EA (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 40:86–93CrossRefPubMed Izquierdo-Garcia D, Davies JR, Graves MJ, Rudd JH, Gillard JH, Weissberg PL, Fryer TD, Warburton EA (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 40:86–93CrossRefPubMed
18.
go back to reference Rudd JH, Myers KS, Bansilal S, Machac J, Pinto CA, Tong C, Rafique A, Hargeaves R, Farkouh M, Fuster V, Fayad ZA (2008) Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med 49:871–878CrossRefPubMed Rudd JH, Myers KS, Bansilal S, Machac J, Pinto CA, Tong C, Rafique A, Hargeaves R, Farkouh M, Fuster V, Fayad ZA (2008) Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med 49:871–878CrossRefPubMed
19.
go back to reference Rudd JH, Myers KS, Bansilal S, Machac J, Rafique A, Farkouh M, Fuster V, Fayad ZA (2007) 18Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol 50:892–896CrossRefPubMed Rudd JH, Myers KS, Bansilal S, Machac J, Rafique A, Farkouh M, Fuster V, Fayad ZA (2007) 18Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol 50:892–896CrossRefPubMed
20.
go back to reference Fischman AJ, Lees AM, Lees RS, Barlai-Kovach M, Strauss HW (1987) Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall. Arteriosclerosis 7:361–366PubMed Fischman AJ, Lees AM, Lees RS, Barlai-Kovach M, Strauss HW (1987) Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall. Arteriosclerosis 7:361–366PubMed
21.
go back to reference Kinahan PE, Rogers JG (1989) Analytic 3D image reconstruction using all detected events. IEEE Trans Nucl Sci 36:964–968CrossRef Kinahan PE, Rogers JG (1989) Analytic 3D image reconstruction using all detected events. IEEE Trans Nucl Sci 36:964–968CrossRef
22.
go back to reference Patlak CS, Blasberg RG (1985) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab 5:584–590PubMed Patlak CS, Blasberg RG (1985) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab 5:584–590PubMed
23.
go back to reference Lehr HA, van der Loos CM, Teeling P, Gown AM (1999) Complete chromogen separation and analysis in double immunohistochemical stains using Photoshop-based image analysis. J Histochem Cytochem 47:119–126PubMed Lehr HA, van der Loos CM, Teeling P, Gown AM (1999) Complete chromogen separation and analysis in double immunohistochemical stains using Photoshop-based image analysis. J Histochem Cytochem 47:119–126PubMed
Metadata
Title
FDG–PET can distinguish inflamed from non-inflamed plaque in an animal model of atherosclerosis
Authors
John R. Davies
David Izquierdo-Garcia
James H. F. Rudd
Nichola Figg
Hugh K. Richards
Joseph L. E. Bird
Franklin I. Aigbirhio
Anthony P. Davenport
Peter L. Weissberg
Tim D. Fryer
Elizabeth A. Warburton
Publication date
01-01-2010
Publisher
Springer Netherlands
Published in
The International Journal of Cardiovascular Imaging / Issue 1/2010
Print ISSN: 1569-5794
Electronic ISSN: 1875-8312
DOI
https://doi.org/10.1007/s10554-009-9506-6

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