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Monitoring Plaque Inflammation in Atherosclerotic Rabbits with an Iron Oxide (P904) and (18)F-FDG Using a Combined PET/MR Scanner

Overview

Overview

Journal Atherosclerosis

Publisher Elsevier

Specialty Cardiology & Vascular Diseases

Date 2013 Apr 16

PMID 23582588

Citations 22

Authors

Authors

A Millon

S D Dickson

A Klink

D Izquierdo-Garcia

J Bini

E Lancelot

S Ballet

P Robert

J Mateo de Castro

C Corot

Z A Fayad

Affiliations

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim of this study was to compare the ability of (18)F-FDG PET and iron contrast-enhanced MRI with a novel USPIO (P904) to assess change in plaque inflammation induced by atorvastatin and dietary change in a rabbit model of atherosclerosis using a combined PET/MR scanner.

Materials And Methods: Atherosclerotic rabbits underwent USPIO-enhanced MRI and (18)F-FDG PET in PET/MR hybrid system at baseline and were then randomly divided into a progression group (high cholesterol diet) and a regression group (chow diet and atorvastatin). Each group was scanned again 6 months after baseline imaging. R2* (i.e. 1/T2*) values were calculated pre/post P904 injection. (18)F-FDG PET data were analyzed by averaging the mean Standard Uptake Value (SUVmean) over the abdominal aorta. The in vivo imaging was then correlated with matched histological sections stained for macrophages.

Results: (18)F-FDG PET showed strong FDG uptake in the abdominal aorta and P904 injection revealed an increase in R2* values in the aortic wall at baseline. At 6 months, SUVmean values measured in the regression group showed a significant decrease from baseline (p = 0.015). In comparison, progression group values remained constant (p = 0.681). R2* values showed a similar decreasing trend in the regression group suggesting less USPIO uptake in the aortic wall. Correlations between SUVmean or Change in R2* value and macrophages density (RAM-11 staining) were good (R(2) = 0.778 and 0.707 respectively).

Conclusion: This experimental study confirms the possibility to combine two functional imaging modalities to assess changes in the inflammation of atherosclerotic plaques. (18)F-FDG-PET seems to be more sensitive than USPIO P904 to detect early changes in plaque inflammation.

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References

1.

Worthley S, Zhang Z, Machac J, Helft G, Tang C, Liew G . In vivo non-invasive serial monitoring of FDG-PET progression and regression in a rabbit model of atherosclerosis. Int J Cardiovasc Imaging. 2008; 25(3):251-7. DOI: 10.1007/s10554-008-9377-2. View

2.

Briley-Saebo K, Mani V, Hyafil F, Cornily J, Fayad Z . Fractionated Feridex and positive contrast: in vivo MR imaging of atherosclerosis. Magn Reson Med. 2008; 59(4):721-30. DOI: 10.1002/mrm.21541. View

3.

Hyafil F, Vucic E, Cornily J, Sharma R, Amirbekian V, Blackwell F . Monitoring of arterial wall remodelling in atherosclerotic rabbits with a magnetic resonance imaging contrast agent binding to matrix metalloproteinases. Eur Heart J. 2010; 32(12):1561-71. PMC: 3114094. DOI: 10.1093/eurheartj/ehq413. View

4.

te Boekhorst B, Bovens S, Nederhoff M, van de Kolk K, Cramer M, van Oosterhout M . Negative MR contrast caused by USPIO uptake in lymph nodes may lead to false positive observations with in vivo visualization of murine atherosclerotic plaque. Atherosclerosis. 2009; 210(1):122-9. DOI: 10.1016/j.atherosclerosis.2009.10.036. View

5.

Sukhova G, Williams J, Libby P . Statins reduce inflammation in atheroma of nonhuman primates independent of effects on serum cholesterol. Arterioscler Thromb Vasc Biol. 2002; 22(9):1452-8. DOI: 10.1161/01.atv.0000030360.72503.56. View

6.

Folco E, Sheikine Y, Rocha V, Christen T, Shvartz E, Sukhova G . Hypoxia but not inflammation augments glucose uptake in human macrophages: Implications for imaging atherosclerosis with 18fluorine-labeled 2-deoxy-D-glucose positron emission tomography. J Am Coll Cardiol. 2011; 58(6):603-14. DOI: 10.1016/j.jacc.2011.03.044. View

7.

Wu Y, Kao H, Huang C, Chen M, Lin L, Wang Y . The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers. Eur J Nucl Med Mol Imaging. 2011; 39(3):399-407. DOI: 10.1007/s00259-011-1994-7. View

8.

Kooi M, Cappendijk V, Cleutjens K, Kessels A, Kitslaar P, Borgers M . Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation. 2003; 107(19):2453-8. DOI: 10.1161/01.CIR.0000068315.98705.CC. View

9.

Ouimet T, Lancelot E, Hyafil F, Rienzo M, Deux F, Lemaitre M . Molecular and cellular targets of the MRI contrast agent P947 for atherosclerosis imaging. Mol Pharm. 2012; 9(4):850-61. DOI: 10.1021/mp2003863. View

10.

Derlin T, Habermann C, Hahne J, Apostolova I, Klutmann S, Mester J . Quantification of [18F]-FDG uptake in atherosclerotic plaque: impact of renal function. Ann Nucl Med. 2011; 25(8):586-91. DOI: 10.1007/s12149-011-0503-1. View

11.

Izquierdo-Garcia D, Davies J, Graves M, Rudd J, Gillard J, Weissberg P . 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. 2008; 40(1):86-93. DOI: 10.1161/STROKEAHA.108.521393. View

12.

Briley-Saebo K, Cho Y, Shaw P, Ryu S, Mani V, Dickson S . Targeted iron oxide particles for in vivo magnetic resonance detection of atherosclerotic lesions with antibodies directed to oxidation-specific epitopes. J Am Coll Cardiol. 2010; 57(3):337-47. PMC: 3095034. DOI: 10.1016/j.jacc.2010.09.023. View

13.

Lobatto M, Calcagno C, Metselaar J, Storm G, Stroes E, Fayad Z . Imaging the efficacy of anti-inflammatory liposomes in a rabbit model of atherosclerosis by non-invasive imaging. Methods Enzymol. 2012; 508:211-28. PMC: 3612346. DOI: 10.1016/B978-0-12-391860-4.00011-2. View

14.

Tang T, Howarth S, Miller S, Graves M, U-King-Im J, Li Z . Correlation of carotid atheromatous plaque inflammation using USPIO-enhanced MR imaging with degree of luminal stenosis. Stroke. 2008; 39(7):2144-7. DOI: 10.1161/STROKEAHA.107.504753. View

15.

Amirbekian V, Lipinski M, Briley-Saebo K, Amirbekian S, Aguinaldo J, Weinreb D . Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. Proc Natl Acad Sci U S A. 2007; 104(3):961-6. PMC: 1766334. DOI: 10.1073/pnas.0606281104. View

16.

Kuhlpeter R, Dahnke H, Matuszewski L, Persigehl T, von Wallbrunn A, Allkemper T . R2 and R2* mapping for sensing cell-bound superparamagnetic nanoparticles: in vitro and murine in vivo testing. Radiology. 2007; 245(2):449-57. DOI: 10.1148/radiol.2451061345. View

17.

Sigovan M, Boussel L, Sulaiman A, Sappey-Marinier D, Alsaid H, Desbleds-Mansard C . Rapid-clearance iron nanoparticles for inflammation imaging of atherosclerotic plaque: initial experience in animal model. Radiology. 2009; 252(2):401-9. DOI: 10.1148/radiol.2522081484. View

18.

Rudd J, Myers K, Bansilal S, Machac J, Pinto C, Tong C . Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med. 2008; 49(6):871-8. DOI: 10.2967/jnumed.107.050294. View

19.

Zhou G, Ge S, Liu D, Xu G, Zhang R, Yin Q . Atorvastatin reduces plaque vulnerability in an atherosclerotic rabbit model by altering the 5-lipoxygenase pathway. Cardiology. 2010; 115(3):221-8. DOI: 10.1159/000296017. View

20.

Puato M, Faggin E, Rattazzi M, Zambon A, Cipollone F, Grego F . Atorvastatin reduces macrophage accumulation in atherosclerotic plaques: a comparison of a nonstatin-based regimen in patients undergoing carotid endarterectomy. Stroke. 2010; 41(6):1163-8. DOI: 10.1161/STROKEAHA.110.580811. View