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Quantification of plaque lipids in the aortic root of ApoE-deficient mice by 3D DIXON magnetic resonance imaging in an ex vivo model

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Abstract

Objectives

To establish a dedicated protocol for the three-dimensional (3D) quantification of plaque lipids in apolipoprotein E-deficient (apoE−/−) mice using ex vivo MRI.

Methods

ApoE−/− mice were fed a high-fat diet (n = 10) or normal food (n = 10) for 3 months. Subsequently, a 3D FLASH MRI sequence was used to view the anatomy of the aortic root in the isolated hearts, where a 3D double-echo two-excitation pulse sequence (DIXON sequence) was used to selectively image plaque lipids. The vessel wall, lumen and plaque lipid volumes were quantified by MRI and histology for correlation analysis.

Results

DIXON MRI allowed visualisation and accurate quantification of plaque lipids. When comparing the vessel wall, lumen and plaque lipid sizes in the aortic root, Bland–Altman and linear regression analysis revealed a close correlation between MRI results and the histological data both on a slice-by-slice basis and of the volumetric measurements (vessel wall: r 2 = 0.775, p < 0.001; vessel lumen: r 2 = 0.875; p = 0.002; plaque lipid: r 2 = 0.819, p = 0.003).

Conclusions

The combination of 3D FLASH and DIXON-sequence MRI permits an accurate ex vivo assessment of the investigated plaque parameters in the aortic root of mice, particularly the lipid content.

Key Points

• Ex vivo MRI allows high resolution quantification of plaque parameters in mice

• DIXON MRI enables visualisation of plaque lipids in the aortic root of mice

• A close correlation between histology and MRI quantifies plaque parameters

• Preservation of tissue integrity allows additional analysis to be performed

• Short measurement time may permit the translation into in vivo measurements

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Abbreviations

3D:

Three-dimensional

apoE:

Apolipoprotein E

CCD:

Charge-coupled device

FLASH:

Fast low-angle shot

FOV:

Field of view

HS:

Histology

MRI:

Magnetic resonance imaging

NC:

Normal chow

RARE:

Rapid acquisition with refocused echoes

ROI:

Region of interest

TE:

Echo time

TR:

Repetition time

WD:

Western-type diet

References

  1. Zhang SH, Reddick RL, Piedrahita JA, Maeda N (1992) Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258:468–471

    Article  CAS  PubMed  Google Scholar 

  2. Wouters K, Shiri-Sverdlov R, van Gorp PJ, van Bilsen M, Hofker MH (2005) Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified apoe and ldlr mice. Clin Chem Lab Med 43:470–479

    Article  CAS  PubMed  Google Scholar 

  3. McAteer MA, Schneider JE, Clarke K, Neubauer S, Channon KM, Choudhury RP (2004) Quantification and 3D reconstruction of atherosclerotic plaque components in apolipoprotein E knockout mice using ex vivo high-resolution MRI. Arterioscler Thromb Vasc Biol 24:2384–2390

    Article  CAS  PubMed  Google Scholar 

  4. Schneider JE, McAteer MA, Tyler DJ et al (2004) High-resolution, multicontrast three-dimensional-MRI characterizes atherosclerotic plaque composition in ApoE-/- mice ex vivo. J Magn Reson Imaging 20:981–989

    Article  PubMed  Google Scholar 

  5. Alsaid H, Sabbah M, Bendahmane Z et al (2007) High-resolution contrast-enhanced MRI of atherosclerosis with digital cardiac and respiratory gating in mice. Magn Reson Med 58:1157–1163

    Article  PubMed  Google Scholar 

  6. Chaabane L, Pellet N, Bourdillon MC et al (2004) Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla. MAGMA 17:188–195

    Article  CAS  PubMed  Google Scholar 

  7. Choudhury RP, Fayad ZA, Aguinaldo JG et al (2003) Serial, noninvasive, in vivo magnetic resonance microscopy detects the development of atherosclerosis in apolipoprotein E-deficient mice and its progression by arterial wall remodeling. J Magn Reson Imaging 17:184–189

    Article  PubMed  Google Scholar 

  8. Dietrich T, Hucko T, Bourayou R et al (2009) High resolution magnetic resonance imaging in atherosclerotic mice treated with ezetimibe. Int J Cardiovasc Imaging 25:827–836

    Article  PubMed  Google Scholar 

  9. Fuster V, Stein B, Ambrose JA, Badimon L, Badimon JJ, Chesebro JH (1990) Atherosclerotic plaque rupture and thrombosis. Evolving concepts. Circulation 82:II47–II59

    CAS  PubMed  Google Scholar 

  10. Guyton JR, Klemp KF (1996) Development of the lipid-rich core in human atherosclerosis. Arterioscler Thromb Vasc Biol 16:4–11

    Article  CAS  PubMed  Google Scholar 

  11. Worthley SG, Helft G, Fuster V et al (2000) Noninvasive in vivo magnetic resonance imaging of experimental coronary artery lesions in a porcine model. Circulation 101:2956–2961

    Article  CAS  PubMed  Google Scholar 

  12. Worthley SG, Helft G, Fuster V et al (2000) Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis. Circulation 101:586–589

    Article  CAS  PubMed  Google Scholar 

  13. Phinikaridou A, Ruberg FL, Hallock KJ et al (2010) In vivo detection of vulnerable atherosclerotic plaque by MRI in a rabbit model. Circ Cardiovasc Imaging 3:323–332

    Article  PubMed  Google Scholar 

  14. Trogan E, Fayad ZA, Itskovich VV et al (2004) Serial studies of mouse atherosclerosis by in vivo magnetic resonance imaging detect lesion regression after correction of dyslipidemia. Arterioscler Thromb Vasc Biol 24:1714–1719

    Article  CAS  PubMed  Google Scholar 

  15. Nunnari JJ, Zand T, Joris I, Majno G (1989) Quantitation of oil red O staining of the aorta in hypercholesterolemic rats. Exp Mol Pathol 51:1–8

    Article  CAS  PubMed  Google Scholar 

  16. Hennig J, Nauerth A, Friedburg H (1986) RARE imaging: a fast imaging method for clinical MR. Magn Reson Med 3:823–833

    Article  CAS  PubMed  Google Scholar 

  17. Dixon WT (1984) Simple proton spectroscopic imaging. Radiology 153:189–194

    Article  CAS  PubMed  Google Scholar 

  18. Szumowski J, Coshow WR, Li F, Quinn SF (1994) Phase unwrapping in the three-point Dixon method for fat suppression MR imaging. Radiology 192:555–561

    Article  CAS  PubMed  Google Scholar 

  19. Fayad ZA, Fallon JT, Shinnar M et al (1998) Noninvasive in vivo high-resolution magnetic resonance imaging of atherosclerotic lesions in genetically engineered mice. Circulation 98:1541–1547

    Article  CAS  PubMed  Google Scholar 

  20. Itskovich VV, Choudhury RP, Aguinaldo JG et al (2003) Characterization of aortic root atherosclerosis in ApoE knockout mice: high-resolution in vivo and ex vivo MRM with histological correlation. Magn Reson Med 49:381–385

    Article  CAS  PubMed  Google Scholar 

  21. Sigovan M, Kaye E, Lancelot E et al (2012) Anti-inflammatory drug evaluation in ApoE-/- mice by ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging. Invest Radiol 47:546–552

    Article  CAS  PubMed  Google Scholar 

  22. Falk E (1992) Why do plaques rupture? Circulation 86:III30–III42

    CAS  PubMed  Google Scholar 

  23. Kolodgie FD, Burke AP, Farb A et al (2001) The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol 16:285–292

    Article  CAS  PubMed  Google Scholar 

  24. Virmani R, Burke AP, Farb A (1999) Plaque rupture and plaque erosion. Thromb Haemost 82:1–3

    PubMed  Google Scholar 

  25. Serfaty JM, Chaabane L, Tabib A, Chevallier JM, Briguet A, Douek PC (2001) Atherosclerotic plaques: classification and characterization with T2-weighted high-spatial-resolution MR imaging–an in vitro study. Radiology 219:403–410

    Article  CAS  PubMed  Google Scholar 

  26. Toussaint JF, Southern JF, Fuster V, Kantor HL (1995) T2-weighted contrast for NMR characterization of human atherosclerosis. Arterioscler Thromb Vasc Biol 15:1533–1542

    CAS  PubMed  Google Scholar 

  27. Morrisett J, Vick W, Sharma R et al (2003) Discrimination of components in atherosclerotic plaques from human carotid endarterectomy specimens by magnetic resonance imaging ex vivo. Magn Reson Imaging 21:465–474

    Article  PubMed  Google Scholar 

  28. Jellus V (2009) Phase correction method. US Patent Application US 2009/0201021. http://www.freepatentsonline.com/y2009/0201021.html

  29. Farrelly C, Shah S, Davarpanah A, Keeling AN, Carr JC (2012) ECG-gated multiecho Dixon fat-water separation in cardiac MRI: advantages over conventional fat-saturated imaging. AJR Am J Roentgenol 199:W74–W83

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Regina Altendorf for her exceptional technical assistance. The project was funded by the German Foundation of Heart Research (F/25/13) and the ELAN-fonds (M2-12-12-19-1) of the University of Erlangen-Nuremberg.

The scientific guarantor of this publication is Dr. Barbara Dietel. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. No complex statistical methods were necessary for this paper. Institutional review board approval was not required because it did not contain analysis of human tissue. Approval from the institutional animal care committee was obtained. Methodology: prospective, experimental, performed at one institution.

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Authors and Affiliations

  1. Department of Cardiology and Angiology, University Hospital of Erlangen-Nuremberg, Erlangen, Germany

    Barbara Dietel, Constanze Kuehn & Stephan Achenbach

  2. Campus Science Support Facilities (CSF), Vienna Biocenter (VBC), 1030, Vienna, Austria

    Lubos Budinsky

  3. Department of Radiology, University Hospital of Erlangen-Nuremberg, Erlangen, Germany

    Michael Uder

  4. Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany

    Andreas Hess

Authors
  1. Barbara Dietel
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  2. Lubos Budinsky
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  3. Constanze Kuehn
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  4. Michael Uder
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  5. Stephan Achenbach
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  6. Andreas Hess
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Correspondence to Barbara Dietel.

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Dietel, B., Budinsky, L., Kuehn, C. et al. Quantification of plaque lipids in the aortic root of ApoE-deficient mice by 3D DIXON magnetic resonance imaging in an ex vivo model. Eur Radiol 25, 736–744 (2015). https://doi.org/10.1007/s00330-014-3456-7

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  • DOI: https://doi.org/10.1007/s00330-014-3456-7

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