Skip to main content
Erschienen in: European Radiology 3/2015

01.03.2015 | Experimental

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

verfasst von: Barbara Dietel, Lubos Budinsky, Constanze Kuehn, Michael Uder, Stephan Achenbach, Andreas Hess

Erschienen in: European Radiology | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

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
Literatur
1.
Zurück zum Zitat Zhang SH, Reddick RL, Piedrahita JA, Maeda N (1992) Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258:468–471CrossRefPubMed Zhang SH, Reddick RL, Piedrahita JA, Maeda N (1992) Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258:468–471CrossRefPubMed
2.
Zurück zum Zitat 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 43:470–479CrossRefPubMed 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 43:470–479CrossRefPubMed
3.
Zurück zum Zitat 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 24:2384–2390CrossRefPubMed 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 24:2384–2390CrossRefPubMed
4.
Zurück zum Zitat 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 20:981–989CrossRefPubMed 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 20:981–989CrossRefPubMed
5.
Zurück zum Zitat 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 58:1157–1163CrossRefPubMed 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 58:1157–1163CrossRefPubMed
6.
Zurück zum Zitat 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 17:188–195CrossRefPubMed 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 17:188–195CrossRefPubMed
7.
Zurück zum Zitat 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 17:184–189CrossRefPubMed 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 17:184–189CrossRefPubMed
8.
Zurück zum Zitat Dietrich T, Hucko T, Bourayou R et al (2009) High resolution magnetic resonance imaging in atherosclerotic mice treated with ezetimibe. Int J Cardiovasc Imaging 25:827–836CrossRefPubMed Dietrich T, Hucko T, Bourayou R et al (2009) High resolution magnetic resonance imaging in atherosclerotic mice treated with ezetimibe. Int J Cardiovasc Imaging 25:827–836CrossRefPubMed
9.
Zurück zum Zitat Fuster V, Stein B, Ambrose JA, Badimon L, Badimon JJ, Chesebro JH (1990) Atherosclerotic plaque rupture and thrombosis. Evolving concepts. Circulation 82:II47–II59PubMed Fuster V, Stein B, Ambrose JA, Badimon L, Badimon JJ, Chesebro JH (1990) Atherosclerotic plaque rupture and thrombosis. Evolving concepts. Circulation 82:II47–II59PubMed
10.
Zurück zum Zitat Guyton JR, Klemp KF (1996) Development of the lipid-rich core in human atherosclerosis. Arterioscler Thromb Vasc Biol 16:4–11CrossRefPubMed Guyton JR, Klemp KF (1996) Development of the lipid-rich core in human atherosclerosis. Arterioscler Thromb Vasc Biol 16:4–11CrossRefPubMed
11.
Zurück zum Zitat 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 101:2956–2961CrossRefPubMed 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 101:2956–2961CrossRefPubMed
12.
Zurück zum Zitat Worthley SG, Helft G, Fuster V et al (2000) Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis. Circulation 101:586–589CrossRefPubMed Worthley SG, Helft G, Fuster V et al (2000) Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis. Circulation 101:586–589CrossRefPubMed
13.
Zurück zum Zitat 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 3:323–332CrossRefPubMed 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 3:323–332CrossRefPubMed
14.
Zurück zum Zitat 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 24:1714–1719CrossRefPubMed 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 24:1714–1719CrossRefPubMed
15.
Zurück zum Zitat Nunnari JJ, Zand T, Joris I, Majno G (1989) Quantitation of oil red O staining of the aorta in hypercholesterolemic rats. Exp Mol Pathol 51:1–8CrossRefPubMed Nunnari JJ, Zand T, Joris I, Majno G (1989) Quantitation of oil red O staining of the aorta in hypercholesterolemic rats. Exp Mol Pathol 51:1–8CrossRefPubMed
16.
Zurück zum Zitat Hennig J, Nauerth A, Friedburg H (1986) RARE imaging: a fast imaging method for clinical MR. Magn Reson Med 3:823–833CrossRefPubMed Hennig J, Nauerth A, Friedburg H (1986) RARE imaging: a fast imaging method for clinical MR. Magn Reson Med 3:823–833CrossRefPubMed
18.
Zurück zum Zitat Szumowski J, Coshow WR, Li F, Quinn SF (1994) Phase unwrapping in the three-point Dixon method for fat suppression MR imaging. Radiology 192:555–561CrossRefPubMed Szumowski J, Coshow WR, Li F, Quinn SF (1994) Phase unwrapping in the three-point Dixon method for fat suppression MR imaging. Radiology 192:555–561CrossRefPubMed
19.
Zurück zum Zitat 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 98:1541–1547CrossRefPubMed 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 98:1541–1547CrossRefPubMed
20.
Zurück zum Zitat 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 49:381–385CrossRefPubMed 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 49:381–385CrossRefPubMed
21.
Zurück zum Zitat 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 47:546–552CrossRefPubMed 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 47:546–552CrossRefPubMed
22.
Zurück zum Zitat Falk E (1992) Why do plaques rupture? Circulation 86:III30–III42PubMed Falk E (1992) Why do plaques rupture? Circulation 86:III30–III42PubMed
23.
Zurück zum Zitat 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 16:285–292CrossRefPubMed 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 16:285–292CrossRefPubMed
24.
Zurück zum Zitat Virmani R, Burke AP, Farb A (1999) Plaque rupture and plaque erosion. Thromb Haemost 82:1–3PubMed Virmani R, Burke AP, Farb A (1999) Plaque rupture and plaque erosion. Thromb Haemost 82:1–3PubMed
25.
Zurück zum Zitat 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 219:403–410CrossRefPubMed 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 219:403–410CrossRefPubMed
26.
Zurück zum Zitat Toussaint JF, Southern JF, Fuster V, Kantor HL (1995) T2-weighted contrast for NMR characterization of human atherosclerosis. Arterioscler Thromb Vasc Biol 15:1533–1542PubMed Toussaint JF, Southern JF, Fuster V, Kantor HL (1995) T2-weighted contrast for NMR characterization of human atherosclerosis. Arterioscler Thromb Vasc Biol 15:1533–1542PubMed
27.
Zurück zum Zitat 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 21:465–474CrossRefPubMed 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 21:465–474CrossRefPubMed
29.
Zurück zum Zitat 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–W83CrossRefPubMed 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–W83CrossRefPubMed
Metadaten
Titel
Quantification of plaque lipids in the aortic root of ApoE-deficient mice by 3D DIXON magnetic resonance imaging in an ex vivo model
verfasst von
Barbara Dietel
Lubos Budinsky
Constanze Kuehn
Michael Uder
Stephan Achenbach
Andreas Hess
Publikationsdatum
01.03.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
European Radiology / Ausgabe 3/2015
Print ISSN: 0938-7994
Elektronische ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-014-3456-7

Weitere Artikel der Ausgabe 3/2015

European Radiology 3/2015 Zur Ausgabe

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

S3-Leitlinie zu Pankreaskrebs aktualisiert

23.04.2024 Pankreaskarzinom Nachrichten

Die Empfehlungen zur Therapie des Pankreaskarzinoms wurden um zwei Off-Label-Anwendungen erweitert. Und auch im Bereich der Früherkennung gibt es Aktualisierungen.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.