Abstract

BackgroundHigh-resolution contrast-enhanced imaging of the murine atherosclerotic vessel wall is difficult due to unpredictable flow artifacts, motion of the thin artery wall and problems with flow suppression in the presence of a circulating contrast agent.Methods and ResultsWe applied a 2D-FLASH retrospective-gated CINE MRI method at 9.4T to characterize atherosclerotic plaques and vessel wall distensibility in the aortic arch of aged ApoE−/− mice after injection of a contrast agent. The method enabled detection of contrast enhancement in atherosclerotic plaques in the aortic arch after I.V. injection of micelles and iron oxides resulting in reproducible plaque enhancement. Both contrast agents were taken up in the plaque, which was confirmed by histology. Additionally, the retrospective-gated CINE method provided images of the aortic wall throughout the cardiac cycle, from which the vessel wall distensibility could be calculated. Reduction in plaque size by statin treatment resulted in lower contrast enhancement and reduced wall stiffness.ConclusionsThe retrospective-gated CINE MRI provides a robust and simple way to detect and quantify contrast enhancement in atherosclerotic plaques in the aortic wall of ApoE−/− mice. From the same scan, plaque-related changes in stiffness of the aortic wall can be determined. In this mouse model, a correlation between vessel wall stiffness and atherosclerotic lesions was found.

Highlights

  • Cardiovascular diseases, in particular carotid and other peripheral atherosclerotic diseases are the leading causes of death in the western world [1]

  • In this report we describe the simultaneous determination of plaque burden in the aortic arch and the stiffness and distensibility of the vessel wall of mice using retrospective-gated CINE MRI

  • Optimal time points for contrast agent accumulation in the plaque were determined in a pilot time-course study with n = 8 mice per group in which contrast agent accumulation was followed over time for 7 days with intervals ranging from 30 minutes to 6 hours (Figure S1)

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Summary

Introduction

Cardiovascular diseases, in particular carotid and other peripheral atherosclerotic diseases are the leading causes of death in the western world [1]. Apart from the composition of atherosclerotic plaques, arterial stiffness and distensibility are independent predictor of cardiac morbidity Despite this independency, atherosclerotic plaques do contribute significantly to the vessel wall stiffness, and changes in plaque burden or aortic compliance could help to identify early cardiovascular disease in patients before an actual plaque rupture, as well as monitor the results of the therapeutic interventions [3,4]. Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are well known to exert beneficial effects on the elastic properties of the arterial wall [5]. They are widely applied in both the clinic as well as in preclinical studies. High-resolution contrast-enhanced imaging of the murine atherosclerotic vessel wall is difficult due to unpredictable flow artifacts, motion of the thin artery wall and problems with flow suppression in the presence of a circulating contrast agent

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