Abstract
The aim of this study was to investigate the feasibility of noninvasive monitoring of plaque burden in apolipoprotein E-deficient (ApoE-/-) mice by Gadospin F (GDF)-enhanced magnetic resonance imaging (MRI). Gadolinium uptake in plaques was controlled using transmission electron microscopy (TEM) and x-ray fluorescence (XRF) microscopy. To monitor the progression of atherosclerosis, ApoE-/- (n = 5) and wild-type (n = 2) mice were fed a Western diet and imaged at 5, 10, 15, and 20 weeks. Contrast-enhanced MRI was performed at 7 T Clinscan (Bruker, Ettlingen, Germany) before and 2 hours after intravenous injection of GDF (100 μmol/kg) to determine the blood clearance. Plaque size and contrast to noise ratio (CNR) were calculated for each time point using region of interest measurements to evaluate plaque progression. Following MRI, aortas were excised and GDF uptake was cross-validated by TEM and XRF microscopy. The best signal enhancement in aortic plaque was achieved 2 hours after application of GDF. No signal differences between pre- and postcontrast MRI were detectable in wild-type mice. We observed a gradual and considerable increase in plaque CNR and size for the different disease stages. TEM and XRF microscopy confirmed the localization of GDF within the plaque. GDF-enhanced MRI allows noninvasive and reliable estimation of plaque burden and monitoring of atherosclerotic progression in vivo.
Highlights
The aim of this study was to investigate the feasibility of noninvasive monitoring of plaque burden in apolipoprotein E–deficient (ApoE2/2) mice by Gadospin F (GDF)-enhanced magnetic resonance imaging (MRI)
Earlier and late contrast-enhanced MRIs revealed that 2 hours after intravenous application of GDF, the majority of the contrast agent was cleared from the blood, so the vessel lumen appeared dark on T1-weighted MRIs, as seen prior to injection (Figure 2)
To monitor disease progression by MRI, GDF was injected into five ApoE2/2 mice at four different time points on the high-fat diet (HFD) and images were taken before and 2 hours after GDF application
Summary
The aim of this study was to investigate the feasibility of noninvasive monitoring of plaque burden in apolipoprotein E–deficient (ApoE2/2) mice by Gadospin F (GDF)-enhanced magnetic resonance imaging (MRI). To monitor the progression of atherosclerosis, ApoE2/2 (n 5 5) and wild-type (n 5 2) mice were fed a Western diet and imaged at 5, 10, 15, and 20 weeks. GDF-enhanced MRI allows noninvasive and reliable estimation of plaque burden and monitoring of atherosclerotic progression in vivo. Recent improvements in conventional and molecular magnetic resonance imaging (MRI) proved to be a promising tool in allowing evaluation of plaque composition at the cellular and molecular levels, improving the discrimination between stable and vulnerable plaque.[5,6] In particular, contrast-enhanced MRI using extracellular gadolinium (Gd)-based contrast agents has shown promise for highlighting specific plaque components.[7,8]. Gadofluorine M (GDM; Bayer Schering Pharma AG, Berlin-Wedding, Germany) has been described as a reliable, noninvasive tool to identify and quantify plaque
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