Ner curvature of the aortic arch in 3 months old and 12?4 months old ApoE2/2 mice on a western diet. doi:10.1371/journal.pone.0057299.gMRI of Epigenetic Reader Domain Plaque Burden and Vessel Wall StiffnessFigure 4. Detection of atherosclerotic lesions in the aortic arch using USPIOs. T2* effects of USPIO were observed on the basis of the aortic arch 24 hours after i.v. contrast agent injection. CNR significantly inhibitor decreased from 2.161.3 before injection of contrast agent to 29.760.7, 24 hours after injection of micelles. The typical blooming effect by the USPIOs (arrow) was best observed in frontal views (B) of the aortic arch. C. CNR (C1) and delta CNR (C2) of both age groups before and 24 hours after USPIO injection. doi:10.1371/journal.pone.0057299.gFigure 5. Vessel wall chracteristics measured 23977191 by MRI. A. Diameter of the aortic arch in mm measured at end-diastole and end-systole measured in CINE MRI images from 3 months and 12 months old ApoE2/2 mice B. Distensibility of the aortic arch measured by the average maximal circumferential strain calculated for both age groups. doi:10.1371/journal.pone.0057299.gMRI of Plaque Burden and Vessel Wall StiffnessFigure 6. The effect of atorvastatin treatment on atherosclerotic plaques. A. CNR (A1) and DCNR (A2) of atherosclerotic plaques on the inner curvature of the aortic arch of 3 months old as well as 12?4 months old ApoE2/2 mice on a western diet with or without supplementation with atorvastatin after micelle injection. B. CNR (B1) and DCNR (B2) of atherosclerotic plaques on the inner curvature of the 
3 treatment groups after USPIO injection. C. Diameter of the aortic arch in mm measured at end-diastole and end-systole measured in CINE MRI images in all 3 ApoE2/2 treatment groups. D. Average maximum circumferential strain values of the 3 treatment groups. doi:10.1371/journal.pone.0057299.gMRI of Plaque Burden and Vessel Wall StiffnessFigure 7. Histological validation of atherosclerosis and MRI. A. Lipid depositions on the basis of the aortic arch and in the branches to the carotid and brachiocephalic arteries were shown by Oil Red O staining. B. Regions with atherosclerotic plaques corresponding to the regions in A are depicted in this MR image of the aortic arch. C. Plaque sizes of the 3 treatment groups in mm2 determined on histological slices. D. Anti-Gd-DTPA immunohistochemical DAB staining localized the micelles in atherosclerotic plaques. E. Iron deposits are visualized with Prussian blue enhanced with DAB in the wall of the aortic arch. F. Correlation CNR of atherosclerotic plaques on the inner curvature of the aortic arch (F1 micelles, F2 USPIO) with plaque sizes of the 3 groups determined on histological slices. G. Correlation of the aortic arch lesion area with the circumferential strain of the 3 treatment groups. H. Correlation of the CNR of both micelles (H1) as well as USPIO (H2) with the circumferential strain for all data-points together. doi:10.1371/journal.pone.0057299.g(Guerbet group, Aulnay sous Bois, France). An equivalent of 250 mmol Fe/kg bodyweight was injected i.v.MRI ProtocolsAll experiments were performed with a vertical 89-mm bore 9.4 T magnet (Bruker, Ettlingen, Germany) supplied with an actively shielded Micro2.5 gradient system of 1 T/m and a 30 mm transmit/receive birdcage RF coil, using Paravision 4.0 software. At the start of each examination, several 2D Fast Low Angle Shot (FLASH) scout images were recorded in the transverse and axial plane of the heart to determine the orientation.Ner curvature of the aortic arch in 3 months old and 12?4 months old ApoE2/2 mice on a western diet. doi:10.1371/journal.pone.0057299.gMRI of Plaque Burden and Vessel Wall StiffnessFigure 4. Detection of atherosclerotic lesions in the aortic arch using USPIOs. T2* effects of USPIO were observed on the basis of the aortic arch 24 hours after i.v. contrast agent injection. CNR significantly decreased from 2.161.3 before injection of contrast agent to 29.760.7, 24 hours after injection of micelles. The typical blooming effect by the USPIOs (arrow) was best observed in frontal views (B) of the aortic arch. C. CNR (C1) and delta CNR (C2) of both age groups before and 24 hours after USPIO injection. doi:10.1371/journal.pone.0057299.gFigure 5. Vessel wall chracteristics measured 23977191 by MRI. A. Diameter of the aortic arch in mm measured at end-diastole and end-systole measured in CINE MRI images from 3 months and 12 months old ApoE2/2 mice B. Distensibility of the aortic arch measured by the average maximal circumferential strain calculated for both age groups. doi:10.1371/journal.pone.0057299.gMRI of Plaque Burden and Vessel Wall StiffnessFigure 6. The effect of atorvastatin treatment on atherosclerotic plaques. A. CNR (A1) and DCNR (A2) of atherosclerotic plaques on the inner curvature of the aortic arch of 3 months old as well as 12?4 months old ApoE2/2 mice on a western diet with or without supplementation with atorvastatin after micelle injection. B. CNR (B1) and DCNR (B2) of atherosclerotic plaques on the inner curvature of the 3 treatment groups after USPIO injection. C. Diameter of the aortic arch in mm measured at end-diastole and end-systole measured in CINE MRI images in all 3 ApoE2/2 treatment groups. D. Average maximum circumferential strain values of the 3 treatment groups. doi:10.1371/journal.pone.0057299.gMRI of Plaque Burden and Vessel Wall StiffnessFigure 7. Histological validation of atherosclerosis and MRI. A. Lipid depositions on the basis of the aortic arch and in the branches to the carotid and brachiocephalic arteries were shown by Oil Red O staining. B. Regions with atherosclerotic plaques corresponding to the regions in A are depicted in this MR image of the aortic arch. C. Plaque sizes of the 3 treatment groups in 
mm2 determined on histological slices. D. Anti-Gd-DTPA immunohistochemical DAB staining localized the micelles in atherosclerotic plaques. E. Iron deposits are visualized with Prussian blue enhanced with DAB in the wall of the aortic arch. F. Correlation CNR of atherosclerotic plaques on the inner curvature of the aortic arch (F1 micelles, F2 USPIO) with plaque sizes of the 3 groups determined on histological slices. G. Correlation of the aortic arch lesion area with the circumferential strain of the 3 treatment groups. H. Correlation of the CNR of both micelles (H1) as well as USPIO (H2) with the circumferential strain for all data-points together. doi:10.1371/journal.pone.0057299.g(Guerbet group, Aulnay sous Bois, France). An equivalent of 250 mmol Fe/kg bodyweight was injected i.v.MRI ProtocolsAll experiments were performed with a vertical 89-mm bore 9.4 T magnet (Bruker, Ettlingen, Germany) supplied with an actively shielded Micro2.5 gradient system of 1 T/m and a 30 mm transmit/receive birdcage RF coil, using Paravision 4.0 software. At the start of each examination, several 2D Fast Low Angle Shot (FLASH) scout images were recorded in the transverse and axial plane of the heart to determine the orientation.