Despite the beneficial effect of percutaneous transluminal coronary angioplasty and stent implantation, these procedures may damage the vessel wall, particularly the endothelium leading to a dysfunctional state characterized by impaired vasodilation, increased vascular permeability and leukocyte infiltration that initiate atherosclerosis. The arterial system can be divided in “athero-susceptible” areas, e.g. arterial branches, where blood flow is turbulent and shear stress is multidirectional and “athero-resistant” areas, e.g. abdominal aorta, where blood flow is laminar and shear stress is low. Previous studies have shown that contrast-enhanced MRI using gadofosveset, an albumin-binding contrast agent, can detect endothelial damage, angiogenesis and vascular permeability in different animal models of vascular disease1-3. In this study, we sought to investigate the impact of endothelial injury in an “atherosclerotic-resistant” area and whether imaging with gadofosveset could be used to evaluate focal changes of vascular permeability and remodeling in-vivo.The study design is summarized in Figure 1. In-vivo MRI: A clinically approved albumin-binging contrast agent (gadofosveset) was used to assess focal changes in vascular permeability in three different groups of ApoE-/- mice; (1) 8-weeks-old male ApoE-/- mice were switched to high fat diet (containing 21% fat from lard and 0.15% (wt/wt) cholesterol), as an established model of hypercholesterolemia and atherosclerosis (n=6); (2) in the vascular injury group mice underwent endothelial denudation surgery3 and were switched to HFD following surgery (n=9); (3) in the treatment group, ApoE-/- mice underwent vascular injury followed by HFD and pravastatin treatment (40mg/kg/day) administered in drinking water (n=6). A subgroup of ApoE-/- mice (n=6) was imaged before intervention and HFD diet and used as controls. A 3T Philips Achieva system and a 47mm single loop microscopy surface coil were used. Images were acquired 30min after intravenous administration of 0.03mmol/kg gadofosveset. Phase-contrast-angiography images were acquired with a FOV=35x35x12mm, matrix=233x233, in-plane-resolution=0.15x0.15x0.5mm, TR/TE=28/6ms and flip angle=40°. 3D gradient-echo DE-MRI images were acquired with a FOV=35x35x12mm, matrix=348x348, in-plane-resolution=0.1x0.1x1mm, TR/TE=27/8ms, TR between subsequent IR pulses=1000ms, and flip angle=30°. T1 mapping was performed using 3D Look-Locker sequence that employs two non-selective inversion pulses with inversion times ranging from 20ms to 2000ms, followed by eight segmented readouts for eight individual images. The two imaging trains result in a set of 16 images per slice with increasing inversion times. The acquisition parameters were: FOV=36x22x10mm, matrix=180x102, in-plane-resolution=0.2x0.2x0.5mm, TR/TE=9/4.6ms, flip angle=10°. T1 values were computed on a pixel-by-pixel basis using in-house software algorithm (Matlab). Histology: BCA was stained with Masson’s trichrome to examine the vascular remodeling.Longitudinal DE-MRI using gadofosveset (Fig. 2) showed a significant progressive enhancement of the abdominal aorta in the injury group (Fig. 2E-G) compared to the HFD group (Fig. 2B-D). Importantly, there was decreased uptake in the treatment group, demonstrating the improvement that statins exert on vascular permeability (Fig. 2H). Very little uptake was detected in the baseline group (Fig. 2A). Histological images revealed advanced atherosclerosis in the injury group (Fig. 2J), less advanced disease in the treatment group (Fig. 2K) and no atherosclerosis in the HFD group (Fig. 2I) after 12 weeks. Quantitative analysis of vessel wall enhancement (Fig. 3A) and relaxation rate R1 (Fig. 3B) showed increased vascular permeability in the injury group 12 weeks after denudation as compared to HFD and treatment groups. No quantitative changes in the luminal area of the abdominal aorta were detected between groups (Fig. 3C) suggesting that luminal area is preserved in spite of increased vascular remodeling and plaque progression.In this study, we demonstrate that vascular injury together with dietary hyperlipidemia causes the formation of atherosclerotic lesions in an otherwise “atherosclerosis-resistant” segment of the aorta compared with hypercholesterolemia alone. The switch into an “atherosclerotic-susceptible” area is associated with increased vascular permeability that can be assessed in-vivo using the albumin binding MR contrast agent, gadofosveset.