Predictive mouse model reflects distinct stages of human atheroma in a single carotid artery

Abstract

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Development of Molecular Magnetic Resonance Imaging Tools for Longitudinal Tracking of Carotid Atherosclerotic Disease Using Fast Imaging with Steady-State Precession

“…All animal experiments were approved by the Institutional Animal Care and Use Committee for Biological Resource Centre at A*STAR, Singapore (IACUC #191,459). ApoE −/− mice (Taconic Biosciences) were used to develop the carotid atherosclerosis model by means of cuff implantation as previously described [7,8,10,11]. The shear-stress modifying cuff induced development of vulnerable, inflamed plaques in the low shear-stress region upstream of cuff placement [7,8,[10][11][12].…”

“…ApoE −/− mice (Taconic Biosciences) were used to develop the carotid atherosclerosis model by means of cuff implantation as previously described [7,8,10,11]. The shear-stress modifying cuff induced development of vulnerable, inflamed plaques in the low shear-stress region upstream of cuff placement [7,8,[10][11][12]. ApoE −/− mice commenced on a high fat diet (HFD) 2 weeks prior to cuff placement.…”

“…A region of interest (ROI) was selected in the carotid arteries for axial imaging using steadystate GRE sequences. The ROI was placed in the lower half of carotid arteries based on the high prevalence of high-risk vulnerable plaques developed in that region as atherosclerosis progresses, validated in our previous work [10]. Once identified, baseline pre-contrast fast imaging with steady-state precession (FISP) sequence was performed: TR, 9.2 ms; TE, 4.6 ms; FOV, 25 × 25 mm; acquisition matrix, 256 × 256; flip angle, 15; averages, 30; slices, 3; slice thickness, 0.3 mm; and acquisition time, 3 m 40 s. After pre-contrast baseline scans, a bolus of DT-MPIO (n = 5) or control IgG-MPIO (n = 5) contrast agent, 30 mg iron/kg body weight, was injected intravenously, while the animal still positioned in the scanner.…”

“…Histology, immunohistochemistry staining and analysis were performed in matching regions of carotid arteries as described [8,10].…”

“…The synthesis and synergistic binding efficacy of DT-MPIO over single-ligand-MPIO have been reported previously [7,8]. Using MR steady-state gradient echo sequence (GRE) developed specifically for molecular imaging of atherosclerosis, this strategy was utilised to (i) identify and characterise vulnerable plaques and (ii) quantitatively track inflammatory status of plaque progression, in the carotid arteries of an apolipoprotein E-deficient (ApoE −/− ) cuff-implanted mouse model [7,8,10].…”