Vulnerable plaque detection and quantification with gold particle–enhanced computed tomography in atherosclerotic mouse models

Recently, an apolipoprotein E deficient (ApoE-/-) mouse model with a mutation (C1039G+/-) in the fibrillin-1 (Fbn1) gene (ApoE-/-Fbn1C1039G+/- mouse model) has been developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE-/- mouse model where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aims to in-vivo measure and quantify the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold-nanoparticle-enhanced micro computed tomography (μCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the μCT scans, regions of the artery wall with contrast agent present were calculated and visualized in 3D. From this information the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE-/-Fbn1C1039G+/- compared to the ApoE-/- mice. Regional differences between the branches were also observable and quantifiable. In conclusion, we developed and applied a methodology based on gold-particle enhanced μCT to visualize the presence of macrophages in atherosclerotic plaques in-vivo