Molecular MRI is a promising in-vivo modality to detect and quantify morphological and molecular vessel-wall changes in
atherosclerosis. The combination of different molecular
biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-
probe molecular MRI in a mouse-model of progressive
atherosclerosis and in response-to-
therapy. Homozygous
apolipoprotein E knockout mice (ApoE-/-) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-
therapy, a
statin was administered for the same duration. MR imaging was performed before and after administration of an
elastin-specific
gadolinium-based and a macrophage-specific
iron-oxide-based probe. Following in-vivo MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and
laser-inductively-coupled-mass-spectrometry. In
atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the
elastin-specific probe demonstrated the highest accumulation in advanced
atherosclerotic-plaques after four-months of HFD, the
iron-oxide-based probe showed highest accumulation in early
atherosclerotic-plaques after two-months of HFD. In-vivo measurements for the
elastin and
iron-oxide-probe were in good agreement with ex-vivo histopathology (
Elastica-van-Giesson
stain: y = 298.2 + 5.8, R2 = 0.83, p < 0.05; Perls'
Prussian-blue-
stain: y = 834.1 + 0.67, R2 = 0.88, p < 0.05). Contrast-to-noise-ratio (CNR) measurements of the
elastin probe were in good agreement with ICP-MS (y = 0.11x-11.3, R² = 0.73, p < 0.05). Late stage
atherosclerotic-plaques displayed the strongest increase in both CNR and
gadolinium concentration (p < 0.05). The
gadolinium probe did not affect the visualization of the
iron-oxide-probe and vice versa. This study demonstrates the feasibility of simultaneous assessment of plaque-burden and inflammatory activity by dual-
probe molecular MRI of progressive
atherosclerosis. The in-vivo detection and quantification of different MR
biomarkers in a single scan could be useful to improve characterization of atherosclerotic-lesions.