Changes in microarchitecture of atherosclerotic calcification assessed by 18F-NaF PET and CT after a progressive exercise regimen in hyperlipidemic mice

Atherosclerosis Imaging with 18F-Sodium Fluoride PET

“…confirmed the prevailing perception that NaF targets microcalcifications that have a greater surface than aggregated calcification [ 10 ]. Regarding the question of which arterial wall compartment first experiences NaF-detectable microcalcifications, the Creager study demonstrated that NaF binds to microcalcifications formed by calcifying extracellular vesicles delivered from vascular smooth muscle cells, and it was shown in animal studies that exercise in hyperlipidemic mice (ApoE −/− ) with baseline aortic calcification is associated with a reduction in aortic NaF uptake, whereas the fold change in aortic calcification measured by CT remained constant [ 28 ]. Moreover, when comparing uremic ApoE −/− mice with non-uremic ApoE −/− mice or control mice, the heart and close-by aorta showed both early and sustained NaF-uptake, which may be associated with endothelial activation in segments with vascular remodeling [ 29 ].…”

“…The extent to which these studies in rodent models translate to humans is not clear. Furthermore, as Hsu et al [ 28 ] noted, it is possible that coronary artery calcification could be modulated very differently by exercise than aortic calcification. Large animal models will be essential for elucidating coronary artery calcification mechanisms in disease [ 30 ].…”

X-ray Micro-Computed Tomography: An Emerging Technology to Analyze Vascular Calcification in Animal Models

“…18 F-sodium fluoride micro-positron emission tomography ( 18 F-NaF µPET) is a sensitive and specific method for detecting calcifications in blood vessels and offers a novel opportunity to discriminate between micro- and macro-calcifications in pre-clinical animal models in vivo [ 7 , 130 , 132 ]. 18 F-sodium fluoride binds to the surface of hydroxyapatite crystals, where the hydroxyl ion is exchanged with the 18 F ion to form fluorapatite.…”

“…18 F-sodium fluoride binds to the surface of hydroxyapatite crystals, where the hydroxyl ion is exchanged with the 18 F ion to form fluorapatite. Importantly, 18 F-NaF has been shown to bind calcifications in murine blood vessels that have not been readily detected by µCT [ 130 , 132 ]. These microcalcifications have a large surface area relative to the amount of calcium, and vascular 18 F-NaF uptake is suggested to be a measure of the total calcification surface area and/or degree of metabolic activity [ 4 , 133 ].…”

“…In contrast, µCT is a measure of calcium mineral content regardless of surface area or metabolic activity. Therefore, combining µCT and 18 F-sodium fluoride µPET could offer a novel opportunity to analyze both micro- and macro-calcifications in pre-clinical models of vascular calcification in vivo ( Figure 7 A–C) [ 130 , 132 ].…”