Multimodality Imaging of Aortic Valve Calcification and Function in a Murine Model of Calcific Aortic Valve Disease and Bicuspid Aortic Valve

Calcific aortic valve disease (CAVD) is a prevailing disease with increasing occurrence and no known medical therapy. mice have a high prevalence of bicuspid aortic valve (BAV), spontaneous aortic valve calcification, and aortic stenosis (AS). F-NaF PET/CT can detect the aortic valve calcification process in humans. However, its feasibility in preclinical models of CAVD remains to be determined. Here, we sought to validate F-NaF PET/CT for tracking murine aortic valve calcification and leveraged it to examine the development of calcification with aging and its interdependence with BAV and AS in mice. mice at 3-4 mo, 10-16 mo, and 18-24 mo underwent echocardiography, F-NaF PET/CT ( = 34, or autoradiography ( = 45)), and tissue analysis. A subset of mice underwent both PET/CT and autoradiography ( = 12). The aortic valve signal was quantified as SUV on PET/CT and as percentage injected dose per square centimeter on autoradiography. The valve tissue sections were analyzed by microscopy to identify tricuspid and bicuspid aortic valves. The aortic valve F-NaF signal on PET/CT was significantly higher at 18-24 mo ( < 0.0001) and 10-16 mo ( < 0.05) than at 3-4 mo. Additionally, at 18-24 mo BAV had a higher F-NaF signal than tricuspid aortic valves ( < 0.05). These findings were confirmed by autoradiography, with BAV having significantly higher F-NaF uptake in each age group. A significant correlation between PET and autoradiography data (Pearson = 0.79, < 0.01) established the accuracy of PET quantification. The rate of calcification with aging was significantly faster for BAV ( < 0.05). Transaortic valve flow velocity was significantly higher in animals with BAV at all ages. Finally, there was a significant correlation between transaortic valve flow velocity and aortic valve calcification by both PET/CT ( = 0.55, < 0.001) and autoradiography ( = 0.45, < 0.01). F-NaF PET/CT links valvular calcification to BAV and aging in mice and suggests that AS may promote calcification. In addition to addressing the pathobiology of valvular calcification, F-NaF PET/CT may be a valuable tool for evaluation of emerging therapeutic interventions in CAVD.