PT  - JOURNAL ARTICLE
AU  - Ahmad, Azmi A.
AU  - Ghim, Mean
AU  - Toczek, Jakub
AU  - Neishabouri, Afarin
AU  - Ojha, Devi
AU  - Zhang, Zhengxing
AU  - Gona, Kiran
AU  - Raza, Muhammad Zawwad
AU  - Jung, Jae-Joon
AU  - Kukreja, Gunjan
AU  - Zhang, Jiasheng
AU  - Guerrera, Nicole
AU  - Liu, Chi
AU  - Sadeghi, Mehran M.
TI  - Multimodality Imaging of Aortic Valve Calcification and Function in a Murine Model of Calcific Aortic Valve Disease and Bicuspid Aortic Valve
AID  - 10.2967/jnumed.123.265516
DP  - 2023 Sep 01
TA  - Journal of Nuclear Medicine
PG  - 1487--1494
VI  - 64
IP  - 9
4099  - http://jnm.snmjournals.org/content/64/9/1487.short
4100  - http://jnm.snmjournals.org/content/64/9/1487.full
SO  - J Nucl Med2023 Sep 01; 64
AB  - Calcific aortic valve disease (CAVD) is a prevailing disease with increasing occurrence and no known medical therapy. Dcbld2−/− mice have a high prevalence of bicuspid aortic valve (BAV), spontaneous aortic valve calcification, and aortic stenosis (AS). 18F-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 18F-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 Dcbld2−/− mice. Methods: Dcbld2−/− mice at 3–4 mo, 10–16 mo, and 18–24 mo underwent echocardiography, 18F-NaF PET/CT (n = 34, or autoradiography (n = 45)), and tissue analysis. A subset of mice underwent both PET/CT and autoradiography (n = 12). The aortic valve signal was quantified as SUVmax 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. Results: The aortic valve 18F-NaF signal on PET/CT was significantly higher at 18–24 mo (P < 0.0001) and 10–16 mo (P < 0.05) than at 3–4 mo. Additionally, at 18–24 mo BAV had a higher 18F-NaF signal than tricuspid aortic valves (P < 0.05). These findings were confirmed by autoradiography, with BAV having significantly higher 18F-NaF uptake in each age group. A significant correlation between PET and autoradiography data (Pearson r = 0.79, P < 0.01) established the accuracy of PET quantification. The rate of calcification with aging was significantly faster for BAV (P < 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 (r = 0.55, P < 0.001) and autoradiography (r = 0.45, P < 0.01). Conclusion: 18F-NaF PET/CT links valvular calcification to BAV and aging in Dcbld2−/− mice and suggests that AS may promote calcification. In addition to addressing the pathobiology of valvular calcification, 18F-NaF PET/CT may be a valuable tool for evaluation of emerging therapeutic interventions in CAVD.