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

Aortic valve phenotypes in Dcbld2^−/− mice. Shown are examples of aortic valve Masson trichrome (left) and alizarin red (right) staining from Dcbld2^−/− mice with TAV at 3–4 mo, BAV at 3–4 mo, TAV at 18–24 mo, and BAV at 18–24 mo.

¹⁸F-NaF PET/CT of aortic valve calcification in Dcbld2^−/− mice. (A and B) Illustrative coronal images of contrast-enhanced CT, ¹⁸F-NaF PET, and PET/CT from 4-mo-old and 19-mo-old Dcbld2^−/− mice with TAV or BAV. Arrows point to location of aortic valve. (C) Quantification of aortic valve ¹⁸F-NaF signal as SUV_max in different age groups. BAV mice are marked in red. (D and E) Quantification of aortic valve signal as SUV_max in animals with TAV and BAV. (F–H) Quantification of aortic valve signal as SUV_max in mice aged 3–4 mo, 10–16 mo, and 18–24 mo. *P < 0.05. ****P < 0.0001. P values were determined by ANOVA with Tukey multiple comparison post hoc test (C), Kruskal–Wallis with Dunn multiple-comparison post hoc test (D–E), and Mann–Whitney U test (F–H). CE = contrast-enhanced.

Aorta and aortic valve ¹⁸F-NaF autoradiography. (A) Examples of ¹⁸F-NaF autoradiography in animals with TAV or BAV at 3–4 mo, 10–16 mo, and 18–24 mo. Arrows point to aortic valve. (B) Quantification of aortic valve ¹⁸F-NaF uptake across different age groups. BAV mice are marked in red. (C and D) Quantification of aortic valve ¹⁸F-NaF uptake in animals with TAV and BAV. (E–G) Quantification of aortic valve signal in mice aged 3–4 mo, 10–16 mo, and 18–24 mo. *P < 0.05. **P < 0.01. ***P < 0.001. P values were determined by ANOVA with Tukey multiple-comparison post hoc test (B), Kruskal–Wallis with Dunn multiple-comparison post hoc test (C and D), and Mann–Whitney U test (E–G). Scale bar = 0.5 cm.

Correlation between aortic valve ¹⁸F-NaF signal by PET and autoradiography. (A and B) Illustrative coronal contrast-enhanced CT, ¹⁸F-NaF PET, and PET/CT images in 19-mo-old Dcbld2^−/− mice with TAV and BAV (A) and their respective aorta and aortic valve autoradiography (B). Arrows point to location of aortic valve. (C and D) Correlation of aortic valve ¹⁸F-NaF uptake quantified by PET and autoradiography in same animals (C) and average signal per group (D). Linear regression lines are shown, with 95% confidence interval of line of best fit as dotted lines. SE bars for each group are shown in D. *P < 0.05 and **P < 0.01 for Pearson correlations. Scale bar = 0.5 cm.

Aortic valve phenotype and calcification rate in Dcbld2^−/− mice. Relation between ¹⁸F-NaF uptake measured by PET (A) and autoradiography (B), and animal age in mice with TAV and BAV. Linear regression lines are shown, with 95% confidence interval of line of best fit as dotted lines.