Azmi A Ahmad, Mean Ghim, Jakub Toczek, Afarin Neishabouri, Devi Ojha, Zhengxing Zhang, Kiran Gona, Muhammad Zawwad Raza, Jae-Joon Jung, Gunjan Kukreja, Jiasheng Zhang, Nicole Guerrera, Chi Liu, Mehran M Sadeghi
{"title":"Multimodality Imaging of Aortic Valve Calcification and Function in a Murine Model of Calcific Aortic Valve Disease and Bicuspid Aortic Valve.","authors":"Azmi A Ahmad, Mean Ghim, Jakub Toczek, Afarin Neishabouri, Devi Ojha, Zhengxing Zhang, Kiran Gona, Muhammad Zawwad Raza, Jae-Joon Jung, Gunjan Kukreja, Jiasheng Zhang, Nicole Guerrera, Chi Liu, Mehran M Sadeghi","doi":"10.2967/jnumed.123.265516","DOIUrl":null,"url":null,"abstract":"<p><p>Calcific aortic valve disease (CAVD) is a prevailing disease with increasing occurrence and no known medical therapy. <i>Dcbld2<sup>-/-</sup></i> mice have a high prevalence of bicuspid aortic valve (BAV), spontaneous aortic valve calcification, and aortic stenosis (AS). <sup>18</sup>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 <sup>18</sup>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 <i>Dcbld2<sup>-/-</sup></i> mice. <b>Methods:</b> <i>Dcbld2<sup>-/-</sup></i> mice at 3-4 mo, 10-16 mo, and 18-24 mo underwent echocardiography, <sup>18</sup>F-NaF PET/CT (<i>n</i> = 34, or autoradiography (<i>n</i> = 45)), and tissue analysis. A subset of mice underwent both PET/CT and autoradiography (<i>n</i> = 12). The aortic valve signal was quantified as SUV<sub>max</sub> 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. <b>Results:</b> The aortic valve <sup>18</sup>F-NaF signal on PET/CT was significantly higher at 18-24 mo (<i>P</i> < 0.0001) and 10-16 mo (<i>P</i> < 0.05) than at 3-4 mo. Additionally, at 18-24 mo BAV had a higher <sup>18</sup>F-NaF signal than tricuspid aortic valves (<i>P</i> < 0.05). These findings were confirmed by autoradiography, with BAV having significantly higher <sup>18</sup>F-NaF uptake in each age group. A significant correlation between PET and autoradiography data (Pearson <i>r</i> = 0.79, <i>P</i> < 0.01) established the accuracy of PET quantification. The rate of calcification with aging was significantly faster for BAV (<i>P</i> < 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 (<i>r</i> = 0.55, <i>P</i> < 0.001) and autoradiography (<i>r</i> = 0.45, <i>P</i> < 0.01). <b>Conclusion:</b> <sup>18</sup>F-NaF PET/CT links valvular calcification to BAV and aging in <i>Dcbld2<sup>-/-</sup></i> mice and suggests that AS may promote calcification. In addition to addressing the pathobiology of valvular calcification, <sup>18</sup>F-NaF PET/CT may be a valuable tool for evaluation of emerging therapeutic interventions in CAVD.</p>","PeriodicalId":16758,"journal":{"name":"Journal of Nuclear Medicine","volume":"64 9","pages":"1487-1494"},"PeriodicalIF":9.1000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478817/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nuclear Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2967/jnumed.123.265516","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/15 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
The Journal of Nuclear Medicine (JNM), self-published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), provides readers worldwide with clinical and basic science investigations, continuing education articles, reviews, employment opportunities, and updates on practice and research. In the 2022 Journal Citation Reports (released in June 2023), JNM ranked sixth in impact among 203 medical journals worldwide in the radiology, nuclear medicine, and medical imaging category.