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Integrated Backscatter for the In Vivo Quantification of Supraphysiological Vitamin D3-Induced Cardiovascular Calcifications in Rats

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Abstract

Cardiovascular calcifications are frequently found in the aging population and are independent predictors of future cardiovascular events. Integrated backscatter (IB) of ultrasound reflectivity can easily quantify calcifications. For this purpose, 30 male Wistar rats received 25,000 IU/kg/day of vitamin D3 (group 1, n = 8), 18,800 IU/kg/day (group 2, n = 8), or injections with the vehicle only (group 3, n = 14), for 10 weeks. Echocardiographic calibrated IB (cIB) was measured and calculated at baseline and after 10 weeks, followed by ex vivo micro-CT and histopathology of the aortic valve, ascending aorta, and myocardium. After 10 weeks, the mean cIB value of the aortic valve was significantly higher for vitamin D3-dosed animals compared to controls. The mean cIB value of the ascending aorta and the myocardium was also significantly higher in group 1 compared to group 3. In vivo IB results were confirmed by ex vivo micro-CT and histopathology. In conclusion, IB is a non-ionizing, feasible, and reproducible tool to quantify cardiovascular calcifications in an in vivo rat model. The integration of IB in the standard echocardiographic examination for the quantification of cardiovascular calcifications could be useful for serial evaluation of treatment efficacy and for prognosis assessment.

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Abbreviations

A:

Diastolic peak late velocity

AV:

Aortic valve

BSA:

Body surface area

cIB:

Calibrated integrated backscatter

Dec Time:

Deceleration time

E:

Diastolic peak early velocity

FAC:

Fractional area change

IB:

Integrated backscatter

Ind:

Indexed

LA:

Long axis

LV:

Left ventricle

LVAd:

LV cross-sectional area at end diastole

LVAs:

LV cross-sectional area at end systole

LVOT:

Left venticular outflow tract

PG:

Pressure gradient

ROI(s):

Region(s) of interest

ROIM :

ROI myocardium

ROIAscA :

ROI ascending aorta

ROIAVGLOB :

ROI aortic valve, global

ROIAVLA :

ROI aortic valve, long axis

ROIAVSA :

ROI aortic valve, short axis

ROIAVTOT :

ROI aortic valve, total

SA:

Short axis

TVI:

Tissue Velocity Image

VDR:

Vitamin D receptor

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Acknowledgments

This study was supported with a grant from AstraZeneca and Pfizer, Belgium. Bram Roosens has received a scholarship from the OZR, Vrije Universiteit Brussel (2008–2009). Tony Lahoutte is a Senior Clinical Investigator of the Research Foundation—Flanders (Belgium) (FWO). The authors wish to thank Mrs. Cindy Peleman and Mr. Patrick Roncarati for their outstanding technical assistance.

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Authors and Affiliations

  1. Centrum voor Hart- en Vaatziekten (CHVZ), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), 1090, Brussels, Belgium

    Bram Roosens, Steven Droogmans, Gezim Bala, Céline Degaillier, Guy Van Camp & Bernard Cosyns

  2. In Vivo Cellular and Molecular Imaging (ICMI), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), 1090, Brussels, Belgium

    Bram Roosens, Steven Droogmans, Sophie Hernot, Gezim Bala, Vicky Caveliers, Tony Lahoutte, Guy Van Camp & Bernard Cosyns

  3. SkyScan N.V., 2550, Kontich, Belgium

    Jeroen Hostens

  4. Department of Pathology, Centre Hospitalier Universitaire de Liège, 4000, Liège, Belgium

    Joan Somja, Eléonore Delvenne & Philippe Delvenne

  5. Department of Cardiology, UZ Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium

    Bram Roosens

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  1. Bram Roosens
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Correspondence to Bram Roosens.

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Roosens, B., Droogmans, S., Hostens, J. et al. Integrated Backscatter for the In Vivo Quantification of Supraphysiological Vitamin D3-Induced Cardiovascular Calcifications in Rats. Cardiovasc Toxicol 11, 244–252 (2011). https://doi.org/10.1007/s12012-011-9118-y

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  • DOI: https://doi.org/10.1007/s12012-011-9118-y

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