Accumulation of Atherosclerotic Plaque in Mouse Aortic Valves Determined by MRI
Hanne Hakkarainen1, Jaana Rysä2, Anna-Kaisa Ruotsalainen1, Anna-Liisa Levonen1, and Timo Liimatainen1,3

1A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, 2School of Pharmacy, University of Eastern Finland, Kuopio, Finland, 3Imaging Center, Kuopio University Hospital, Kuopio, Finland

Synopsis

High resolution cine-MRI was applied for examining aortic valve function and atherosclerotic plaque accumulation in the valves in mice on a high fat diet. The end systolic images of the aortic valves of these mice showed clear signs of atherosclerotic fat accumulation and dysfunction of the valves. This implies that the cine-MRI method provides a noninvasive tool for monitoring atherosclerotic plaques in the mouse aortic valves.

Introduction

Aortic valve disease is a condition where the three-leaved valve between heart left ventricle and aorta is not working properly. It may be either not opening fully causing obstruction to blood flow (aortic valve stenosis) or it is not closing properly resulting in a leakage and backward blood flow (aortic valve regurgitation) 1. The non-invasive cardiac MRI has been found potential in imaging aortic valve stenosis and regurgitation, but there is a room for improvement in the image resolution to be able to accurately detect the accumulation of atherosclerotic plaque and calcification in the valve 2,3,4. In this study, high resolution cine-imaging was applied for detecting atherosclerotic plaque accumulation in the aortic valves in hyperlipidemic mice undergoing high fat diet.

Materials and Methods

6 LDLR-/-ApoB100/100 mice were on a high fat diet (42 % of calories from fat) for 5 months. In addition, one C57BL/6 control mouse was included in this study for comparison. The mice were imaged at 7T Bruker Pharmascan using volume transmitter and surface receiver coil. The MRI scans consisted of 6-8 cine-images covering the whole heart from apex to aorta to examine the heart function. Parameters for cine imaging were the following; TR =8 ms, TE = 2 ms, FOV = 4 x 4 cm2, matrix size 192 x 192, 1 slice, slice thickness 1 mm, 10-12 frames depending on heart rate, and 2 averages. The size of the left ventricle was determined from the end diastolic and end systolic images from each slice and combined to obtain the end diastolic and end systolic volumes (EDV and ESV, respectively. From these the ejection fraction (EF) was calculated: EF = 1-EDV/ESV. End systolic aortic valve function was examined by imaging the cross section of the aorta at valve level using cine sequence with slice thickness of 0.6 mm. Other parameters were the following; TR = 8 ms, TE = 2 ms, FOV = 1,5 x 3 cm2, matrix size 192 x 192, 1 slice, and 3 averages. From these images, the area of aortic valve orifice was determined and compared to the total area of aorta.

Results and Discussion

From the cine images, the aorta wall and the accumulated atherosclerotic plaque was clearly separated. The valve function was limited (Figure 1.) suggesting stenosis/regurgitation in the mice with high fat diet. The area of the orifice was 43 ± 5 % (mean ± SEM) of the total area of aorta in these mice. EF of 6 mice was 60 ± 2 % (mean ± SEM) being lower than reported values from normal mice 5.

Conclusion

We were able to clearly visualize the dysfunction of the aortic valves and accumulated atherosclerotic plaque to the mouse aortic valve. The cine-MRI provides a non-invasive tool to monitor aortic atherosclerotic plaques.

Acknowledgements

Academy of Finland (JR), Sigrid Juselius Foundation (TL), and Instrumentarium Science Foundation (HH).

References

1. Otto CM and Prendergast B. Aortic-Valve Stenosis - From Patients at Risk to Severe Valve Obstruction. N Engl J Med 2014;371:744-56, 2. Kupfahl C et al. Evaluation of aortic stenosis by cardiovascular magnetic resonance imaging: comparison with established routine clinical techniques. Heart 2004;90:893–901, 3. Miller JD et al. Lowering Plasma Cholesterol Levels Halts Progression of Aortic Valve Disease in Mice. Circulation 2009;119:2693-2701, 4. Berry CJ et al. Biventricular adaptation to volume overload in mice with aortic regurgitation. Journal of Cardiovascular Magnetic Resonance 2009;11:27, 5. Schneider JE et al. Long-term stability of cardiac function in normal and chronically failing mouse hearts in a vertical-bore MR system. MAGMA 2004;17:162–169.

Figures

Figure 1. Representative examples of aortic valves at systole from one control mouse (left) and two mice with high fat diet (center and right). The atherosclerotic plaque is highlighted with red and the blue line outlines the aorta wall.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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