Contrast-enhanced micro-CT imaging in murine carotid arteries: a new protocol for computing wall shear stress.
BACKGROUND
Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atherosclerotic mouse model. To determine WSS in vivo, detailed 3D geometry of the vessel network is required. However, a protocol to reconstruct 3D murine vasculature using this animal model is lacking. In this project, we evaluated the adequacy of eXIA 160, a small animal contrast agent, for assessing murine vascular network on micro-CT. Also, a protocol was established for vessel geometry segmentation and WSS analysis.


METHODS
A tapering cast was placed around the right common carotid artery (RCCA) of ApoE-/-mice (n = 8). Contrast-enhanced micro-CT was performed using eXIA 160. An innovative local threshold-based segmentation procedure was implemented to reconstruct 3D geometry of the RCCA. The reconstructed RCCA was compared to the vessel geometry using a global threshold-based segmentation method. Computational fluid dynamics was applied to compute the velocity field and WSS distribution along the RCCA.


RESULTS
eXIA 160-enhanced micro-CT allowed clear visualization and assessment of the RCCA in all eight animals. No adverse biological effects were observed from the use of eXIA 160. Segmentation using local threshold values generated more accurate RCCA geometry than the global threshold-based approach. Mouse-specific velocity data and the RCCA geometry generated 3D WSS maps with high resolution, enabling quantitative analysis of WSS. In all animals, we observed low WSS upstream of the cast. Downstream of the cast, asymmetric WSS patterns were revealed with variation in size and location between animals.


CONCLUSIONS
eXIA 160 provided good contrast to reconstruct 3D vessel geometry and determine WSS patterns in the RCCA of the atherosclerotic mouse model. We established a novel local threshold-based segmentation protocol for RCCA reconstruction and WSS computation. The observed differences between animals indicate the necessity to use mouse-specific data for WSS analysis. For our future work, our protocol makes it possible to study in vivo WSS longitudinally over a growing plaque.
Department of Biomedical Engineering, Thorax Center, Erasmus MC, Wytemaweg 80, Ee2338, 3015CN, Rotterdam, The Netherlands.
Ruoyu
R
Xing
IBiTech-bioMMeda, iMinds Medical IT, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium.
David
D
De Wilde
Department of Biomedical Engineering, Thorax Center, Erasmus MC, Wytemaweg 80, Ee2338, 3015CN, Rotterdam, The Netherlands.
Gayle
G
McCann
Department of Genetics, Erasmus MC, Wytemaweg 80, Ee720, 3015CN, Rotterdam, The Netherlands.
Yanto
Y
Ridwan
Department of Biomedical Engineering, Thorax Center, Erasmus MC, Wytemaweg 80, Ee2338, 3015CN, Rotterdam, The Netherlands.
Jelle T C
JT
Schrauwen
Department of Biomedical Engineering, Thorax Center, Erasmus MC, Wytemaweg 80, Ee2338, 3015CN, Rotterdam, The Netherlands.
Anton F W
AF
van der Steen
Department of Biomedical Engineering, Thorax Center, Erasmus MC, Wytemaweg 80, Ee2338, 3015CN, Rotterdam, The Netherlands. f.gijsen@erasmusmc.nl.
Frank J H
FJ
Gijsen
Department of Biomedical Engineering, Thorax Center, Erasmus MC, Wytemaweg 80, Ee2338, 3015CN, Rotterdam, The Netherlands.
Kim
K
Van der Heiden
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001783:Blood Flow Velocity; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003287:Contrast Media / Q000737:chemistry*; D003331:Coronary Vessels / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D033081:Shear Strength; D013314:Stress, Mechanical; D055114:X-Ray Microtomography / Q000379:methods*
D001057:Apolipoproteins E; D003287:Contrast Media
Atherosclerosis; Contrast media; Image segmentation; Micro-CT imaging; Wall shear stress