An Integrated Framework to Quantitatively Link Mouse-Specific Hemodynamics to Aneurysm Formation in Angiotensin II-infused ApoE −/− mice

Abstract

Locally disturbed flow has been suggested to play a (modulating) role in abdominal aortic aneurysm (AAA) formation, but no longitudinal studies have been performed yet due to (a.o.) a lack of human data prior to AAA formation. In this study we made use of recent advances in small animal imaging technology in order to set up entirely mouse-specific computational fluid dynamics (CFD) simulations of the abdominal aorta in an established ApoE -/- mouse model of AAA formation, combining (i) in vivo contrast-enhanced micro-CT scans (geometrical model) and (ii) in vivo high-frequency ultrasound scans (boundary conditions). Resulting areas of disturbed flow at baseline were compared to areas of AAA at end-stage. Qualitative results showed that AAA dimension is maximal in areas that are situated proximal to those areas that experience most disturbed flow in three out of four S developing an AAA. Although further quantitative analysis did not reveal any obvious relationship between areas that experience most disturbed flow and the end-stage AAA dimensions, we cannot exclude that hemodynamics play a role in the initial phases of AAA formation. Due to its mouse-specific and in vivo nature, the presented methodology can be used in future research to link detailed and animal-specific (baseline) hemodynamics to (end-stage) arterial disease in longitudinal studies in mice.

The influence of anesthesia and fluid–structure interaction on simulated shear stress patterns in the carotid bifurcation of mice

“…Many authors have tried to link local disease patterns to focal zones of locally disturbed shear stress using rigid-walled models of either the aortic arch (Assemat et al, 2014;Feintuch et al, 2007;Suo et al, 2007;Yap et al, 2014), the abdominal aorta (Ford et al, 2011;Greve et al, 2006;Trachet et al, 2011b;Willett et al, 2010) or both (Hoi et al, 2011;Huo et al, 2008;Van Doormaal et al, 2014). The findings of publications that focused on regular WSS patterns (Feintuch et al, 2007;Greve et al, 2006;Huo et al, 2008;Suo et al, 2007;Willett et al, 2010;Yap et al, 2014) are not affected much by our results.…”

“…The findings of publications that focused on regular WSS patterns (Feintuch et al, 2007;Greve et al, 2006;Huo et al, 2008;Suo et al, 2007;Willett et al, 2010;Yap et al, 2014) are not affected much by our results. However, some findings of publications that focused on the oscillatory patterns of WSS (Assemat et al, 2014;Ford et al, 2011;Hoi et al, 2011;Trachet et al, 2011b;Van Doormaal et al, 2014) might need to be re-interpreted. In this respect it is important to keep in mind that our results were obtained in the carotid artery, and our conclusions may therefore not be valid in other aspects of the aorta.…”

“…Nevertheless steady state CFD WSS patterns in the common carotid artery have been linked to the uptake of plasma macromolecules (Mohri et al, 2014) or local wall thickness (Cheng et al, 2004). Transient CFD simulations have been used to link TAWSS and OSI patterns to aneurysm progression on a within-subject basis (Ford et al, 2011;Trachet et al, 2011b). In the carotid artery, transient CFD has been used to link wall shear stress patterns with plaque development (Assemat et al, 2014).…”

Inverse modelling of image-based patient-specific blood vessels: zero-pressure geometry andin vivostress incorporation

“…A mouse-specific 3D geometry of the aortic lumen containing four side branches was obtained in vivo, by segmentation of micro-CT (Triumph, Gamma Medica) images in Mimics (Materialise). In order to obtain sufficient contrast during the imaging process the mouse was intravenously injected with Aurovist (Nanoprobes), a contrast agent which provided satisfying results in earlier studies [1]. Using pyFormex [24] a structured grid was projected onto the from segmentation resulting outer surface yielding a hexahedral mesh for the aortic wall, Figure 4a, according to the method of De Santis et al [25].…”

“…Together with pressure measurements there is sufficient data available to include patient-specific boundary conditions in computational fluid dynamics (CFD), computational structural dynamics (CSD) and even fluid-structure interaction (FSI) simulations. In CFD models the flow-related measurements can be imposed directly [1] or incorporated into windkessel and/or 1D models [2] at the inlet and outlets. In CSD models the in vivo data can be used to optimize the constitutive law for the tissue material [3] originally obtained by fitting ex vivo measurements.…”