The Impact of Simplified Boundary Conditions and Aortic Arch Inclusion on CFD Simulations in the Mouse Aorta: A Comparison With Mouse-specific Reference Data

Abstract

Computational fluid dynamics (CFD) simulations allow for calculation of a detailed flow field in the mouse aorta and can thus be used to investigate a potential link between local hemodynamics and disease development. To perform these simulations in a murine setting, one often needs to make assumptions (e.g. when mouse-specific boundary conditions are not available), but many of these assumptions have not been validated due to a lack of reference data. In this study, we present such a reference data set by combining high-frequency ultrasound and contrast-enhanced micro-CT to measure (in vivo) the time-dependent volumetric flow waveforms in the complete aorta (including seven major side branches) of 10 male ApoE -/- deficient mice on a C57Bl/6 background. In order to assess the influence of some assumptions that are commonly applied in literature, four different CFD simulations were set up for each animal: (i) imposing the measured volumetric flow waveforms, (ii) imposing the average flow fractions over all 10 animals, presented as a reference data set, (iii) imposing flow fractions calculated by Murray's law, and (iv) restricting the geometrical model to the abdominal aorta (imposing measured flows). We found that - even if there is sometimes significant variation in the flow fractions going to a particular branch - the influence of using average flow fractions on the CFD simulations is limited and often restricted to the side branches. On the other hand, Murray's law underestimates the fraction going to the brachiocephalic trunk and strongly overestimates the fraction going to the distal aorta, influencing the outcome of the CFD results significantly. Changing the exponential factor in Murray's law equation from 3 to 2 (as suggested by several authors in literature) yields results that correspond much better to those obtained imposing the average flow fractions. Restricting the geometrical model to the abdominal aorta did not influence the outcome of the CFD simulations. In conclusion, the presented reference dataset can be used to impose boundary conditions in the mouse aorta in future studies, keeping in mind that they represent a subsample of the total population, i.e., relatively old, non-diseased, male C57Bl/6 ApoE -/- mice.

A 1D model of the arterial circulation in mice

“…Terminal resistances were calculated based on flow rates into major branches that were reported by Trachet et al (2011). At locations where no experimental data were available, we completed the values assuming that the mean wall shear stress (given by Poiseuille's law) was the same as for nearby arteries.…”

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

“…Most of these publications focused on the methodology and the feasibility to calculate WSS in mice and did not link the found patterns (quantitatively or qualitatively) to biological responses or processes (Feintuch et al, 2007;Greve et al, 2006;Huo et al, 2008;Trachet et al, 2011a;Trachet et al, 2009;Van Doormaal et al, 2014). 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).…”

A multi-angle plane wave imaging approach for high frequency 2D flow visualization in small animals: Simulation study in the murine arterial system

“…Multiphysics simulations in the murine aorta 1) 3D-reconstruction murine aorta: A mouse-specific aorta was 3D reconstructed from a set of micro CT-scans (left panel of fig.1), obtained in an in-house bred male mouse (49 days old), demonstrating an abdominal aortic aneurysm (AAA), induced after 28 days of angiotensin II uptake via an implanted osmotic pump [8]. Based on the reconstructed images, the aorta was semi-automatically segmented to select the contrastenhanced lumen using Mimics (Materialise, Leuven, Belgium).…”