Fluid-Structure Interaction Modeling of the Aortic Hemodynamics in Adult Zebrafish: A Pilot Study Based on Synchrotron X-Ray Tomography

Abstract

The zebrafish is increasingly used as a small animal model for cardiovascular disease, including vascular disorders. Nevertheless, a comprehensive biomechanical understanding of the zebrafish cardiovascular circulation is still lacking and possibilities for phenotyping the zebrafish heart and vasculature at adult -no longer optically transparent -stages are limited. To improve these aspects, we developed imaging-based 3D models of the cardiovascular system of wild-type adult zebrafish. Methods: In vivo high-frequency echocardiography and ex vivo synchrotron x-ray tomography were combined to build fluidstructure interaction finite element models of the fluid dynamics and biomechanics inside the ventral aorta. Results: We successfully generated a reference model of the circulation in adult zebrafish. The dorsal side of the most proximal branching region was found as the location of highest first principal wall stress and was also a location of low wall shear stress. Reynolds number and oscillatory shear were very low compared to mice and humans. Significance: The presented wild-type results provide a first extensive biomechanical reference for adult zebrafish. This framework can be used for advanced cardiovascular phenotyping of adult genetically engineered zebrafish models of cardiovascular disease, showing disruptions of the normal mechano-biology and homeostasis. By providing reference values for key biomechanical stimuli (including wall shear stress and first principal stress) in wild-type animals, and a pipeline for image-based animal-specific computational biomechanical models, this study contributes to a more comprehensive understanding of the role of altered biomechanics and hemodynamics in heritable cardiovascular pathologies.

Early mechanisms of aortic failure in a zebrafish model for thoracic aortic dissection and rupture

“…Ultrasound analysis was performed on zebrafish of 6-7 mpf as previously described 32 . All measurements were performed in Vevo Lab 5.5.0.…”

“…Propagation-based phase-contrast synchrotron X-ray imaging was performed at the TOMCAT (X02DA) beamline of the Swiss Light Source (Paul Scherrer Institute in Villigen, Switzerland) as previously described 46 . Tomographic reconstruction was performed using the Gridrec algorithm after applying the Paganin phase retrieval method 47,48 .…”

“…In a previous study 46 , zebrafish-specific 3D biomechanical fluid-structure interaction models of five different 13-month-old zebrafish were developed. All parameter settings as described in 46 were maintained except for flow through right aortic arch 2, 3 and 4, which was set to nearly zero in order to mimic the vascular organization found in qKO mutants.…”