Computational hemodynamic optimization predicts dominant aortic arch selection is driven by embryonic outflow tract orientation in the chick embryo

Kowalski, William J.; Teslovich, Nikola C.; Dur, Onur; Keller, Bradley B.; Pekkan, Kerem

doi:10.1007/s10237-012-0373-z

Cited by 20 publications

(24 citation statements)

References 96 publications

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“…The percentage of total volumetric flow coming out of each outlet boundary was determined according to Murray’s law [29], which states that flow in vessels tend to scale according to the 3 rd power of vessel radius. Murray’s law is widely used in CFD studies in the literature [30]–[32] and provide physiological estimates. With the volumetric flow rate at the descending aorta outlet, we could thus calculate volumetric flow rate at other outlets, and by assuming parabolic profiles, we could compute flow velocities at these outlets.…”

Section: Methodsmentioning

confidence: 99%

Characterizaton of the Vessel Geometry, Flow Mechanics and Wall Shear Stress in the Great Arteries of Wildtype Prenatal Mouse

2014

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IntroductionAbnormal fluid mechanical environment in the pre-natal cardiovascular system is hypothesized to play a significant role in causing structural heart malformations. It is thus important to improve our understanding of the prenatal cardiovascular fluid mechanical environment at multiple developmental time-points and vascular morphologies. We present such a study on fetal great arteries on the wildtype mouse from embryonic day 14.5 (E14.5) to near-term (E18.5).MethodsUltrasound bio-microscopy (UBM) was used to measure blood velocity of the great arteries. Subsequently, specimens were cryo-embedded and sectioned using episcopic fluorescent image capture (EFIC) to obtain high-resolution 2D serial image stacks, which were used for 3D reconstructions and quantitative measurement of great artery and aortic arch dimensions. EFIC and UBM data were input into subject-specific computational fluid dynamics (CFD) for modeling hemodynamics.ResultsIn normal mouse fetuses between E14.5–18.5, ultrasound imaging showed gradual but statistically significant increase in blood velocity in the aorta, pulmonary trunk (with the ductus arteriosus), and descending aorta. Measurement by EFIC imaging displayed a similar increase in cross sectional area of these vessels. However, CFD modeling showed great artery average wall shear stress and wall shear rate remain relatively constant with age and with vessel size, indicating that hemodynamic shear had a relative constancy over gestational period considered here.ConclusionOur EFIC-UBM-CFD method allowed reasonably detailed characterization of fetal mouse vascular geometry and fluid mechanics. Our results suggest that a homeostatic mechanism for restoring vascular wall shear magnitudes may exist during normal embryonic development. We speculate that this mechanism regulates the growth of the great vessels.

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Section: Methodsmentioning

confidence: 99%

Characterizaton of the Vessel Geometry, Flow Mechanics and Wall Shear Stress in the Great Arteries of Wildtype Prenatal Mouse

2014

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“…Computational studies have been performed to investigate the influence of hemodynamics on developmental phenomena such as atrioventricular valve formation, aortic arch development and cardiac looping, e.g. (Taber et al 1993; Groenendijk et al 2005; Pekkan et al 2008; Wang et al 2009; Taber 2009; Yalcin et al 2011; Freund et al 2012; Kowalski et al 2012; Kowalski et al 2014; Biechler et al 2014). Groups have also investigated hemodynamics in the chick embryonic OFT (Bharadwaj et al 2012; Menon et al 2015).…”

Section: Introductionmentioning

confidence: 99%

4D subject-specific inverse modeling of the chick embryonic heart outflow tract hemodynamics

Goenezen

Chivukula

Midgett

et al. 2015

Biomech Model Mechanobiol

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Blood flow plays a critical role in regulating embryonic cardiac growth and development, with altered flow leading to congenital heart disease. Progress in the field, however, is hindered by a lack of quantification of hemodynamic conditions in the developing heart. In this study, we present a methodology to quantify blood flow dynamics in the embryonic heart using subject-specific computational fluid dynamics (CFD) models. While the methodology is general, we focused on a model of the chick embryonic heart outflow tract (OFT), which distally connects the heart to the arterial system, and is the region of origin of many congenital cardiac defects. Using structural and Doppler velocity data collected from optical coherence tomography (OCT), we generated 4D (3D + time) embryo-specific CFD models of the heart OFT. To replicate the blood flow dynamics over time during the cardiac cycle, we developed an iterative inverse-method optimization algorithm, which determines the CFD model boundary conditions such that differences between computed velocities and measured velocities at one point within the OFT lumen are minimized. Results from our developed CFD model agree with previously measured hemodynamics in the OFT. Further, computed velocities and measured velocities differ by less than 15% at locations that were not used in the optimization, validating the model. The presented methodology can be used in quantifications of embryonic cardiac hemodynamics under normal and altered blood flow conditions, enabling an in depth quantitative study of how blood flow influences cardiac development.

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“…When the growth model was applied to a simplified cylindrical model of the developing heart ventricle, volumetric (mass) growth of the developing ventricle from HH21 to HH29 was reproduced. Kowalski et al (2012) provide a new model to predict aortic arch formation based on the outflow tract orientation and the associated alterations in hemodynamics. An extensive review of embryonic growth models is provided therein as well.…”

Section: Modeling Heart Developmentmentioning

confidence: 99%

Biomechanics of early cardiac development

Goenezen

Rennie

Rugonyi

2012

Biomech Model Mechanobiol

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Biomechanics affect early cardiac development, from looping to the development of chambers and valves. Hemodynamic forces are essential for proper cardiac development, and their disruption leads to congenital heart defects. A wealth of information already exists on early cardiac adaptations to hemodynamic loading, and new technologies, including high resolution imaging modalities and computational modeling, are enabling a more thorough understanding of relationships between hemodynamics and cardiac development. Imaging and modeling approaches, used in combination with biological data on cell behavior and adaptation, are paving the road for new discoveries on links between biomechanics and biology and their effect on cardiac development and fetal programming.

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Computational hemodynamic optimization predicts dominant aortic arch selection is driven by embryonic outflow tract orientation in the chick embryo

Cited by 20 publications

References 96 publications

Characterizaton of the Vessel Geometry, Flow Mechanics and Wall Shear Stress in the Great Arteries of Wildtype Prenatal Mouse

Characterizaton of the Vessel Geometry, Flow Mechanics and Wall Shear Stress in the Great Arteries of Wildtype Prenatal Mouse

4D subject-specific inverse modeling of the chick embryonic heart outflow tract hemodynamics

Biomechanics of early cardiac development

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