On non-Kolmogorov turbulence in blood flow and its possible role in mechanobiological stimulation.

The study of turbulence in physiologic blood flow is important due to its strong relevance to endothelial mechanobiology and vascular disease. Recently, Saqr et al. (Sci Rep 10, 15,492, 2020) discovered non-Kolmogorov turbulence in physiologic blood flow in vivo, traced its origins to the Navier-Stokes equation and demonstrated some of its properties using chaos and hydrodynamic-stability theories. The present work extends these findings and investigates some inherent characteristics of non-Kolmogorov turbulence in monoharmonic and multiharmonic pulsatile flow under ideal physiologic conditions. The purpose of this work is to propose a conjecture for the origins for picoNewton forces that are known to regulate endothelial cells' functions. The new conjecture relates these forces to physiologic momentum-viscous interactions in the near-wall region of the flow. Here, we used high-resolution large eddy simulation (HRLES) to study pulsatile incompressible flow in a straight pipe of [Formula: see text]. The simulations presented Newtonian and Carreau-Yasuda fluid flows, at [Formula: see text], each represented by one, two and three boundary harmonics. Comparison was established based on maintaining constant time-averaged mass flow rate in all simulations. First, we report the effect of primary harmonics on the global power budget using primitive variables in phase space. Second, we describe the non-Kolmogorov turbulence in frequency domain. Third, we investigate the near-wall coherent structures in time and space domains. Finally, we propose a new conjecture for the role of turbulence in endothelial cells' mechanobiology. The proposed conjecture correlates near-wall turbulence to a force field of picoNewton scale, suggesting possible relevance to endothelial cells mechanobiology.

Numerical study on the energy cascade of pulsatile Newtonian and power-law flow models in an ICA bifurcation.

The complex physics and biology underlying intracranial hemodynamics are yet to be fully revealed. A fully resolved direct numerical simulation (DNS) study has been performed to identify the intrinsic flow dynamics in an idealized carotid bifurcation model. To shed the light on the significance of considering blood shear-thinning properties, the power-law model is compared to the commonly used Newtonian viscosity hypothesis. We scrutinize the kinetic energy cascade (KEC) rates in the Fourier domain and the vortex structure of both fluid models and examine the impact of the power-law viscosity model. The flow intrinsically contains coherent structures which has frequencies corresponding to the boundary frequency, which could be associated with the regulation of endothelial cells. From the proposed comparative study, it is found that KEC rates and the vortex-identification are significantly influenced by the shear-thinning blood properties. Conclusively, from the obtained results, it is found that neglecting the non-Newtonian behavior could lead to underestimation of the hemodynamic parameters at low Reynolds number and overestimation of the hemodynamic parameters by increasing the Reynolds number. In addition, we provide physical insight and discussion onto the hemodynamics associated with endothelial dysfunction which plays significant role in the pathogenesis of intracranial aneurysms.

Physiologic blood flow is turbulent.

Contemporary paradigm of peripheral and intracranial vascular hemodynamics considers physiologic blood flow to be laminar. Transition to turbulence is considered as a driving factor for numerous diseases such as atherosclerosis, stenosis and aneurysm. Recently, turbulent flow patterns were detected in intracranial aneurysm at Reynolds number below 400 both in vitro and in silico. Blood flow is multiharmonic with considerable frequency spectra and its transition to turbulence cannot be characterized by the current transition theory of monoharmonic pulsatile flow. Thus, we decided to explore the origins of such long-standing assumption of physiologic blood flow laminarity. Here, we hypothesize that the inherited dynamics of blood flow in main arteries dictate the existence of turbulence in physiologic conditions. To illustrate our hypothesis, we have used methods and tools from chaos theory, hydrodynamic stability theory and fluid dynamics to explore the existence of turbulence in physiologic blood flow. Our investigation shows that blood flow, both as described by the Navier-Stokes equation and in vivo, exhibits three major characteristics of turbulence. Womersley's exact solution of the Navier-Stokes equation has been used with the flow waveforms from HaeMod database, to offer reproducible evidence for our findings, as well as evidence from Doppler ultrasound measurements from healthy volunteers who are some of the authors. We evidently show that physiologic blood flow is: (1) sensitive to initial conditions, (2) in global hydrodynamic instability and (3) undergoes kinetic energy cascade of non-Kolmogorov type. We propose a novel modification of the theory of vascular hemodynamics that calls for rethinking the hemodynamic-biologic links that govern physiologic and pathologic processes.

Computational fluid dynamics simulations of cerebral aneurysm using Newtonian, power-law and quasi-mechanistic blood viscosity models.

Cerebral aneurysm is a fatal neurovascular disorder. Computational fluid dynamics simulation of aneurysm haemodynamics is one of the most important research tools which provide increasing potential for clinical applications. However, computational fluid dynamics modelling of such delicate neurovascular disorder involves physical complexities that cannot be easily simplified. Recently, it was shown that the Newtonian simplification used to close the shear stress tensor of the Navier-Stokes equation is not sufficient to explore aneurysm haemodynamics. This article explores the differences between the latter simplification, non-Newtonian power-law model and a newly proposed quasi-mechanistic model. The modified Krieger model, which treats blood as a suspension of plasma and particles, was implemented in computational fluid dynamics context here for the first time and is made available to the readers in a C# code in the supplementary material of this article. Two middle-cerebral artery and two anterior-communicating artery aneurysms, all ruptured, were utilized here as case studies. It was shown that the modified Krieger model had higher sensitivity for wall shear stress calculations in comparison with the other two models. The modified Krieger model yielded lower wall shear stress values consistently in comparison with the other two models. Moreover, the modified Krieger model has generally predicted higher pressure in the aneurysm models. Based on published aneurysm rupture studies, it is believed that ruptured aneurysms are usually correlated with lower wall shear stress values than unruptured ones. Therefore, this work concludes that the modified Krieger model is a potential candidate for providing better clinical relevance to aneurysm computational fluid dynamics simulations.

Author Correction: The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study.

Moyamoya disease (MMD) is a rare cerebro-occlusive disease with unknown etiology that can cause both ischemic and hemorrhagic stroke. MMD is characterized by progressive stenosis of the terminal internal carotid artery (ICA) and development of basal brain collaterals. Early-stage MMD is known to cause hemodynamic insufficiency despite mild or moderate stenosis of the intracranial arteries, but the exact mechanism underlying this pathophysiological condition is undetermined. We used high-resolution Large Eddy Simulations to investigate multiple complex hemodynamic phenomena that led to cerebral ischemia in five patients with early-stage MMD. The effects of transitional flow, coherent flow structures and blood shear-thinning properties through regions of tortuous and stenosed arteries were explored and linked to symptomatology. It is evidently shown that in some cases complex vortex structures, such as Rankine-type vortices, redirects blood flow away from some arteries causing significant reduction in blood flow. Moreover, partial blood hammer (PBH) phenomenon was detected in some cases and led to significant hemodynamic insufficiency. PBH events were attributed to the interaction between shear-thinning properties, transitional flow structures and loss of upstream pressure-velocity phase lag. We clearly show that the hemodynamic complexities in early-stage MMD could induce ischemia and explain the non-responsiveness to antiplatelet therapy.

What does computational fluid dynamics tell us about intracranial aneurysms? A meta-analysis and critical review.

Despite the plethora of published studies on intracranial aneurysms (IAs) hemodynamic using computational fluid dynamics (CFD), limited progress has been made towards understanding the complex physics and biology underlying IA pathophysiology. Guided by 1733 published papers, we review and discuss the contemporary IA hemodynamics paradigm established through two decades of IA CFD simulations. We have traced the historical origins of simplified CFD models which impede the progress of comprehending IA pathology. We also delve into the debate concerning the Newtonian fluid assumption used to represent blood flow computationally. We evidently demonstrate that the Newtonian assumption, used in almost 90% of studies, might be insufficient to describe IA hemodynamics. In addition, some fundamental properties of the Navier-Stokes equation are revisited in supplementary material to highlight some widely spread misconceptions regarding wall shear stress (WSS) and its derivatives. Conclusively, our study draws a roadmap for next-generation IA CFD models to help researchers investigate the pathophysiology of IAs.

Evidence for non-Newtonian behavior of intracranial blood flow from Doppler ultrasonography measurements.

Computational fluid dynamics (CFD) studies of intracranial hemodynamics often use Newtonian viscosity model to close the shear rate term in the Navier-Stokes equation. This is based on a commonly accepted hypothesis which state that non-Newtonian effects can be neglected in intracranial blood flow. This study aims to examine the validity of such hypothesis to guide future CFD studies of intracranial hemodynamics. Doppler ultrasonography (DUS) measurements of systolic and diastolic vessel diameter and blood velocity were conducted on 16 subjects (mean age 50.6). The measurements were conducted on the internal carotid (ICA), middle cerebral (MCA), and anterior communicating (AComA) arteries. Systolic and diastolic wall shear stress (WSS) values were calculated via the Hagen-Poiseuille exact solution using Newtonian and three different non-Newtonian models: namely Carreau, power-law and Herschel-Bulkley models. The Weissenberg-Rabinowitsch correction for blood shear-thinning viscosity was applied to the non-Newtonian models. The error percentage between the two sets of models was calculated and discussed. The Newtonian hypothesis was tested statistically and discussed using paired t tests. Significant differences (P < 0.0001) were found between the Newtonian and non-Newtonian WSS in ICA. In MCA and AComA, similar differences were found except in the systole and diastole for the Herschel-Bulkley and power-law models (P = 0.0669, P = 0.7298), respectively. The error between the Newtonian and non-Newtonian models ranged from - 27 to 30% (0.2 to 2.2 Pa). These values could affect the physical interpretation of IA CFD studies. Evidence suggests that the Newtonian assumption may be inappropriate to investigate intracranial hemodynamics. Graphical abstract The WSS estimation error resulting from using the Newtonian assumption compared to three non-Newtonian models for ICA, MCA, and AComA in systole and diastole conditions, based on TCCD measurements of 16 subjects. The error due to the Newtonian assumption ranged from 0.2 to 2.2 Pa (- 27 to 30%). These values could affect the physical interpretation of IA CFD studies.