Development of Ultrasound Phantom Made of Transparent Material: Feasibility of Optical Particle Image Velocimetry.

OBJECTIVE: The need for ultrasound flow phantoms to validate ultrasound systems requires the development of materials that can clearly visualize the flow inside for measurement purposes. METHODS: A transparent ultrasound flow phantom material composed of poly(vinyl alcohol) hydrogel (PVA-H) with dimethyl sulfoxide (DMSO) and water solution manufactured using the freezing method and mixed with quartz glass powder to exhibit scattering effects is proposed. To achieve transparency of the hydrogel phantom, the refractive index (RI) was changed to match that of the glass by modifying the PVA concentration and the ratio of DMSO to water in the solvent. The feasibility of optical particle image velocimetry (PIV) was verified by comparing an acrylic rectangular cross-section channel with a rigid wall. After the feasibility tests, an ultrasound flow phantom was fabricated to conduct ultrasound B-mode visualization and Doppler-PIV comparison. DISCUSSION: The results revealed that the PIV measured through PVA-H material exhibited 0.8% error in the measured maximum velocity compared with PIV through the acrylic material. B-mode images are similar to real tissue visualization with a limitation of a higher sound velocity, when compared with human tissue, of 1792 m/s. Doppler measurement of the phantom revealed approximately 120% and 19% overestimation of maximum and mean velocities, respectively, compared with those from PIV. CONCLUSION: The proposed material possesses the advantage of the single-phantom ability to improve the ultrasound flow phantom for validation of flow.

A Parametric Study of Flushing Conditions for Improvement of Angioscopy Visibility.

During an angioscopy operation, a transparent liquid called dextran is sprayed out from a catheter to flush the blood away from the space between the camera and target. Medical doctors usually inject dextran at a constant flow rate. However, they often cannot obtain clear angioscopy visibility because the flushing out of the blood is insufficient. Good flushing conditions producing clear angioscopy visibility will increase the rate of success of angioscopy operations. This study aimed to determine a way to improve the clarity for angioscopy under different values for the parameters of the injection waveform, endoscope position, and catheter angle. We also determined the effect of a stepwise waveform for injecting the dextran only during systole while synchronizing the waveform to the cardiac cycle. To evaluate the visibility of the blood-vessel walls, we performed a computational fluid dynamics (CFD) simulation and calculated the visible area ratio (VAR), representing the ratio of the visible wall area to the total area of the wall at each point in time. Additionally, the normalized integration of the VAR called the area ratio (ARVAR) represents the ratio of the visible wall area as a function of the dextran injection period. The results demonstrate that the ARVAR with a stepped waveform, bottom endoscope, and three-degree-angle catheter results in the highest visibility, around 25 times larger than that under the control conditions: a constant waveform, a center endoscope, and 0 degrees. This set of conditions can improve angioscopy visibility.

Flush Flow Behaviour Affected by the Morphology of Intravascular Endoscope: A Numerical Simulation and Experimental Study.

Background: Whilst intravascular endoscopy can be used to identify lesions and assess the deployment of endovascular devices, it requires temporary blockage of the local blood flow during observation, posing a serious risk of ischaemia. Objective: To aid the design of a novel flow-blockage-free intravascular endoscope, we explored changes in the haemodynamic behaviour of the flush flow with respect to the flow injection speed and the system design. Methods: We first constructed the computational models for three candidate endoscope designs (i.e., Model A, B, and C). Using each of the three endoscopes, flow patterns in the target vessels (straight, bent, and twisted) under three different sets of boundary conditions (i.e., injection speed of the flush flow and the background blood flowrate) were then resolved through use of computational fluid dynamics and in vitro flow experiments. The design of endoscope and its optimal operating condition were evaluated in terms of the volume fraction within the vascular segment of interest, as well as the percentage of high-volume-fraction area (PHVFA) corresponding to three cross-sectional planes distal to the microcatheter tip. Results: With a mild narrowing at the endoscope neck, Model B exhibited the highest PHVFA, irrespective of location of the cross-sectional plane, compared with Models A and C which, respectively, had no narrowing and a moderate narrowing. The greatest difference in the PHVFA between the three models was observed on the cross-sectional plane 2 mm distal to the tip of the microcatheter (Model B: 33% vs. Model A: 18%). The background blood flowrate was found to have a strong impact on the resulting volume fraction of the flush flow close to the vascular wall, with the greatest difference being 44% (Model A). Conclusion: We found that the haemodynamic performance of endoscope Model B outperformed that of Models A and C, as it generated a flush flow that occupied the largest volume within the vascular segment of interest, suggesting that the endoscope design with a diameter narrowing of 30% at the endoscope neck might yield images of a better quality.

Association Between Aneurysmal Haemodynamics and Device Microstructural Characteristics After Flow-Diversion Treatments With Dual Stents of Different Sizes: A Numerical Study.

OBJECTIVES: Treating intracranial aneurysms with flow-diverting stents sometimes requires deployment of a second device. Herein we quantify the sizing effects of devices in dual-stent treatments upon the final stent microstructure and the post-treatment aneurysmal haemodynamics. METHODS: Fifteen sidewall ICA aneurysm geometries were included. Using a virtual stenting technique, we implanted either one or two stents for each aneurysm treatment considered, with each stent specified as one of two different sizes, yielding a total of two single-stent and fouir dual-stent treatment scenarios for each aneurysm. Three stent microstructural parameters and nine aneurysmal haemodynamic parameters were quantified and systematically compared across the 90 treatment scenarios. RESULTS: Deployment of a second stent further reduced the aneurysmal inflow rate (IR) and energy loss (EL) by, respectively, 14 ± 11% (p = 0.001) and 9 ± 12% (p = 0.056), relative to the untreated condition. Sizing effects of the earlier-deployed stent led to largest differences of 6.9% for the final IR reduction and 11.1% for the EL, whereas sizing effects from the later-deployed stent were minor (≤2.1%). The change in stent pore size was the only microstructural parameter demonstrating a strong correlation with the reduction in the post-treatment aneurysmal haemodynamics, in terms of the IR (r = 0.50, p < 0.001) and pressure drop (r = 0.63, p < 0.001). CONCLUSION: Size of the earlier-deployed stent has substantial effects on the final haemodynamic outcomes after dual-stent treatment. The average pore size of stent wires at the aneurysm orifice shows promise as a potential index for predicting the efficacy of flow-diversion treatments.

Incomplete stent expansion in flow-diversion treatment affects aneurysmal haemodynamics: a quantitative comparison of treatments affected by different severities of malapposition occurring in different segments of the parent artery.

Incomplete stent expansion (IncSE) is occasionally seen in flow-diversion (FD) treatment of intracranial aneurysms; however, its haemodynamic consequences remain inconclusive. Through a parametric study, we quantify the aneurysmal haemodynamics subject to different severities of IncSE occurring in different portions of the stent. Two patient cases with IncSE confirmed in vivo were studied. To investigate a wider variety of IncSE scenarios, we modelled IncSE at two severity levels respectively located in the proximal, central, or distal segment of a stent, yielding a total of 14 treatment scenarios (including the ideal deployment). We examined stent wire configurations in 14 scenarios and resolved aneurysm haemodynamics through computational fluid dynamics (CFD). A considerable degradation of aneurysm flow-reduction performance was observed when central or distal IncSE occurred, with the maximal elevations of the inflow rate (IR) and energy loss (EL) being 10% and 15%. The underlying mechanism might be the increased resistance for flow to remain within the FD stent, which forces more blood to leak into the aneurysm sac. Counter-intuitively, a slight reduction of aneurysm inflow was associated with proximal IncSE, with the maximal further reduction of the IR and EL being 5% and 8%. This may be due to the disruption of the predominant parent-artery flow by the collapsed wires, which decreased the strength and altered the direction of aneurysmal inflow. The effects of IncSE vary greatly with the location of occurrence, revealing the importance of performing individualised, patient-specific risk assessment before treatment.

Experimental Analysis of Pressure and Flow Alterations During and After Insertion of a Multilayer Flow Modulator into an AAA Model with Incorporated Branch.

PURPOSE: The multilayer flow modulator (MFM) device has been used for the treatment of abdominal aortic aneurysm (AAA) for over a decade. Although several clinical studies have been published, criticism and concern over the device efficacy remain, as no quantitative analysis that describes its mechanism has been performed yet. The aim of this study was to experimentally evaluate the effect of MFM device deployment on aneurysmal pressure and branch perfusion. MATERIALS AND METHODS: An experimental flow and pressure monitoring system was developed to analyze the MFM deployment procedure performed by a qualified radiologist in AAA geometries with and without side branch. Particle image velocimetry experiments were then conducted on models with and without MFM device to evaluate and compare flow patterns and local flow velocity and vorticity in the aneurysm. RESULTS: The experiments revealed no significant change in pressure and flow rate during and after deployment of the MFM device. The flow rate of the incorporated branch was fully preserved. On both models, the aneurysmal flow velocity was significantly reduced. In addition, the device modified local flow patterns, reducing vorticity and better feeding the incorporated branch. CONCLUSION: This experimental study provides the basis for a better understanding of the mechanism of the MFM device, which allows intra-aneurysmal flow to decrease while preserving incorporated branch flow and reducing the risk of type II endoleak. The experimental system developed for this study was effective in simulating an endovascular procedure and studying the safety and effectiveness of endovascular devices.

Prediction of 3D Cardiovascular hemodynamics before and after coronary artery bypass surgery via deep learning.

The clinical treatment planning of coronary heart disease requires hemodynamic parameters to provide proper guidance. Computational fluid dynamics (CFD) is gradually used in the simulation of cardiovascular hemodynamics. However, for the patient-specific model, the complex operation and high computational cost of CFD hinder its clinical application. To deal with these problems, we develop cardiovascular hemodynamic point datasets and a dual sampling channel deep learning network, which can analyze and reproduce the relationship between the cardiovascular geometry and internal hemodynamics. The statistical analysis shows that the hemodynamic prediction results of deep learning are in agreement with the conventional CFD method, but the calculation time is reduced 600-fold. In terms of over 2 million nodes, prediction accuracy of around 90%, computational efficiency to predict cardiovascular hemodynamics within 1 second, and universality for evaluating complex arterial system, our deep learning method can meet the needs of most situations.

Implementation of computer simulation to assess flow diversion treatment outcomes: systematic review and meta-analysis.

INTRODUCTION: Despite a decade of research into virtual stent deployment and the post-stenting aneurysmal hemodynamics, the hemodynamic factors which correlate with successful treatment remain inconclusive. We aimed to examine the differences in various post-treatment hemodynamic parameters between successfully and unsuccessfully treated cases, and to quantify the additional flow diversion achievable through stent compaction or insertion of a second stent. METHODS: A systematic review and meta-analysis were performed on eligible studies published from 2000 to 2019. We first classified cases according to treatment success (aneurysm occlusion) and then calculated the pooled standardized mean differences (SMD) of each available parameter to examine their association with clinical outcomes. Any additional flow diversion arising from the two common strategies for improving the stent wire density was quantified by pooling the results of such studies. RESULTS: We found that differences in the aneurysmal inflow rate (SMD -6.05, 95% CI -10.87 to -1.23, p=0.01) and energy loss (SMD -5.28, 95% CI -7.09 to -3.46, p<0.001) between the successfully and unsuccessfully treated groups were indicative of statistical significance, in contrast to wall shear stress (p=0.37), intra-aneurysmal average velocity (p=0.09), vortex core-line length (p=0.46), and shear rate (p=0.09). Compacting a single stent could achieve additional flow diversion comparable to that by dual-stent implantation. CONCLUSIONS: Inflow rate and energy loss have shown promise as identifiers to discriminate between successful and unsuccessful treatment, pending future research into their diagnostic performance to establish optimal cut-off values.

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.

Assessing Porous Media Permeability in Non-Darcy Flow: A Re-Evaluation Based on the Forchheimer Equation.

In a recent paper published in Materials (Castro et al., 2019), the permeability evaluation of triple periodic minimum surface samples was carried out experimentally. Darcy's law was used under unsuitable conditions, resulting in an underestimation of the results. In this comment, we highlight the problem and propose a new estimation of the permeability using the Forchheimer equation, which is better suited to the experimental conditions.

Development of a stereo dip-coating system for fabrication of tube-shaped blood vessel models.

Tube-shaped blood vessel models that mimic their geometries and mechanical properties can deliver reliable and realistic behavioral information such as deformation and rupture during procedures such as insertion of medical devices. Thickness of vessel walls is an important parameter for fabricating the blood vessel models owing to their strong influence on the model behavior, especially during deformation. The dip-coating method is used to fabricate blood vessel models; however, non-uniform wall thicknesses are observed using this method. This study aimed at finding the characteristics of stereo "angular control dip-coating" (ACDC) system to develop a dip-coating system that can produce tubular models with uniformed wall thickness. The system developed here enables an observation of the substrate behavior from two different views. The conditions of dip-coating used in this study produce 1.36-1.82 mm in the maximum and 0.188-0.435 mm in minimum wall thickness and the fabricated walls cover the realistic range of carotid arterial dimensions. The characteristics of the ACDC system indicate that ACDC is effective for fabricating the uniform wall thickness particularly in the strong curved parts.

Epigenetic response of endothelial cells to different wall shear stress magnitudes: A report of new mechano-miRNAs.

Endothelial cells (ECs) respond to flow stress via a variety of mechanisms, leading to various intracellular responses that can modulate the vessel wall and lead to diseases if the flow is disturbed. Mechano-microRNAs (miRNAs) are a subset of miRNAs in the ECs that are flow responsive. Mechano-miRNAs were shown to be related to atherosclerosis pathophysiology, and a number of them were identified as pathologic. Here, we exposed human carotid ECs to different wall shear stresses (WSS), high and low, and evaluated the response of miRNAs by microarray and quantitative polymerase chain reaction analysis. We discovered five new mechano-miRNAs that were not reported in that context previously to the best of our knowledge. Moreover, functional pathway analysis revealed that under low WSS conditions, several pathways regulating apoptosis are affected. In addition, KLF2 and KLF4, known atheroprotective genes, were downregulated under low WSS and upregulated under high WSS. KLF2 and VCAM1, both angiogenic, were upregulated under high WSS. NOS3, which is vascular protective, was also upregulated with higher WSS. On the contrary, ICAM-1 and E-selectin, both atherogenic and proinflammatory, were upregulated with high WSS. Collectively, the epigenetic landscape with the gene expression analysis reveals that low WSS is associated with a proapoptotic state, while high WSS is associated with a proliferative and proinflammatory state.

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.