Flow in sidewall cerebral aneurysms can be ideally modelled as the combination of flow over a spherical cavity and flow in a curved circular pipe, two canonical flows. Flow in a curved pipe is known ...to depend on the Dean number $De$, combining the effects of Reynolds number $\textit {Re}$ and of the curvature along the pipe centreline, $\kappa$. Pulsatility in the flow introduces a dependence on the Womersley number $Wo$. Using stereo particle image velocimetry measurements, this study investigated the effect of these three key non-dimensional parameters, by modifying pipe curvature ($De$), flow rate ($Re$) and pulsatility frequency ($Wo$), on the flow patterns in a spherical cavity. A single counter-rotating vortex was observed in the cavity for all values of pipe curvature $\kappa$ and Reynolds number $\textit {Re}$, for both steady and pulsatile inflow conditions. Increasing the pipe curvature impacted the flow patterns in both the pipe and the cavity, by shifting the velocity profile towards the cavity opening and increasing the flow rate in to the cavity. The circulation in the cavity was found to collapse well with only the Dean number, for both steady and pulsatile inflows. For pulsatile inflow, the counter-rotating vortex was unstable and the location of its centre over time was impacted by the curvature of the pipe, as well as $\textit {Re}$ and $Wo$ in the free stream. The circulation in the cavity was higher for steady inflow than for the equivalent average Reynolds number and Dean number pulsatile inflow, with very limited impact of the Womersley number in the range studied. A second part of this study, that focuses on the changes in fluid dynamics when the intracranial aneurysm is treated with a flow-diverting stent, can be found in this issue (Barbour et al., J. Fluid Mech., vol. 915, 2021, A124).
Patients with advanced heart failure are implanted with a left ventricular assist device (LVAD) as a bridge-to-transplantation or destination therapy. Despite advances in pump design, the risk of ...stroke remains high. LVAD implantation significantly alters intraventricular hemodynamics, where regions of stagnation or elevated shear stresses promote thrombus formation. Third generation pumps incorporate a pulsatility mode that modulates rotational speed of the pump to enhance in-pump washout. We investigated how the timing of the pulsatility mode with the cardiac cycle affects intraventricular hemodynamic factors linked to thrombus formation. Computational fluid dynamics simulations with Lagrangian particle tracking to model platelet behavior in a patient-specific left ventricle captured altered intraventricular hemodynamics due to LVAD implantation. HeartMate 3 incorporates a pulsatility mode that modulates the speed of the pump every two seconds. Four different timings of this pulsatility mode with respect to the cardiac cycle were investigated. A strong jet formed between the mitral valve and inflow cannula. Blood stagnated in the left ventricular outflow tract beneath a closed aortic valve, in the near-wall regions off-axis of the jet, and in a large counterrotating vortex near the anterior wall. Computational results showed good agreement with particle image velocimetry results. Synchronization of the pulsatility mode with peak systole decreased stasis, reflected in the intraventricular washout of virtual contrast and Lagrangian particles over time. Temporal synchronization of HeartMate 3 pulsatility with the cardiac cycle reduces intraventricular stasis and could be beneficial for decreasing thrombogenicity.
The Circle of Willis (CoW) is a ring-like network of blood vessels that perfuses the brain. Flow in the collateral pathways that connect major arterial inputs in the CoW change dynamically in ...response to vessel narrowing or occlusion. Vasospasm is an involuntary constriction of blood vessels following subarachnoid hemorrhage (SAH), which can lead to stroke. This study investigated interactions between localization of vasospasm in the CoW, vasospasm severity, anatomical variations, and changes in collateral flow directions. Patient-specific computational fluid dynamics (CFD) simulations were created for 25 vasospasm patients. Computed tomographic angiography scans were segmented capturing the anatomical variation and stenosis due to vasospasm. Transcranial Doppler ultrasound measurements of velocity were used to define boundary conditions. Digital subtraction angiography was analyzed to determine the directions and magnitudes of collateral flows as well as vasospasm severity in each vessel. Percent changes in resistance and viscous dissipation were analyzed to quantify vasospasm severity and localization of vasospasm in a specific region of the CoW. Angiographic severity correlated well with percent changes in resistance and viscous dissipation across all cerebral vessels. Changes in flow direction were observed in collateral pathways of some patients with localized vasospasm, while no significant changes in flow direction were observed in others. CFD simulations can be leveraged to quantify the localization and severity of vasospasm in SAH patients. These factors as well as anatomical variation may lead to changes in collateral flow directions. Future work could relate localization and vasospasm severity to clinical outcomes like the development of infarct.
Background
Computational fluid dynamics (CFD) simulations are a powerful tool for studying cerebral aneurysms, capable of evaluating hemodynamics in a way that is infeasible with imaging alone. ...However, the difficulty of incorporating patient‐specific information and inherent obstacles of in vivo validation have limited the clinical usefulness of CFD of cerebral aneurysms. In this work we investigate the effect of using standardized blood viscosity values in CFD simulations of cerebral aneurysms when compared to simulations of the same aneurysms using patient‐specific viscosity values derived from hematocrit measurements.
Purpose
The objective of this work is to determine the level of error, on average, that is, caused by using standardized values of viscosity in CFD simulations of cerebral aneurysms. By quantifying this error, we demonstrate the need for incorporating patient‐specific viscosity in future CFD investigations of cerebral aneurysms.
Methods
CFD simulations of forty‐one cerebral aneurysms were conducted using patient‐specific boundary conditions. For each aneurysm two simulations were conducted, one utilizing patient‐specific blood viscosity derived from hematocrit measurements and another using a standardized value for blood viscosity. Hemodynamic parameters such as wall shear stress (WSS), wall shear stress gradient (WSSG), and the oscillatory shear index (OSI) were calculated for each of the simulations for each aneurysm. Paired t‐tests for differences in the time‐averaged maps of these hemodynamic parameters between standardized and patient‐specific viscosity simulations were conducted for each aneurysm. Bland–Altman analysis was used to examine the cohort‐wide changes in the hemodynamic parameters. Subjects were broken into two groups, those with higher than standard viscosity and those with lower than standard viscosity. An unpaired t‐test was used to compare the percent change in WSS, WSSG, and OSI between patient‐specific and standardized viscosity simulations for the two cohorts. The percent changes in hemodynamic parameters were correlated against the direction and magnitude of percent change in viscosity, aneurysm size, and aneurysm location. For all t‐tests, a Bonferroni‐corrected significance level of 0.0167 was used.
Results
63.2%, 41.5%, and 48.7% of aneurysms showed statistically significant differences between patient‐specific and standardized viscosity simulations for WSS, WSSG, and OSI respectively. No statistically significant difference was found in the percent changes in WSS, WSSG, and OSI between the group with higher than standard viscosity and those with lower than standard viscosity, indicating an increase in viscosity can cause either an increase or decrease in each of the hemodynamic parameters. On a study‐wide level no significant bias was found in either direction for WSS, WSSG, or OSI between the simulation groups due to the bidirectional effect of changing viscosity. No correlation was found between percent change of viscosity and percent change of WSS, WSSG, or OSI, meaning an after‐the‐fact correction for patient‐specific viscosity is not feasible.
Conclusion
Standardizing viscosity values in CFD of cerebral aneurysms has a large and unpredictable impact on the calculated WSS, WSSG, and OSI when compared to CFD simulations of the same aneurysms using a patient‐specific viscosity. We recommend implementing hematocrit‐based patient‐specific blood viscosity values for all CFD simulations of cerebral aneurysms.
Increased maternal body mass index (BMI) is a robust risk factor for later pediatric obesity. Accumulating evidence suggests that human milk (HM) may attenuate the transfer of obesity from mother to ...offspring, potentially through its effects on early development of the infant microbiome.
Our objective was to identify early differences in intestinal microbiota in a cohort of breastfeeding infants born to obese compared with normal-weight (NW) mothers. We also investigated relations between HM hormones (leptin and insulin) and both the taxonomic and functional potentials of the infant microbiome.
Clinical data and infant stool and fasting HM samples were collected from 18 NW prepregnancy BMI (in kg/m(2)) <24.0 and 12 obese (prepregnancy BMI >30.0) mothers and their exclusively breastfed infants at 2 wk postpartum. Infant body composition at 2 wk was determined by air-displacement plethysmography. Infant gastrointestinal microbes were estimated by using 16S amplicon and whole-genome sequencing. HM insulin and leptin were determined by ELISA; short-chain fatty acids (SCFAs) were measured in stool samples by using gas chromatography. Power was set at 80%.
Infants born to obese mothers were exposed to 2-fold higher HM insulin and leptin concentrations (P < 0.01) and showed a significant reduction in the early pioneering bacteria Gammaproteobacteria (P = 0.03) and exhibited a trend for elevated total SCFA content (P < 0.06). Independent of maternal prepregnancy BMI, HM insulin was positively associated with both microbial taxonomic diversity (P = 0.03) and Gammaproteobacteria (e.g., Enterobacteriaceae; P = 0.04) and was negatively associated with Lactobacillales (e.g., Streptococcaceae; P = 0.05). Metagenomic analysis showed that HM leptin and insulin were associated with decreased bacterial proteases, which are implicated in intestinal permeability, and reduced concentrations of pyruvate kinase, a biomarker of pediatric gastrointestinal inflammation.
Our results indicate that, although maternal obesity may adversely affect the early infant intestinal microbiome, HM insulin and leptin are independently associated with beneficial microbial metabolic pathways predicted to increase intestinal barrier function and reduce intestinal inflammation. This trial was registered at clinicaltrials.gov as NCT01693406.
The flow in a spherical cavity on a curved round pipe is a canonical flow that describes well the flow inside a sidewall aneurysm on an intracranial artery. Intracranial aneurysms are often treated ...with a flow-diverting stent (FDS), a low-porosity metal mesh that covers the entrance to the cavity, to reduce blood flow into the aneurysm sac and exclude it from mechanical stresses imposed by the blood flow. Successful treatment is highly dependent on the degree of reduction of flow inside the cavity, and the resulting altered fluid mechanics inside the aneurysm following treatment. Using stereoscopic particle image velocimetry, we characterize the fluid mechanics in a canonical configuration representative of an intracranial aneurysm treated with a FDS: a spherical cavity on the side of a curved round pipe covered with a metal mesh formed by an actual medical FDS. This porous mesh coverage is the focus of Part 2 of the paper, characterizing the effects of parent vessel $Re$, $De$ and pulsatility, $Wo$, on the fluid dynamics, compared with the canonical configuration with no impediments to flow into the cavity that is described in Part 1 (Chassagne et al., J. Fluid Mech., vol. 915, 2021, A123). Coverage with a FDS markedly reduces the flow $Re$ in the aneurysmal cavity, creating a viscous-dominated flow environment despite the parent vessel $Re>100$. Under steady flow conditions, the topology that forms inside the cavity is shown to be a function of the parent vessel $De$. At low values of $De$, flow enters the cavity at the leading edge and remains attached to the wall before exiting at the trailing edge, a novel behaviour that was not found under any conditions of the high-$Re$, unimpeded cavity flow described in Part 1. Under these conditions, flow in the cavity co-rotates with the direction of the free-stream flow, similar to Stokes flow in a cavity. As $De$ increases, the flow along the leading edge begins to separate, and the recirculation zone grows with increasing $De$, until, above $De \approx 180$, the flow inside the cavity is fully recirculating, counter-rotating with respect to the free-stream flow. Under pulsatile flow conditions, the vortex inside the cavity progresses through the same cycle – switching from attached and co-rotating with the free-stream flow at the beginning of the cycle (low velocity and positive acceleration) to separated and counter-rotating as $De$ reaches a critical value. The location of separation within the harmonic cycle is shown to be a function of both $De$ and $Wo$. The values of aneurysmal cavity $Re$ based on both the average velocity and the circulation inside the cavity are shown to increase with increasing values of $De$, while $Wo$ is shown to have little influence on the time-averaged metrics. As $De$ increases, the strength of the secondary flow in the parent vessel grows, due to the inertial instability in the curved pipe, and the flow rate entering the cavity increases. Thus, the effectiveness of FDS treatment to exclude the aneurysmal cavity from the haemodynamic stresses is compromised for aneurysms located on high-curvature arteries, i.e. vessels with high $De$, and this can be a fluid mechanics criterion to guide treatment selection.
Cerebral aneurysms are a serious clinical challenge, with ∼half resulting in death or disability. Treatment via endovascular coiling significantly reduces the chances of rupture, but the techniquehas ...failure rates of ∼20 %. This presents a pressing need to develop a method fordetermining optimal coildeploymentstrategies. Quantification of the hemodynamics of coiled aneurysms using computational fluid dynamics (CFD) has the potential to predict post-treatment outcomes, but representing the coil mass in CFD simulations remains a challenge. We use the Finite Element Method (FEM) for simulating patient-specific coil deployment for n = 4 ICA aneurysms for which 3D printed in vitro models were also generated, coiled, and scanned using ultra-high resolution synchrotron micro-CT. The physical and virtual coil geometries were voxelized onto a binary structured grid and porosity maps were generated for geometric comparison. The average binary accuracy score is 0.8623 and the average error in porosity map is 4.94 %. We then conduct patient-specific CFD simulations of the aneurysm hemodynamics using virtual coils geometries, micro-CT generated oil geometries, and using the porous medium method to represent the coil mass. Hemodynamic parameters including Neck Inflow Rate (Qneck) and Wall Shear Stress (WSS) were calculated for each of the CFD simulations. The average relative error in Qneck and WSS from CFD using FEM geometry were 6.6 % and 21.8 % respectively, while the error from CFD using a porous media approximation resulted in errors of 55.1 % and 36.3 % respectively; demonstrating a marked improvement in the accuracy of CFD simulations using FEM generated coil geometries.
Objective
To determine the risk of all‐cause and disease‐specific mortality among older women with hip osteoarthritis (OA) and to identify mediators in the causal pathway.
Methods
Data were from the ...Study of Osteoporotic Fractures, a US population‐based cohort study of 9,704 white women age ≥65 years. The analytic sample included women with hip radiographs at baseline (n = 7,889) and year 8 (n = 5,749). Mortality was confirmed through October 2013 by death certificates and hospital discharge summaries. Radiographic hip OA (RHOA) was defined as a Croft grade of ≥2 in at least 1 hip (definite joint space narrowing or osteophytes plus 1 other radiographic feature).
Results
The mean ± SD followup time was 16.1 ± 6.2 years. The baseline and year 8 prevalence of RHOA were 8.0% and 11.0%, respectively. The cumulative incidence (proportion of deaths during the study period) was 67.7% for all‐cause mortality, 26.3% for cardiovascular disease (CVD) mortality, 11.7% for cancer mortality, 1.9% for gastrointestinal disease mortality, and 27.8% for all other mortality causes. RHOA was associated with an increased risk of all‐cause mortality (hazard ratio 1.14 95% confidence interval 1.05–1.24) and CVD mortality (hazard ratio 1.24 95% confidence interval 1.09–1.41) adjusted for age, body mass index, education, smoking, health status, diabetes, and stroke. These associations were partially explained by the mediating variable of physical function.
Conclusion
RHOA was associated with an increased risk of all‐cause and CVD mortality among older white women followed up for 16 years. Dissemination of evidence‐based physical activity and self‐management interventions for hip OA in community and clinical settings can improve physical function and might also contribute to lower mortality.
Flow in side-wall cerebral aneurysms can be ideally modelled as the combination of flow over a spherical cavity and flow in a curved circular pipe, two canonical flows. Flow in a curved pipe is known ...to depend on the Dean number
, combining the effects of Reynolds number,
, and of the curvature along the pipe centreline,
. Pulsatility in the flow introduces a dependency on the Womersley number
. Using stereo PIV measurements, this study investigated the effect of these three key non-dimensional parameters, by modifying pipe curvature (
), flow-rate (
), and pulsatility frequency (
), on the flow patterns in a spherical cavity. A single counter-rotating vortex was observed in the cavity for all values of pipe curvature
and
, for both steady and pulsatile inflow conditions. Increasing the pipe curvature impacted both the flow patterns in the pipe and the cavity, by shifting the velocity profile towards the cavity opening and increasing the flow rate into the cavity. The circulation in the cavity was found to collapse well with only the Dean number, for both steady and pulsatile inflows. For pulsatile inflow, the counter-rotating vortex was unstable and the location of its centre over time was impacted by the curvature of the pipe, as well as the
and the
in the freestream. The circulation in the cavity was higher for steady inflow than for the equivalent average Reynolds and Dean number pulsatile inflow, with very limited impact of the Womersley in the range studied.
•Aneurysmal hemodynamics are helpful in treatment planning and prediction.•In vitro models can validate patient-specific computational simulations of aneurysms.•Dimensionally-accurate, ...optically-transparent phantoms can be done by 3D printing.•Such models may inform optimal patient-specific neurointerventional strategies.
Perianeurysmal hemodynamics play a vital role in the initiation, growth and rupture of intracranial aneurysms. In vitro investigations of aneurysmal hemodynamics are helpful to visualize and measure blood flow, and aiding surgical planning approaches. Improving in vitro model creation can improve the feasibility and accuracy of hemodynamic investigations and surgical planning, improving clinical value. In this study, in vitro models were created from three-dimensional rotational angiography (3DRA) of six patients harboring intracranial aneurysms using a multi-step process involving 3D printing, index of refraction matching and silicone casting that renders the models transparent for flow visualization. Each model was treated with the same commercially-available, patient-specific, endovascular devices (coils and/or stents). All models were scanned by synchrotron X-ray microtomography to obtain high-resolution imaging of the vessel lumen, aneurysmal sac and endovascular devices. Dimensional accuracy was compared by quantifying the differences between the microtomographic reconstructions of the fabricated phantoms and the original 3DRA obtained during patient treatment. True-scale in vitro flow phantoms were successfully created for all six patients. Optical transparency was verified by using an index of refraction matched working fluid that replicated the mechanical behavior of blood. Synchrotron imaging of vessel lumen, aneurysmal sac and endovascular devices was successfully obtained, and dimensional errors were found to be O(100 μm). The creation of dimensionally-accurate, optically-transparent flow phantoms of patient-specific intracranial aneurysms is feasible using 3D printing technology. Such models may enable in vitro investigations of aneurysmal hemodynamics to aid in treatment planning and outcome prediction to devise optimal patient-specific neurointerventional strategies.
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