Atrial fibrillation increases thrombogenicity of LVAD therapy.

BACKGROUND: This study investigates the hypothesis that presence of atrial fibrillation (AF) in LVAD patients increases thrombogenicity in the left ventricle (LV) and exacerbates stroke risk. METHODS: Using an anatomical LV model implanted with an LVAD inflow cannula, we analyze thrombogenic risk and blood flow patterns in either AF or sinus rhythm (SR) using unsteady computational fluid dynamics (CFD). To analyze platelet activation and thrombogenesis in the LV, hundreds of thousands of platelets are individually tracked to quantify platelet residence time (RT) and shear stress accumulation history (SH). RESULTS: The irregular and chaotic mitral inflow associated with AF results in markedly different intraventricular flow patterns, with profoundly negative impact on blood flow-induced stimuli experienced by platelets as they traverse the LV. Twice as many platelets accumulated very high SH in the LVAD + AF case, resulting in a 36% increase in thrombogenic potential score, relative to the LVAD + SR case. CONCLUSIONS: This supports the hypothesis that AF results in unfavorable blood flow patterns in the LV adding to an increased stroke risk for LVAD + AF patients. Quantification of thrombogenic risk associated with AF for LVAD patients may help guide clinical decision-making on interventions to mitigate the increased risk of thromboembolic events.

A Computational Investigation of the Effects of Temporal Synchronization of Left Ventricular Assist Device Speed Modulation with the Cardiac Cycle on Intraventricular Hemodynamics.

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.

Surface Reconstruction of the Pediatric Larynx via Structure from Motion Photogrammetry: A Pilot Study.

Endoscopy is the gold standard for characterizing pediatric airway disorders, however, it is limited for quantitative analysis due to lack of three-dimensional (3D) vision and poor stereotactic depth perception. We utilize structure from motion (SfM) photogrammetry, to reconstruct 3D surfaces of pathologic and healthy pediatric larynges from monocular two-dimensional (2D) endoscopy. Models of pediatric subglottic stenosis were 3D printed and airway endoscopies were simulated. 3D surfaces were successfully reconstructed from endoscopic videos of all models using an SfM analysis toolkit. Average subglottic surface error between SfM reconstructed surfaces and 3D printed models was 0.65 mm as measured by Modified Hausdorff Distance. Average volumetric similarity between SfM surfaces and printed models was 0.82 as measured by Jaccard Index. SfM can be used to accurately reconstruct 3D surface renderings of the larynx from 2D endoscopy video. This technique has immense potential for use in quantitative analysis of airway geometry and virtual surgical planning.

Hemodynamics of Saline Flushing in Endoscopic Imaging of Partially Occluded Coronary Arteries.

PURPOSE: Intravascular endoscopy can aid in the diagnosis of coronary atherosclerosis by providing direct color images of coronary plaques. The procedure requires a blood-free optical path between the catheter and plaque, and achieving clearance safely remains an engineering challenge. In this study, we investigate the hemodynamics of saline flushing in partially occluded coronary arteries to advance the development of intravascular forward-imaging catheters that do not require balloon occlusion. METHODS: In-vitro experiments and CFD simulations are used to quantify the influence of plaque size, catheter stand-off distance, saline injection flowrate, and injection orientation on the time required to achieve blood clearance. RESULTS: Experiments and simulation of saline injection from a dual-lumen catheter demonstrated that flushing times increase both as injection flow rate (Reynolds number) decreases and as the catheter moves distally away from the plaque. CFD simulations demonstrated that successful flushing was achieved regardless of lumen axial orientation in a 95% occluded artery. Flushing time was also found to increase as plaque size decreases for a set injection flowrate, and a lower limit for injection flowrate was found to exist for each plaques size, below which clearance was not achieved. For the three occlusion sizes investigated (90, 95, 97% by area), successful occlusion was achieved in less than 1.2 s. Investigation of the pressure fields developed during injection, highlight that rapid clearance can be achieved while keeping the arterial overpressure to < 1 mmHg. CONCLUSIONS: A dual lumen saline injection catheter was shown to produce clearance safely and effectively in models of partially occluded coronary arteries. Clearance was achieved across a range of engineering and clinical parameters without the use of a balloon occlusion, providing development guideposts for a fluid injection system in forward-imaging coronary endoscopes.

Fusiform versus Saccular Intracranial Aneurysms-Hemodynamic Evaluation of the Pre-Aneurysmal, Pathological, and Post-Interventional State.

Minimally-invasive therapies are well-established treatment methods for saccular intracranial aneurysms (SIAs). Knowledge concerning fusiform IAs (FIAs) is low, due to their wide and alternating lumen and their infrequent occurrence. However, FIAs carry risks like ischemia and thus require further in-depth investigation. Six patient-specific IAs, comprising three position-identical FIAs and SIAs, with the FIAs showing a non-typical FIA shape, were compared, respectively. For each model, a healthy counterpart and a treated version with a flow diverting stent were created. Eighteen time-dependent simulations were performed to analyze morphological and hemodynamic parameters focusing on the treatment effect (TE). The stent expansion is higher for FIAs than SIAs. For FIAs, the reduction in vorticity is higher (Δ35-75% case 2/3) and the reduction in the oscillatory velocity index is lower (Δ15-68% case 2/3). Velocity is reduced equally for FIAs and SIAs with a TE of 37-60% in FIAs and of 41-72% in SIAs. Time-averaged wall shear stress (TAWSS) is less reduced within FIAs than SIAs (Δ30-105%). Within this study, the positive TE of FDS deployed in FIAs is shown and a similarity in parameters found due to the non-typical FIA shape. Despite the higher stent expansion, velocity and vorticity are equally reduced compared to identically located SIAs.

Standardized viscosity as a source of error in computational fluid dynamic simulations of cerebral aneurysms.

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.

Solar-powered shape-changing origami microfliers.

Using wind to disperse microfliers that fall like seeds and leaves can help automate large-scale sensor deployments. Here, we present battery-free microfliers that can change shape in mid-air to vary their dispersal distance. We designed origami microfliers using bistable leaf-out structures and uncovered an important property: A simple change in the shape of these origami structures causes two dramatically different falling behaviors. When unfolded and flat, the microfliers exhibit a tumbling behavior that increases lateral displacement in the wind. When folded inward, their orientation is stabilized, resulting in a downward descent that is less influenced by wind. To electronically transition between these two shapes, we designed a low-power electromagnetic actuator that produces peak forces of up to 200 millinewtons within 25 milliseconds while powered by solar cells. We fabricated a circuit directly on the folded origami structure that includes a programmable microcontroller, a Bluetooth radio, a solar power-harvesting circuit, a pressure sensor to estimate altitude, and a temperature sensor. Outdoor evaluations show that our 414-milligram origami microfliers were able to electronically change their shape mid-air, travel up to 98 meters in a light breeze, and wirelessly transmit data via Bluetooth up to 60 meters away, using only power collected from the sun.

Improving the accuracy of computational fluid dynamics simulations of coiled cerebral aneurysms using finite element modeling.

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.

Towards Prediction of Blood Flow in Coiled Aneurysms Before Treatment: A Porous Media Approach.

Modeling blood flow in aneurysms treated with coils could be used to understand the complete embolization of the aneurysm, through thrombus formation that fills the entire sac. Modeling of the endovascular coil mass as a porous medium is a technique that allows for study of aneurysm hemodynamics, efficiently for patient-specific treatment outcome predictions. Models in the literature use mean porosity of coils in the aneurysmal volume, proving inadequate for outcome prediction. However, models that consider heterogeneous porosity distribution have shown more accurate hemodynamics. We recently published the porous crown model, considering the heterogeneous coil mass distribution, validated on two patients. This study aims (i) to validate the porous crown model for a larger cohort (eight patients), and (ii) to propose a porous medium model translatable to clinical practice in treatment planning. We analyzed the porosity distribution of the endovascular coils deployed inside the cerebral aneurysm phantoms of eight patients using 3D x-ray synchrotron images. The permeability and inertial factor of the porous crown model are calculated using previously published methodology. We propose a new "bilinear" porous model, that uses the same hypothesis, but the permeability and inertial factor can be defined from just basic information available in the neuro-suite, i.e., the aneurysmal sac volume and the coil volume fraction targeted by the neurosurgeon. These two models are compared to the coil-resolved simulations, considered as the gold standard. The results show that both the porous crown model and the bilinear model produce similarly accurate hemodynamics in the aneurysm. The error in the standard (mean porosity) porous model is 66%, whereas the error of the bilinear model is 26%, compared to the coil-resolved. The bilinear model is promising as a means of treatment outcome prediction at time of intervention.

In Vitro Investigation of the Effect of the Timing of Left Ventricular Assist Device Speed Modulation on Intraventricular Flow Patterns.

Thromboembolic events remain a common complication for left ventricular assist device (LVAD) patients. To prevent in-pump thrombosis, third-generation LVADs use speed modulation, which is not synchronized with the native left ventricle (LV) contractility. This study aims to investigate the effect of speed modulation on intraventricular flow patterns, and specifically, the impact of timing relative to pressure variations in the LV. Stereo-particle image velocimetry measurements were performed in a patient-derived LV implanted with an LVAD, for different timings of the speed modulation and speed. Speed modulation has a strong effect on instantaneous afterload and flowrate (-16% and +20%). The different timings of the speed modulation resulted in different flowrate waveforms, exhibiting different maxima (5.3-5.9 L/min, at constant average flowrate). Moreover, the timing of the speed modulation was found to strongly influence intraventricular flow patterns, specifically, stagnation areas within the LV. These experiments highlight, once more, the complex relationship between LVAD speed, hemodynamic resistance, and intraventricular pressure. Overall, this study demonstrates the importance of considering native LV contractility in future LVAD controls, to improve hemocompatibility and reduce the risk of thromboembolic complications.

Dialysate regeneration via urea photodecomposition with TiO2 nanowires at therapeutic rates.

BACKGROUND: The standard weekly treatment for end-stage renal disease patients is three 4-h-long hemodialysis sessions with each session c'onsuming over 120 L of clean dialysate, which prevents the development of portable or continuous ambulatory dialysis treatments. The regeneration of a small (~1 L) amount of dialysate would enable treatments that give conditions close to continuous hemostasis and improve patient quality of life through mobility. METHODS: Small-scale studies have shown that nanowires of TiO2 are highly efficient at photodecomposing urea into CO2 and N2 when using an applied bias and an air permeable cathode. To enable the demonstration of a dialysate regeneration system at therapeutically useful rates, a scalable microwave hydrothermal synthesis of single crystal TiO2 nanowires grown directly from conductive substrates was developed. These were incorporated into 1810 cm2 flow channel arrays. The regenerated dialysate samples were treated with activated carbon (2 min at 0.2 g/mL). RESULTS: The photodecomposition system achieved the therapeutic target of 14.2 g urea removal in 24 h. TiO2 electrode had a high urea removal photocurrent efficiency of 91%, with less than 1% of the decomposed urea generating NH4 + (1.04 µg/h/cm2 ), 3% generating NO3 - and 0.5% generating chlorine species. Activated carbon treatment could reduce total chlorine concentration from 0.15 to <0.02 mg/L. The regenerated dialysate showed significant cytotoxicity which could be removed by treatment with activated carbon. Additionally, a forward osmosis membrane with sufficient urea flux can cut off the mass transfer of the by-products back into the dialysate. CONCLUSION: Urea could be removed from spent dialysate at a therapeutic rate using a TiO2 based photooxidation unit, which can enable portable dialysis systems.

Analysis of Upper Airway Flow Dynamics in Robin Sequence Infants Using 4-D Computed Tomography and Computational Fluid Dynamics.

Robin Sequence (RS) is a potentially fatal craniofacial condition characterized by undersized jaw, posteriorly displaced tongue, and resultant upper airway obstruction (UAO). Accurate assessment of UAO severity is crucial for management and diagnosis of RS, yet current evaluation modalities have significant limitations and no quantitative measures of airway resistance exist. In this study, we combine 4-dimensional computed tomography and computational fluid dynamics (CFD) to assess, for the first time, UAO severity using fluid dynamic metrics in RS patients. Dramatic intrapopulation differences are found, with the ratio between most and least severe patients in breathing resistance, energy loss, and peak velocity equal to 40:1, 20:1, and 6:1, respectively. Analysis of local airflow dynamics characterized patients as presenting with primary obstructions either at the location of the tongue base, or at the larynx, with tongue base obstructions resulting in a more energetic stenotic jet and greater breathing resistance. Finally, CFD-derived flow metrics are found to correlate with the level of clinical respiratory support. Our results highlight the large intrapopulation variability, both in quantitative metrics of UAO severity (resistance, energy loss, velocity) and in the location and intensity of stenotic jets for RS patients. These results suggest that computed airflow metrics may significantly improve our understanding of UAO and its management in RS.

Modeling Flow in Cerebral Aneurysm After Coils Embolization Treatment: A Realistic Patient-Specific Porous Model Approach.

PURPOSE: Computational fluid dynamics (CFD) has been used to evaluate the efficiency of endovascular treatment in coiled cerebral aneurysms. The explicit geometry of the coil mass cannot typically be incorporated into CFD simulations since the coil mass cannot be reconstructed from clinical images due to its small size and beam hardening artifacts. The existing methods use imprecise porous medium representations. We propose a new porous model taking into account the porosity heterogeneity of the coils deployed in the aneurysm. METHODS: The porosity heterogeneity of the coil mass deployed inside two patients' cerebral aneurysm phantoms is first quantified based on 3D X-ray synchrotron images. These images are also used to compute the permeability and the inertial factor arising in porous models. A new homogeneous porous model (porous crowns model), considering the coil's heterogeneity, is proposed to recreate the flow within the coiled aneurysm. Finally, the validity of the model is assessed through comparisons with coil-resolved simulations. RESULTS: The strong porosity gradient of the coil measured close to the aneurysmal wall is well captured by the porous crowns model. The permeability and the inertial factor values involved in this model are closed to the ideal homogeneous porous model leading to a mean velocity in the aneurysmal sac similar as in the coil-resolved model. CONCLUSION: The porous crowns model allows for an accurate description of the mean flow within the coiled cerebral aneurysm.

Endothelial Responses to Curvature-Induced Flow Patterns in Engineered Cerebral Aneurysms.

Hemodynamic factors have long been associated with clinical outcomes in the treatment of cerebral aneurysms. Computational studies of cerebral aneurysm hemodynamics have provided valuable estimates of the mechanical environment experienced by the endothelium in both the parent vessel and aneurysmal dome walls and have correlated them with disease state. These computational-clinical studies have recently been correlated with the response of endothelial cells (EC) using either idealized or patient-specific models. Here, we present a robust workflow for generating anatomic-scale aneurysm models, establishing luminal cultures of ECs at physiological relevant flow profiles, and comparing EC responses to curvature mediated flow. We show that flow patterns induced by parent vessel curvature produce changes in wall shear stress (WSS) and wall shear stress gradients (WSSG) that are correlated with differences in cell morphology and cellular protein localization. Cells in higher WSS regions align better with the flow and display strong Notch1-extracellular domain (ECD) polarization, while, under low WSS, differences in WSSG due to curvature change were associated with less alignment and attenuation of Notch1-ECD polarization in ECs of the corresponding regions. These proof-of-concept results highlight the use of engineered cellularized aneurysm models for connecting computational fluid dynamics to the underlying endothelial biology that mediates disease.

Modeling the Mechanical Microenvironment of Coiled Cerebral Aneurysms.

Successful occlusion of cerebral aneurysms using coil embolization is contingent upon stable thrombus formation, and the quality of the thrombus depends upon the biomechanical environment. The goal of this study was to investigate how coil embolization alters the mechanical micro-environment within the aneurysm dome. Inertialess particles were injected in three-dimensional, computational simulations of flow inside patient aneurysms using patient-specific boundary conditions. Coil embolization was simulated as a homogenous porous medium of known permeability and inertial constant. Lagrangian particle tracking was used to calculate the residence time and shear stress history for particles in the flow before and after treatment. The percentage of particles entering the aneurysm dome correlated with the neck surface area before and after treatment (pretreatment: R2 = 0.831, P < 0.001; post-treatment: R2 = 0.638, P < 0.001). There was an inverse relationship between the change in particles entering the dome and coil packing density (R2 = 0.600, P < 0.001). Following treatment, the particles with the longest residence times tended to remain within the dome even longer while accumulating lower shear stress. A significant correlation was observed between the treatment effect on residence time and the ratio of the neck surface area to porosity (R2 = 0.390, P = 0.007). The results of this study suggest that coil embolization triggers clot formation within the aneurysm dome via a low shear stress-mediated pathway. This hypothesis links independently observed findings from several benchtop and clinical studies, furthering our understanding of this treatment strategy.

A Novel Patient-Specific Computational Fluid Dynamics Study of the Activation of Primary Collateral Pathways in the Circle of Willis During Vasospasm.

The Circle of Willis (CoW) is a redundant network of blood vessels that perfuses the brain. The ringlike anatomy mitigates the negative effects of stroke by activating collateral pathways that help maintain physiological perfusion. Previous studies have investigated the activation of these pathways during embolic stroke and internal carotid artery occlusion. However, the role of collateral pathways during cerebral vasospasm-an involuntary constriction of blood vessels after subarachnoid hemorrhage-is not well-documented. This study presents a novel technique to create patient-specific computational fluid dynamics (CFD) simulations of the Circle of Willis before and during vasospasm. Computed tomographic angiography (CTA) scans are segmented to model the vasculature, and transcranial Doppler ultrasound (TCD) measurements of blood flow velocity are applied as boundary conditions. Bayesian analysis leverages information about the uncertainty in the measurements of vessel diameters and velocities to find an optimized parameter set that satisfies mass conservation and that is applied in the final simulation. With this optimized parameter set, the diameters, velocities, and flow rates fall within typical literature values. Virtual angiograms modeled using passive scalar transport agree closely with clinical angiography. A sensitivity analysis quantifies the changes in collateral flow rates with respect to changes in the inlet and outlet flow rates. This analysis can be applied in the future to a cohort of patients to investigate the relationship between the locations and severities of vasospasm, the patient-to-patient anatomical variability in the Circle of Willis, and the activation of collateral pathways.

Patient-specific computational fluid dynamic simulation of cerebrospinal fluid flow in the intracranial space.

BACKGROUND: Abnormal cerebrospinal fluid (CSF) flow is associated with a variety of poorly understood neurological disorders such as Alzheimer's Disease and hydrocephalus. The lack of comprehensive understanding of the fluid and solid mechanics of CSF flow remains a critical barrier in the development of diagnostic assessment and potential treatment options for these diseases. We have developed a whole brain, patient-specific computational fluid dynamics (CFD) simulation of CSF flow in the cranial cavity as a step towards comprehensive understanding of CSF dynamics and how they relate to neurodegenerative diseases. METHODS: A patient-specific 3D geometry of the CSF filled spaces was segmented from structural MRI. Patient-specific boundary conditions were measured using phase contrast MRI. A rigid wall three-dimensional CFD simulation was conducted using only patient-specific waveforms as boundary conditions. Deformation of brain tissue is accounted for using volumetric flowrate boundary conditions calculated via the conservation of mass. Phase contrast MRI measurement of maximum velocity at the cerebral aqueduct was used to validate the simulation with excellent agreement. RESULTS: The CSF dynamics across the cardiac cycle are presented, illustrating the relationship between arterial flow and CSF flow. Flow in and out of the ventricles was shown to have a slight phase delay (∼20 % of the cardiac cycle) from flow in the subarachnoid space. Intracranial pressure dynamics are presented, with pressure in the Lateral Ventricles demonstrating less significant transient effects than pressure in the subarachnoid space. CONCLUSIONS: This work presents a quantitatively validated whole-brain simulation of CSF flow for a single healthy subject. The computational methodology improves over the state of the art by eliminating non-physiological boundary conditions and unnecessary assumptions about the mechanical properties of brain tissue, providing an essential step towards clinically useful tools for assessing the development of neurodegenerative disorders.

A Computational Hemodynamics Approach to Left Ventricular Assist Device (LVAD) Optimization Validated in a Large Patient Cohort.

With increasing use of left ventricular assist devices (LVAD) it is critical to devise strategies to optimize LVAD speed while controlling mean arterial pressure (MAP) and flow according to patient physiology. The complex interdependency between LVAD speed, MAP, and flow frequently makes optimization difficult under clinical conditions. We propose a method to guide this procedure in silico, narrowing the conditions to test clinically. A computational model of the circulatory network that simulates HF and LVAD support, incorporating LVAD pressure-flow curves was applied retrospectively to anonymized patient hemodynamics data from the University of Washington Medical Center. MAP management on 61 patient-specific computational models with a target of 70 mm Hg, resulting flow for a given LVAD speed was analyzed, and compared to a target output of 5 L/min. Before performing virtual MAP management, 51% had a MAP>70 mm Hg and CO>5 L/min, and 33% had a MAP>70 mm Hg and CO<5 L/min. After changing systemic resistance to meet the MAP target (without adjusting LVAD speed), 84% of cases resulted in CO higher than 5 L/min, with a median CO of 6.79 L/min, using the computational predictive model. Blood pressure management alone is insufficient in meeting both MAP and CO targets, due to the risk of hypervolemia, and requires appropriate LVAD speed optimization to achieve both targets, while preserving right heart health. Such computational tools can narrow down conditions to be tested for each patient, providing significant insight into the pump-patient interplay. LVAD hemodynamic optimization has the potential to reduce complications and improve outcomes.

The effect of Dean, Reynolds and Womersley numbers on the flow in a spherical cavity on a curved round pipe. Part 2. The haemodynamics of intracranial aneurysms treated with flow-diverting stents.

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 ≈ 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.

Optimization Study of the Hemodynamics of Saline Flushing in Endoscopic Imaging of Chronic Total Occlusions (CTOs).

PURPOSE: In this study, in vitro experiments and computational fluid dynamic (CFD) simulations are used to expand the understand of the physics of saline flushing of a blocked artery to enable optical imaging. This process involves saline injection, mixing with blood, and advection of the mixture away from the region of interest to provide a clear optical path for imaging. METHODS: CFD simulations are used as a rapid turn-around tool for the evolutionary design process of an endovascular catheter that combines imaging forward-viewing element with saline flushing lumens. RESULTS: A novel design and control technique is developed that provides the method to regulate the pressure in a blocked artery during saline flushing, so only small deviations from physiological pressure values are exerted on the damaged artery wall at any time, minimizing risk of rupture. In vitro experiments demonstrate the optical clearing process in phantoms simulating chronic total occlusions (CTOs) in coronary arteries with an opaque blood surrogate being removed by saline flushing. With the CFD compared by the experiments, parametric analyses of artery diameter and curvature, and flushing lumen diameter size were conducted to understand their impact on flushing times and pressures. Different plaque morphologies were studied to explore the feasibility of saline flushing in different CTO conditions. CONCLUSIONS: A new catheter design is demonstrated to safely and effectively produce saline flushing, leading to a clear optical imaging field, and an improved technique is outlined that overcomes some practical challenges and limitations commonly encountered in angioscopy.