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.

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.

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.

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.

The effect of Dean, Reynolds, and Womersley number on the flow in a spherical cavity on a curved round pipe. Part 1. Fluid mechanics in the cavity as a canonical flow representing intracranial aneurysms.

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 De, combining the effects of Reynolds number, Re, and of the curvature along the pipe centreline, κ. Pulsatility in the flow introduces a dependency on the Womersley number Wo. Using stereo PIV 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 κ and Re, 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 Re and the Wo 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.

Lagrangian Trajectory Simulation of Platelets and Synchrotron Microtomography Augment Hemodynamic Analysis of Intracranial Aneurysms Treated With Embolic Coils.

As frequency of endovascular treatments for intracranial aneurysms increases, there is a growing need to understand the mechanisms for coil embolization failure. Computational fluid dynamics (CFD) modeling often simplifies modeling the endovascular coils as a homogeneous porous medium (PM), and focuses on the vascular wall endothelium, not considering the biomechanical environment of platelets. These assumptions limit the accuracy of computations for treatment predictions. We present a rigorous analysis using X-ray microtomographic imaging of the coils and a combination of Lagrangian (platelet) and Eulerian (endothelium) metrics. Four patient-specific, anatomically accurate in vitro flow phantoms of aneurysms are treated with the same patient-specific endovascular coils. Synchrotron tomography scans of the coil mass morphology are obtained. Aneurysmal hemodynamics are computationally simulated before and after coiling, using patient-specific velocity/pressure measurements. For each patient, we analyze the trajectories of thousands of platelets during several cardiac cycles, and calculate residence times (RTs) and shear exposure, relevant to thrombus formation. We quantify the inconsistencies of the PM approach, comparing them with coil-resolved (CR) simulations, showing the under- or overestimation of key hemodynamic metrics used to predict treatment outcomes. We fully characterize aneurysmal hemodynamics with converged statistics of platelet RT and shear stress history (SH), to augment the traditional wall shear stress (WSS) on the vascular endothelium. Incorporating microtomographic scans of coil morphology into hemodynamic analysis of coiled intracranial aneurysms, and augmenting traditional analysis with Lagrangian platelet metrics improves CFD predictions, and raises the potential for understanding and clinical translation of computational hemodynamics for intracranial aneurysm treatment outcomes.

Platelet Dynamics and Hemodynamics of Cerebral Aneurysms Treated with Flow-Diverting Stents.

Flow-diverting stents (FDS) are used to treat cerebral aneurysms. They promote the formation of a stable thrombus within the aneurysmal sac and, if successful, isolate the aneurysmal dome from mechanical stresses to prevent rupture. Platelet activation, a mechanism necessary for thrombus formation, is known to respond to biomechanical stimuli, particularly to the platelets' residence time and shear stress exposure. Currently, there is no reliable method for predicting FDS treatment outcomes, either a priori or after the procedure. Eulerian computational fluid dynamic (CFD) studies of aneurysmal flow have searched for predictors of endovascular treatment outcome; however, the hemodynamics of thrombus formation cannot be fully understood without considering the platelets' trajectories and their mechanics-triggered activation. Lagrangian analysis of the fluid mechanics in the aneurysmal vasculature provides novel metrics by tracking the platelets' residence time (RT) and shear history (SH). Eulerian and Lagrangian parameters are compared for 19 patient-specific cases, both pre- and post-treatment, to assess the degree of change caused by the FDS and subsequent treatment efficacy.

Reconstructing patient-specific cerebral aneurysm vasculature for in vitro investigations and treatment efficacy assessments.

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.

Computational fluid dynamics of cerebral aneurysm coiling using high-resolution and high-energy synchrotron X-ray microtomography: comparison with the homogeneous porous medium approach.

BACKGROUND: Computational modeling of intracranial aneurysms provides insights into the influence of hemodynamics on aneurysm growth, rupture, and treatment outcome. Standard modeling of coiled aneurysms simplifies the complex geometry of the coil mass into a homogeneous porous medium that fills the aneurysmal sac. We compare hemodynamics of coiled aneurysms modeled from high-resolution imaging with those from the same aneurysms modeled following the standard technique, in an effort to characterize sources of error from the simplified model. MATERIALS: Physical models of two unruptured aneurysms were created using three-dimensional printing. The models were treated with coil embolization using the same coils as those used in actual patient treatment and then scanned by synchrotron X-ray microtomography to obtain high-resolution imaging of the coil mass. Computational modeling of each aneurysm was performed using patient-specific boundary conditions. The coils were modeled using the simplified porous medium or by incorporating the X-ray imaged coil surface, and the differences in hemodynamic variables were assessed. RESULTS: X-ray microtomographic imaging of coils and incorporation into computational models were successful for both aneurysms. Porous medium calculations of coiled aneurysm hemodynamics overestimated intra-aneurysmal flow, underestimated oscillatory shear index and viscous dissipation, and over- or underpredicted wall shear stress (WSS) and WSS gradient compared with X-ray-based coiled computational fluid dynamics models. CONCLUSIONS: Computational modeling of coiled intracranial aneurysms using the porous medium approach may inaccurately estimate key hemodynamic variables compared with models incorporating high-resolution synchrotron X-ray microtomographic imaging of complex aneurysm coil geometry.

Convective Leakage Makes Heparin Locking of Central Venous Catheters Ineffective Within Seconds: Experimental Measurements in a Model Superior Vena Cava.

Central venous catheters (CVCs), placed in the superior vena cava (SVC) for hemodialysis or chemotherapy, are routinely filled while not in use with heparin, an anticoagulant, to maintain patency and prevent thrombus formation at the catheter tip. The heparin-locking procedure, however, places the patient at risk for systemic bleeding, as heparin is known to leak from the catheter into the blood stream. We provide evidence from detailed in vitro experiments that shows the driving mechanism behind heparin leakage to be convective-diffusive transport due to the pulsatile flow surrounding the catheter. This novel mechanism is supported by experimental planar laser-induced fluorescence (PLIF) and particle image velocimetry (PIV) measurements of flow velocity and heparin transport from a CVC placed inside a model SVC inside a pulsatile flow loop. The results predict an initial, fast (<10 s), convection-dominated phase that rapidly depletes the concentration of heparin in the near-tip region, the region of the catheter with side holes. This is followed by a slow, diffusion-limited phase inside the catheter lumen, where the concentration is still high, that is insufficient at replenishing the lost heparin concentration in the near-tip region. The results presented here, which are consistent with previous in vivo estimates of 24 hour leakage rates, predict that the concentration of heparin in the near-tip region is essentially zero for the majority of the interdialytic phase, rendering the heparin locking procedure ineffective.

Accuracy of computational cerebral aneurysm hemodynamics using patient-specific endovascular measurements.

Computational hemodynamic simulations of cerebral aneurysms have traditionally relied on stereotypical boundary conditions (such as blood flow velocity and blood pressure) derived from published values as patient-specific measurements are unavailable or difficult to collect. However, controversy persists over the necessity of incorporating such patient-specific conditions into computational analyses. We perform simulations using both endovascularly-derived patient-specific and typical literature-derived inflow and outflow boundary conditions. Detailed three-dimensional anatomical models of the cerebral vasculature are developed from rotational angiography data, and blood flow velocity and pressure are measured in situ by a dual-sensor pressure and velocity endovascular guidewire at multiple peri-aneurysmal locations in 10 unruptured cerebral aneurysms. These measurements are used to define inflow and outflow boundary conditions for computational hemodynamic models of the aneurysms. The additional in situ measurements which are not prescribed in the simulation are then used to assess the accuracy of the simulated flow velocity and pressure drop. Simulated velocities using patient-specific boundary conditions show good agreement with the guidewire measurements at measurement locations inside the domain, with no bias in the agreement and a random scatter of ≈25%. Simulated velocities using the simplified, literature-derived values show a systematic bias and over-predicted velocity by ≈30% with a random scatter of ≈40%. Computational hemodynamics using endovascularly measured patient-specific boundary conditions have the potential to improve treatment predictions as they provide more accurate and precise results of the aneurysmal hemodynamics than those based on commonly accepted reference values for boundary conditions.