Embolus Transport Simulations with Fully Resolved Particle Surfaces.

PURPOSE: There has been interest in recent work in using computational fluid dynamics with Lagrangian analysis to calculate the trajectory of emboli-like particles in the vasculature. While previous studies have provided an understanding of the hemodynamic factors determining the fates of such particles and their relationship to risk of stroke, most analyses have relied on a particle equation of motion that assumes the particle is "small" e.g., much less than the diameter of the vessel. This work quantifies the limit when a particle can no longer be considered "small". METHODS: The motion of embolus-like particles are simulated using an overset mesh technique. This allows the fluid stresses on the particle surface to be fully resolved. Consequently, the particles can be of arbitrary size or shape. The trajectory of resolved particles and "small" particles are simulated through a patient-specific carotid artery bifurcation model with particles 500, 1000, and 2000 µm in diameter. The proportions of particles entering the internal carotid artery are treated as the outcome of the particle fate, and statistical comparisons are made to ascertain the importance of non-small particle effects. RESULTS: For the 2000 µm embolus, the proportion of particles traveling to the internal carotid artery is 74.7 ± 1.3% (mean ± 95% confidence margin) for the "small" particle model and is 85.7 ± 5.4% for a resolved particle model. The difference is statistically significant, [Formula: see text], based on the binomial test for the particle outcomes. No statistically discernible differences are found for the smaller diameter particles. CONCLUSIONS: Quantitative differences are observable for the 2000 µm trajectories between the "small" and resolved particle models which is a particle diameter 27% relative to the common carotid artery diameter. A fully resolved particle model ought to be considered for emboli trajectory simulations when the particle size ratio is ≳ 20%.

Intermittent Aortic Valve Opening and Risk of Thrombosis in Ventricular Assist Device Patients.

The current study evaluates quantitatively the impact that intermittent aortic valve (AV) opening has on the thrombogenicity in the aortic arch region for patients under left ventricular assist device (LVAD) therapy. The influence of flow through the AV, opening once every five cardiac cycles, on the flow patterns in the ascending aortic is measured in a patient-derived computed tomography image-based model, after LVAD implantation. The mechanical environment of flowing platelets is investigated, by statistical treatment of outliers in Lagrangian particle tracking, and thrombogenesis metrics (platelet residence times and activation state characterized by shear stress accumulation) are compared for the cases of closed AV versus intermittent AV opening. All hemodynamics metrics are improved by AV opening, even at a reduced frequency and flow rate. Residence times of platelets or microthrombi are reduced significantly by transvalvular flow, as are the shear stress history experienced and the shear stress magnitude and gradients on the aortic root endothelium. The findings of this device-neutral study support the multiple advantages of management that enables AV opening, providing a rationale for establishing this as a standard in long-term treatment and care for advanced heart failure patients.

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.

LVAD Outflow Graft Angle and Thrombosis Risk.

This study quantifies thrombogenic potential (TP) of a wide range of left ventricular assist device (LVAD) outflow graft anastomosis angles through state-of-the-art techniques: 3D imaged-based patient-specific models created via virtual surgery and unsteady computational fluid dynamics with Lagrangian particle tracking. This study aims at clarifying the influence of a single parameter (outflow graft angle) on the thrombogenesis associated with flow patterns in the aortic root after LVAD implantation. This is an important and poorly-understood aspect of LVAD therapy, because several studies have shown strong inter and intrapatient thrombogenic variability and current LVAD implantation strategies do not incorporate outflow graft angle optimization. Accurate platelet-level investigation, enabled by statistical treatment of outliers in Lagrangian particle tracking, demonstrates a strong influence of outflow graft anastomoses angle on thrombogenicity (platelet residence times and activation state characterized by shear stress accumulation) with significantly reduced TP for acutely-angled anastomosed outflow grafts. The methodology presented in this study provides a device-neutral platform for conducting comprehensive thrombogenicity evaluation of LVAD surgical configurations, empowering optimal patient-focused surgical strategies for long-term treatment and care for advanced heart failure patients.

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.

A modification of Murray's law for shear-thinning rheology.

This study reformulates Murray's well-known principle of minimum work as applied to the cardiovascular system to include the effects of the shear-thinning rheology of blood. The viscous behavior is described using the extended modified power law (EMPL), which is a time-independent, but shear-thinning rheological constitutive equation. The resulting minimization problem is solved numerically for typical parameter ranges. The non-Newtonian analysis still predicts the classical cubic diameter dependence of the volume flow rate and the cubic branching law. The current analysis also predicts a constant wall shear stress throughout the vascular tree, albeit with a numerical value about 15-25% higher than the Newtonian analysis. Thus, experimentally observed deviations from the cubic branching law or the predicted constant wall shear stress in the vasculature cannot likely be attributed to blood's shear-thinning behavior. Further differences between the predictions of the non-Newtonian and the Newtonian analyses are highlighted, and the limitations of the Newtonian analysis are discussed. Finally, the range and limits of applicability of the current results as applied to the human arterial tree are also discussed.

Leakage of central venous catheter locking fluid by hemodynamic transport.

Central venous catheters are often filled when not in use with an anticoagulating fluid, usually heparinized saline, known as the locking fluid. However, the use of the locking fluid is associated with known risks because of "leakage" of the lock. A new hypothesis is proposed here to explain the lock fluid leakage: that the leakage is due to advective and diffusive mass transfer by blood flow around the catheter tip in situ. On the basis of previous in vitro experiments, the leakage mechanism has been hypothesized to be fluid motion driven by buoyancy forces between the heavier blood and the lighter locking fluid. The current hypothesis is justified by a simple one-dimensional mass transfer model and more sophisticated three-dimensional computational hemodynamic simulations of an idealized catheter. The results predict an initial, fast (<10 seconds) advection-dominated phase, which may deplete up to 10% of the initial lock, followed by a slow diffusion-limited phase which predicts an additional 1-2% of leakage during a 48 hour period. The current results predict leakage rates that are more consistent with published in vivo data when compared with the buoyancy hypothesis predictions, which tend to grossly overestimate leakage rates.

Effects of wall distensibility in hemodynamic simulations of an arteriovenous fistula.

Arteriovenous fistulae are created surgically to provide adequate access for dialysis patients suffering from end-stage renal disease. It has long been hypothesized that the rapid blood vessel remodeling occurring after fistula creation is in part a process to restore the mechanical stresses to some preferred level, i.e., mechanical homeostasis. The current study presents fluid-structure interaction (FSI) simulations of a patient-specific model of a mature arteriovenous fistula reconstructed from 3D ultrasound scans. The FSI results are compared with previously published data of the same model but with rigid walls. Ultrasound-derived wall motion measurements are also used to validate the FSI simulations of the wall motion. Very large time-averaged shear stresses, 10-15 Pa, are calculated at the fistula anastomosis in the FSI simulations, values which are much larger than what is typically thought to be the normal homeostatic shear stress in the peripheral vasculature. Although this result is systematically lower by as much as 50% compared to the analogous rigid-walled simulations, the inclusion of distensible vessel walls in hemodynamic simulations does not reduce the high anastomotic shear stresses to "normal" values. Therefore, rigid-walled analyses may be acceptable for identifying high shear regions of arteriovenous fistulae.

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.

Incomplete restoration of homeostatic shear stress within arteriovenous fistulae.

Arteriovenous fistulae are surgically created to provide adequate access for dialysis patients suffering from end-stage renal disease. It has long been hypothesized that the rapid blood vessel remodeling occurring after fistula creation is, in part, a process to restore the mechanical stresses to some preferred level, i.e., mechanical homeostasis. We present computational hemodynamic simulations in four patient-specific models of mature arteriovenous fistulae reconstructed from 3D ultrasound scans. Our results suggest that these mature fistulae have remodeled to return to ''normal'' shear stresses away from the anastomoses: about 1.0 Pa in the outflow veins and about 2.5 Pa in the inflow arteries. Large parts of the anastomoses were found to be under very high shear stresses >15 Pa, over most of the cardiac cycle. These results suggest that the remodeling process works toward restoring mechanical homeostasis in the fistulae, but that the process is limited or incomplete, even in mature fistulae, as evidenced by the elevated shear at or near the anastomoses. Based on the long term clinical viability of these dialysis accesses, we hypothesize that the elevated nonhomeostatic shear stresses in some portions of the vessels were not detrimental to fistula patency.

Hemodynamic conditions in a failing peripheral artery bypass graft.

OBJECTIVE: The mechanisms of restenosis in autogenous vein bypass grafts placed for peripheral artery disease are not completely understood. We investigated the role of hemodynamic stress in a case study of a revised bypass graft that failed due to restenosis. METHODS: The morphology of the lumen was reconstructed from a custom three-dimensional ultrasound system. Scans were taken at 1, 6, and 16 months after a patch angioplasty procedure. Computational hemodynamic simulations of the patient-specific model provided the blood flow features and the hemodynamic stresses on the vessel wall at the three times studied. RESULTS: The vessel was initially free of any detectable lesions, but a 60% diameter-reducing stenosis developed during the 16-month study interval. As determined from the simulations, chaotic and recirculating flow occurred downstream of the stenosis due to the sudden widening of the lumen at the patch location. Curvature and a sudden increase in the lumen cross-sectional area induced these flow features that are hypothesized to be conducive to intimal hyperplasia. Favorable agreement was found between simulation results and in vivo Doppler ultrasound velocity measurements. CONCLUSIONS: Transitional and chaotic flow occurs at the site of the revision, inducing a complex pattern of wall shear as computed with the hemodynamic simulations. This supports the hypothesis that the hemodynamic stresses in the revised segment, produced by the coupling of vessel geometry and chaotic flow, led to the intimal hyperplasia and restenosis of the graft.

A longitudinal study of remodeling in a revised peripheral artery bypass graft using 3D ultrasound imaging and computational hemodynamics.

We report a study of the role of hemodynamic shear stress in the remodeling and failure of a peripheral artery bypass graft. Three separate scans of a femoral to popliteal above-knee bypass graft were taken over the course of a 16 month period following a revision of the graft. The morphology of the lumen is reconstructed from data obtained by a custom 3D ultrasound system. Numerical simulations are performed with the patient-specific geometries and physiologically realistic flow rates. The ultrasound reconstructions reveal two significant areas of remodeling: a stenosis with over 85% reduction in area, which ultimately caused graft failure, and a poststenotic dilatation or widening of the lumen. Likewise, the simulations reveal a complicated hemodynamic environment within the graft. Preliminary comparisons with in vivo velocimetry also showed qualitative agreement with the flow dynamics observed in the simulations. Two distinct flow features are discerned and are hypothesized to directly initiate the observed in vivo remodeling. First, a flow separation occurs at the stenosis. A low shear recirculation region subsequently develops distal to the stenosis. The low shear region is thought to be conducive to smooth muscle cell proliferation and intimal growth. A poststenotic jet issues from the stenosis and subsequently impinges onto the lumen wall. The lumen dilation is thought to be a direct result of the high shear stress and high frequency pressure fluctuations associated with the jet impingement.