Patrick M. McGah

Cerebral Aneurysms Treated with Flow-Diverting Stents: Computational Models with Intravascular Blood Flow Measurements

BACKGROUND AND PURPOSE: Computational fluid dynamics modeling is useful in the study of the hemodynamic environment of cerebral aneurysms, but patient-specific measurements of boundary conditions, such as blood flow velocity and pressure, have not been previously applied to the study of flow-diverting stents. We integrated patient-specific intravascular blood flow velocity and pressure measurements into computational models of aneurysms before and after treatment with flow-diverting stents to determine stent effects on aneurysm hemodynamics. MATERIALS AND METHODS: Blood flow velocity and pressure were measured in peri-aneurysmal locations by use of an intravascular dual-sensor pressure and Doppler velocity guidewire before and after flow-diverting stent treatment of 4 unruptured cerebral aneurysms. These measurements defined inflow and outflow boundary conditions for computational models. Intra-aneurysmal flow rates, wall shear stress, and wall shear stress gradient were calculated. RESULTS: Measurements of inflow velocity and outflow pressure were successful in all 4 patients. Computational models incorporating these measurements demonstrated significant reductions in intra-aneurysmal wall shear stress and wall shear stress gradient and a trend in reduced intra-aneurysmal blood flow. CONCLUSIONS: Integration of intravascular dual-sensor guidewire measurements of blood flow velocity and blood pressure provided patient-specific computational models of cerebral aneurysms. Aneurysm treatment with flow-diverting stents reduces blood flow and hemodynamic shear stress in the aneurysm dome.

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.

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.

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.

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.

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 Modeling of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension

BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension has been associated with dural venous sinus stenosis in some patients, but the hemodynamic environment of the dural venous sinuses has not been quantitatively described. Here, we present the first such computational fluid dynamics model by using patient-specific blood pressure measurements. MATERIALS AND METHODS: Six patients with idiopathic intracranial hypertension and at least 1 stenosis or atresia at the transverse/sigmoid sinus junction underwent MR venography followed by cerebral venography and manometry throughout the dural venous sinuses. Patient-specific computational fluid dynamics models were created by using MR venography anatomy, with venous pressure measurements as boundary conditions. Blood flow and wall shear stress were calculated for each patient. RESULTS: Computational models of the dural venous sinuses were successfully reconstructed in all 6 patients with patient-specific boundary conditions. Three patients demonstrated a pathologic pressure gradient (≥8 mm Hg) across 4 dural venous sinus stenoses. Small sample size precludes statistical comparisons, but average overall flow throughout the dural venous sinuses of patients with pathologic pressure gradients was higher than in those without them (1041.00 ± 506.52 mL/min versus 358.00 ± 190.95 mL/min). Wall shear stress was also higher across stenoses in patients with pathologic pressure gradients (37.66 ± 48.39 Pa versus 7.02 ± 13.60 Pa). CONCLUSIONS: The hemodynamic environment of the dural venous sinuses can be computationally modeled by using patient-specific anatomy and physiologic measurements in patients with idiopathic intracranial hypertension. There was substantially higher blood flow and wall shear stress in patients with pathologic pressure gradients.

In vitro validation of endovascular Doppler-derived flow rates in models of the cerebral circulation

This study presents validation of endovascular Doppler velocimetry-based volumetric flow rate measurements conducted in a pulsatile flow loop simulating conditions in both the internal carotid and basilar artery. In vitro models of cerebral vessels, each containing an aneurysm, were fabricated from patient anatomies extracted from 3D rotational angiography. Flow velocity measurements were collected with three different experimental techniques: an endovascular Doppler wire, Particle Image Velocimetry, and a time-resolved ultrasonic flow meter. Womersleys theory of pulsatile flow in a cylindrical vessel was used to compute time-resolved volumetric flow rates from the endovascular Doppler velocity. The volumetric flow rates computed from the Doppler measurements were compared to those from the Particle Image Velocimetry profile measurements, and the direct measurements from the ultrasonic flow meter. The study establishes confidence intervals for any systematic or random errors associated with the wire-derived flow rates as benchmarked to the other two modalities. There is an approximately 10% random error in the Doppler-derived peak and time-averaged flow rates. There is a measurable uniform bias, about 15% too low, in the time-averaged Doppler-derived flow rates. There is also a small proportional bias in the peak systolic Doppler-derived flow rates. Potential sources of error 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.