Mathematical modeling of thrombus formation in idealized models of aortic dissection: Initial findings and potential applications

Aortic dissection is a major aortic catastrophe with a high morbidity and mortality risk caused by the formation of a tear in the aortic wall. The development of a second blood filled region defined as the “false lumen” causes highly disturbed flow patterns and creates local hemodynamic conditions likely to promote the formation of thrombus in the false lumen. Previous research has shown that patient prognosis is influenced by the level of thrombosis in the false lumen, with false lumen patency and partial thrombosis being associated with late complications and complete thrombosis of the false lumen having beneficial effects on patient outcomes. In this paper, a new hemodynamics-based model is proposed to predict the formation of thrombus in Type B dissection. Shear rates, fluid residence time, and platelet distribution are employed to evaluate the likelihood for thrombosis and to simulate the growth of thrombus and its effects on blood flow over time. The model is applied to different idealized aortic dissections to investigate the effect of geometric features on thrombus formation. Our results are in qualitative agreement with in-vivo observations, and show the potential applicability of such a modeling approach to predict the progression of aortic dissection in anatomically realistic geometries

Effect of a Flared Renal Stent on the Performance of Fenestrated Stent-Grafts at Rest and Exercise Conditions

Purpose: To quantify the hemodynamic impact of a flared renal stent on the performance of fenestrated stent-grafts (FSGs) by analyzing flow patterns and wall shear stress–derived parameters in flared and nonflared FSGs in different physiologic scenarios. Methods: Hypothetical models of FSGs were created with and without flaring of the proximal portion of the renal stent. Flared FSGs with different dilation angles and protrusion lengths were examined, as well as a nonplanar flared FSG to account for lumbar curvature. Laminar and pulsatile blood flow was simulated by numerically solving Navier-Stokes equations. A physiologically realistic flow rate waveform was prescribed at the inlet, while downstream vasculature was modeled using a lumped parameter 3-element windkessel model. No slip boundary conditions were imposed at the FSG walls, which were assumed to be rigid. While resting simulations were performed on all the FSGs, exercise simulations were also performed on a flared FSG to quantify the effect of flaring in different physiologic scenarios. Results: For cycle-averaged inflow of 2.94 L/min (rest) and 4.63 L/min (exercise), 27% of blood flow was channeled into each renal branch at rest and 21% under exercise for all the flared FSGs examined. Although the renal flow waveform was not affected by flaring, flow within the flared FSGs was disturbed. This flow disturbance led to high endothelial cell activation potential (ECAP) values at the renal ostia for all the flared geometries. Reducing the dilation angle or protrusion length and exercise lowered the ECAP values for flared FSGs. Conclusion: Flaring of renal stents has a negligible effect on the time dependence of renal flow rate waveforms and can maintain sufficient renal perfusion at rest and exercise. Local flow patterns are, however, strongly dependent on renal flaring, which creates a local flow disturbance and may increase the thrombogenicity at the renal ostia. Smaller dilation angles, shorter protrusion lengths, and moderate lower limb exercise are likely to reduce the risk of thrombosis in flared geometries

Towards a multi-physics modelling framework for thrombolysis under the influence of blood flow

Thrombolytic therapy is an effective means of treating thromboembolic diseases but can also give rise to life-threatening side-effects. The infusion of a high drug concentration can provoke internal bleeding while an insufficient dose can lead to artery reocclusion. It is hoped that mathematical modelling of the process of clot lysis can lead to a better understanding and improvement of thrombolytic therapy. To this end, a multi-physics continuum model has been developed to simulate the dissolution of clot over time upon the addition of tissue plasminogen activator (tPA). The transport of tPA and other lytic proteins is modelled by a set of reaction-diffusion-convection equations, while blood flow is described by volume-averaged continuity and momentum equations. The clot is modelled as a fibrous porous medium with its properties being determined as a function of the fibrin fibre radius and voidage of the clot. A unique feature of the model is that it is capable of simulating the entire lytic process from the initial phase of lysis of an occlusive thrombus (diffusion-limited transport), the process of recanalization, to post-canalization thrombolysis under the influence of convective blood flow. The model has been used to examine the dissolution of a fully occluding clot in a simplified artery at different pressure drops. Our predicted lytic front velocities during the initial stage of lysis agree well with experimental and computational results reported by others. Following canalisation, clot lysis patterns are strongly influenced by local flow patterns which are symmetric at low pressure drops, but asymmetric at higher pressure drops which give rise to larger recirculation regions and extended areas of intense drug accumulation

Hemodynamic evaluation using four-dimensional flow magnetic resonance imaging for a patient with multichanneled aortic dissection

The hemodynamic function of multichanneled aortic dissection (MCAD) requires close monitoring and effective management to avoid potentially catastrophic sequelae. This report describes a 47-year-old man who underwent endovascular repair based on findings from four-dimensional (4D) flow magnetic resonance imaging of an MCAD. The acquired 4D flow data revealed complex, bidirectional flow patterns in the false lumens and accelerated blood flow in the compressed true lumen. The collapsed abdominal true lumen expanded unsatisfactorily after primary tear repair, which required further remodeling with bare stents. This case study demonstrates that hemodynamic analysis using 4D flow magnetic resonance imaging can help understand the complex pathologic changes of MCAD

Comparison of blood flow in branched and fenestrated stent-grafts for endovascular repair of abdominal aortic aneurysms.

Purpose: To report a computational study assessing the hemodynamic outcomes of branched stent-grafts (BSGs) for different anatomic variations. Methods: Idealized models of BSGs and fenestrated stent-grafts (FSGs) were constructed with different visceral takeoff angles (ToA) and lateral aortic neck angles. ToA was defined as the angle between the centerlines of the main stent-graft and side branch, with 90° representing normal alignment, and 30° and 120° representing angulated side branches. Computational simulations were performed by solving the conservation equations governing the blood flow under physiologically realistic conditions. Results: The largest renal flow recirculation zones (FRZs) were observed in FSGs at a ToA of 30°, and the smallest FRZ was also found in FSGs (at a ToA of 120°). For straight-neck stent-grafts with a ToA of 90°, mean flow in each renal artery was 0.54, 0.46, and 0.62 L/min in antegrade BSGs, retrograde BSGs, and FSGs, respectively. For angulated stent-grafts, the corresponding values were 0.53, 0.48, and 0.63 L/min. All straight-neck stent-grafts experienced equal cycle-averaged displacement forces of 1.25, 1.69, and 1.95 N at ToAs of 30°, 90°, and 120°, respectively. Angulated main stent-grafts experienced an equal cycle-averaged displacement force of 3.6 N. Conclusion: The blood flow rate in renal arteries depends on the configuration of the stent-graft, with an FSG giving maximum renal flow and a retrograde BSG resulting in minimum renal flow. Nevertheless, the difference was small, up to 0.09 L/min. Displacement forces exerted on stent-grafts are very sensitive to lateral neck angle but not on the configuration of the stent-graft

Hemodynamic Functions of Fenestrated Stent Graft under Resting, Hypertension, and Exercise Conditions.

The aim of this study was to assess the hemodynamic performance of a patient-specific fenestrated stent graft (FSG) under different physiological conditions, including normal resting, hypertension, and hypertension with moderate lower limb exercise. A patient-specific FSG model was constructed from computed tomography images and was discretized into a fine unstructured mesh comprising tetrahedral and prism elements. Blood flow was simulated using Navier-Stokes equations, and physiologically realistic boundary conditions were utilized to yield clinically relevant results. For a given cycle-averaged inflow of 2.08 L/min at normal resting and hypertension conditions, approximately 25% of flow was channeled into each renal artery. When hypertension was combined with exercise, the cycle-averaged inflow increased to 6.39 L/min but only 6.29% of this was channeled into each renal artery, which led to a 438.46% increase in the iliac flow. For all the simulated scenarios and throughout the cardiac cycle, the instantaneous flow streamlines in the FSG were well organized without any notable flow recirculation. This well-organized flow led to low values of endothelial cell activation potential, which is a hemodynamic metric used to identify regions at risk of thrombosis. The displacement forces acting on the FSG varied with the physiological conditions, and the cycle-averaged displacement force at normal rest, hypertension, and hypertension with exercise was 6.46, 8.77, and 8.99 N, respectively. The numerical results from this study suggest that the analyzed FSG can maintain sufficient blood perfusion to the end organs at all the simulated conditions. Even though the FSG was found to have a low risk of thrombosis at rest and hypertension, this risk can be reduced even further with moderate lower limb exercise