Extended finite element method for fluid-structure interaction in wave membrane blood pump.

Numerical simulations of cardiac blood pump systems are integral to the optimization of device design, hydraulic performance and hemocompatibility. In wave membrane blood pumps, blood propulsion arises from the wave propagation along an oscillating immersed membrane, which generates small pockets of fluid that are pushed towards the outlet against an adverse pressure gradient. We studied the Fluid-Structure Interaction between the oscillating membrane and the blood flow via three-dimensional simulations using the Extended Finite Element Method (XFEM), an unfitted numerical technique that avoids remeshing by using a fluid fixed mesh. Our three-dimensional numerical simulations in a realistic pump geometry highlighted, for the first time in this field of application, that XFEM is a reliable strategy to handle complex industrial problems. Moreover, they showed the role of the membrane deformation in promoting a blood flow towards the outlet despite an adverse pressure gradient. We also simulated the pump system at different pressure conditions and we validated the numerical results against in-vitro experimental data.

Space and Time Resolved Detection of Platelet Activation and von Willebrand Factor Conformational Changes in Deep Suspensions.

Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in in vitro replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and the percentage of activated platelets determined through flow cytometry is obtained, validating the technique. An increase in the number of rVWF-eGFP signals upon exposure to shear stress demonstrates the technique's ability to detect breakup of self-aggregates. VWF globular and unfolded conformations and self-aggregation are also observed. The ability to track the size and shape of VWF-platelet strands in space and time provides means to detect pro- and antithrombotic processes.

Intracorporeal Heat Distribution from Fully Implantable Energy Sources for Mechanical Circulatory Support: A Computational Proof-of-Concept Study.

Mechanical circulatory support devices, such as total artificial hearts and left ventricular assist devices, rely on external energy sources for their continuous operation. Clinically approved power supplies rely on percutaneous cables connecting an external energy source to the implanted device with the associated risk of infections. One alternative, investigated in the 70s and 80s, employs a fully implanted nuclear power source. The heat generated by the nuclear decay can be converted into electricity to power circulatory support devices. Due to the low conversion efficiencies, substantial levels of waste heat are generated and must be dissipated to avoid tissue damage, heat stroke, and death. The present work computationally evaluates the ability of the blood flow in the descending aorta to remove the locally generated waste heat for subsequent full-body distribution and dissipation, with the specific aim of investigating methods for containment of local peak temperatures within physiologically acceptable limits. To this aim, coupled fluid-solid heat transfer computational models of the blood flow in the human aorta and different heat exchanger architectures are developed. Particle tracking is used to evaluate temperature histories of cells passing through the heat exchanger region. The use of the blood flow in the descending aorta as a heat sink proves to be a viable approach for the removal of waste heat loads. With the basic heat exchanger design, blood thermal boundary layer temperatures exceed 50°C, possibly damaging blood cells and proteins. Improved designs of the heat exchanger, with the addition of fins and heat guides, allow for drastically lower blood temperatures, possibly leading to a more biocompatible implant. The ability to maintain blood temperatures at biologically compatible levels will ultimately allow for the body-wise distribution, and subsequent dissipation, of heat loads with minimum effects on the human physiology.

Biomechanical changes during abdominal aortic aneurysm growth.

The biomechanics-based Abdominal Aortic Aneurysm (AAA) rupture risk assessment has gained considerable scientific and clinical momentum. However, such studies have mainly focused on information at a single time point, and little is known about how AAA properties change over time. Consequently, the present study explored how geometry, wall stress-related and blood flow-related biomechanical properties change during AAA expansion. Four patients with a total of 23 Computed Tomography-Angiography (CT-A) scans at different time points were analyzed. At each time point, patient-specific properties were extracted from (i) the reconstructed geometry, (ii) the computed wall stress at Mean Arterial Pressure (MAP), and (iii) the computed blood flow velocity at standardized inflow and outflow conditions. Testing correlations between these parameters identified several nonintuitive dependencies. Most interestingly, the Peak Wall Rupture Index (PWRI) and the maximum Wall Shear Stress (WSS) independently predicted AAA volume growth. Similarly, Intra-luminal Thrombus (ILT) volume growth depended on both the maximum WSS and the ILT volume itself. In addition, ILT volume, ILT volume growth, and maximum ILT layer thickness correlated with PWRI as well as AAA volume growth. Consequently, a large ILT volume as well as fast increase of ILT volume over time may be a risk factor for AAA rupture. However, tailored clinical studies would be required to test this hypothesis and to clarify whether monitoring ILT development has any clinical benefit.

Synergy between shear-induced migration and secondary flows on red blood cells transport in arteries: considerations on oxygen transport.

Shear-induced migration of red blood cells (RBCs) is a well-known phenomenon characterizing blood flow in the small vessels (micrometre to millimetre size) of the cardiovascular system. In large vessels, like the abdominal aorta and the carotid artery (millimetre to centimetre size), the extent of this migration and its interaction with secondary flows has not been fully elucidated. RBC migration exerts its influence primarily on platelet concentration, oxygen transport and oxygen availability at the luminal surface, which could influence vessel wall disease processes in and adjacent to the intima. Phillips' shear-induced particle migration model, coupled to the Quemada viscosity model, was employed to simulate the macroscopic behaviour of RBCs in four patient-specific geometries: a normal abdominal aorta, an abdominal aortic aneurysm (AAA), a normal carotid bifurcation and a stenotic carotid bifurcation. Simulations show a migration of RBCs from the near-wall region with a lowering of wall haematocrit (volume fraction of RBCs) on the posterior side of the normal aorta and on the lateral-external side of the iliac arteries. A marked migration is observed on the outer wall of the carotid sinus, along the common carotid artery and in the carotid stenosis. No significant migration is observed in the AAA. The spatial and temporal patterns of wall haematocrit are correlated with the near-wall shear layer and with the secondary flows induced by the vessel curvature. In particular, secondary flows accentuate the initial lowering in RBC near-wall concentration by convecting RBCs from the inner curvature side to the outer curvature side. The results reinforce data in literature showing a decrease in oxygen partial pressure on the inner curvature wall of the carotid sinus induced by the presence of secondary flows. The lowering of wall haematocrit is postulated to induce a decrease in oxygen availability at the luminal surface through a diminished concentration of oxyhaemoglobin, hence contributing, with the reported lowered oxygen partial pressure, to local hypoxia.

An integrated fluid-chemical model toward modeling the formation of intra-luminal thrombus in abdominal aortic aneurysms.

Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development.

Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation.

Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

Hemodynamics of the normal aorta compared to fusiform and saccular abdominal aortic aneurysms with emphasis on a potential thrombus formation mechanism.

Abdominal Aortic Aneurysms (AAAs), i.e., focal enlargements of the aorta in the abdomen are frequently observed in the elderly population and their rupture is highly mortal. An intra-luminal thrombus is found in nearly all aneurysms of clinically relevant size and multiply affects the underlying wall. However, from a biomechanical perspective thrombus development and its relation to aneurysm rupture is still not clearly understood. In order to explore the impact of blood flow on thrombus development, normal aortas (n = 4), fusiform AAAs (n = 3), and saccular AAAs (n = 2) were compared on the basis of unsteady Computational Fluid Dynamics simulations. To this end patient-specific luminal geometries were segmented from Computerized Tomography Angiography data and five full heart cycles using physiologically realistic boundary conditions were analyzed. Simulations were carried out with computational grids of about half a million finite volume elements and the Carreau-Yasuda model captured the non-Newtonian behavior of blood. In contrast to the normal aorta the flow in aneurysm was highly disturbed and, particularly right after the neck, flow separation involving regions of high streaming velocities and high shear stresses were observed. Naturally, at the expanded sites of the aneurysm average flow velocity and wall shear stress were much lower compared to normal aortas. These findings suggest platelets activation right after the neck, i.e., within zones of pronounced recirculation, and platelet adhesion, i.e., thrombus formation, downstream. This mechanism is supported by recirculation zones promoting the advection of activated platelets to the wall.