Stimulated by a recent controversy regarding pressure drops predicted in a giant aneurysm with a proximal stenosis, the present study sought to assess variability in the prediction of pressures and flow by a wide variety of research groups. In phase I, lumen geometry, flow rates, and fluid properties were specified, leaving each research group to choose their solver, discretization, and solution strategies. Variability was assessed by having each group interpolate their results onto a standardized mesh and centerline. For phase II, a physical model of the geometry was constructed, from which pressure and flow rates were measured. Groups repeated their simulations using a geometry reconstructed from a micro-computed tomography (CT) scan of the physical model with the measured flow rates and fluid properties. Phase I results from 25 groups demonstrated remarkable consistency in the pressure patterns, with the majority predicting peak systolic pressure drops within 8% of each other. Aneurysm sac flow patterns were more variable with only a few groups reporting peak systolic flow instabilities owing to their use of high temporal resolutions. Variability for phase II was comparable, and the median predicted pressure drops were within a few millimeters of mercury of the measured values but only after accounting for submillimeter errors in the reconstruction of the life-sized flow model from micro-CT. In summary, pressure can be predicted with consistency by CFD across a wide range of solvers and solution strategies, but this may not hold true for specific flow patterns or derived quantities. Future challenges are needed and should focus on hemodynamic quantities thought to be of clinical interest.

Embolus Analogues (EAs) can provide understanding of the mechanical characteristics of blood clots of cardiac origin. Bovine EAs (n = 29) were fabricated with varying concentrations of thrombin (0-20 NIHU/ml blood). Histological staining confirmed that EA composition compared sufficiently with human samples reported in literature. EAs were mechanically described under seven testing conditions: tensile, compression, shear wave ultrasound elastography (SWE), parallel plate rheometry, indentation, creep and relaxation. The Young modulus of bovine EAs in tension varied from 7 kPa (5% strain) to 84 kPa (50% strain). The compressive Young modulus increased with increasing thrombin concentration, which was in agreement with the SWE results. There was no significant difference in Young modulus throughout the clot (p < 0.05). The EAs displayed a non-linear response under parallel plate rheometry, creep and stress relaxation. The 3rd order Mooney-Rivlin constitutive equation and Standard Linear Solid model were used to fit the non-linear stress-strain response and time-dependent properties, respectively. This is the first study in which bovine EAs, with and without addition of thrombin, are histologically and mechanically described with corresponding proposed constitutive equations. The equations and experimental data determined can be applied for future numerical and experimental testing of mammalian EAs and cardiac source clots.

A complete circle of Willis (CoW) is found in approximately 30-50% of the population. Anatomical variations, such as absent or surgically clamped vessels, can result in undesirable flow patterns. These can affect the brain's ability to maintain cerebral perfusion and the formation of cerebral aneurysms. An experimental test system was developed to simulate cerebral physiological conditions through three flexible 3D patient-specific models of complete and incomplete CoW geometries. Flow visualizations were performed with isobaric dyes and the mapped dye streamlines were tracked throughout the models. Three to seven flow impact locations were observed for all configurations, corresponding to known sites for aneurysmal formation. Uni and bi-directional cross-flows occurred along the communicating arteries. The greatest shunting of flow occurred for a missing pre-communicating anterior (A1) and posterior (P1) cerebral arteries. The anterior cerebral arteries had the greatest reduction (15-37%) in efferent flow rates for missing either a unilateral A1 or bilateral P1 segments. The bi-directional cross-flows, with multiple afferent flow mixing, observed along the communicating arteries may explain the propensity of aneurysm formation at these sites. Reductions in efferent flow rates due to aplastic vessel configurations may affect normal brain function.

In vitro simulations of the trajectory and lodgement locations of emboli within the circle of Willis (CoW) are crucial in understanding the associated hemodynamic effects in stroke patients. A clot was fabricated from the hemolymph of a crustacean species. Clots were injected into the internal carotid artery via a cerebral flow facility housing a manufactured CoW human model. The trajectory of the clot was tracked and its hemodynamic effects monitored. The clots traveled with an average velocity of 88 mm/s along the ipsilateral side with momentary pauses along high curvature regions before finally lodging within the distal branches of the ipsilateral middle cerebral artery (MCA). These clots either elongated along the branching vessels or compressed against a bifurcation point. A blocked M1-segment of the MCA reduced the efferent blood pressure and flow rates by (15-77%) and (20-100%) respectively with a re-distribution of the flow towards the other efferent vessels. Mimicking blood clots with crustacean hemolymph provides a much lower biohazard risk than using human or mammalian blood clots and a superior alternative to synthetic materials. The geometry of the distal MCA vasculature will determine the end morphology of the lodged clot. Clotting severely reduces the distal flow rates and pressures.

Haematological malignancies are a large collection of heterogeneous blood cancers with huge variation in presentation, treatment and prognosis, ranging from acute leukaemias, high-grade lymphoma and aggressive multiple myeloma to more indolent neoplasms such as low-grade lymphomas and myelodysplastic syndromes (Ruiz et al., 2018). Intensive chemotherapy is used in the management of many haematological cancers, and this can result in severe and debilitating adverse events (Button, Bolton, et al., 2019a). Patients with

The Circle of Willis (CoW) is a complex pentagonal network comprised of fourteen cerebral vessels located at the base of the brain. The collateral flow feature within the circle of Willis allows the ability to maintain cerebral perfusion of the brain. Unfortunately, this collateral flow feature can create undesirable flow impact locations due to anatomical variations within the CoW. The interaction between hemodynamic forces and the arterial wall are believed to be involved in the formation of cerebral aneurysms, especially at irregular geometries such as tortuous segments, bends, and bifurcations. The highest propensity of aneurysm formation is known to form at the anterior communicating artery (AcoA) and at the junctions of the internal carotid and posterior communicating arteries (PcoAs). Controversy still remains as to the existence of blood flow paths through the communicating arteries for a normal CoW. This paper experimentally describes the hemodynamic conditions through three thin walled patient specific models of a complete CoW based on medical images. These models were manufactured by a horizontal dip spin coating method and positioned within a custom made cerebral testing system that simulated symmetrical physiological afferent flow conditions through the internal carotid and vertebral arteries. The dip spin coating procedure produced excellent dimensional accuracy. There was an average of less than 4% variation in diameters and wall thicknesses throughout all manufactured CoW models. Our cerebral test facility demonstrated excellent cycle to cycle repeatability, with variations of less than 2% and 1% for the time and cycle averaged flow rates, respectively. The peak systolic flow rates had less than a 4% variation. Our flow visualizations showed four independent flow sources originating from all four inlet arteries impacting at and crossing the AcoA with bidirectional cross flows. The flow paths entering the left and right vertebral arteries dissipated throughout the CoW vasculature from the posterior to anterior sides, exiting through all efferent vessels. Two of the models had five flow impact locations, while the third model had an additional two impact locations within the posterior circulation caused by an additional bidirectional cross flows along the PcoAs during the accelerating and part of the decelerating phases. For a complete CoW, bidirectional cross flows exist within the AcoA and geometrical variations within the CoW geometry can either promote uni- or bidirectional cross flows along the PcoAs.

The coronary arterial tree experiences large displacements due to the contraction and expansion of the cardiac muscle and may influence coronary haemodynamics and stent placement. The accurate measurement of catheter trackability forces within physiological relevant test systems is required for optimum catheter design. The effects of cardiac motion on coronary flowrates, pressure drops, and stent delivery has not been previously experimentally assessed. A cardiac simulator was designed and manufactured which replicates physiological coronary flowrates and cardiac motion within a patient-specific geometry. A motorized delivery system delivered a commercially available coronary stent system and monitored the trackability forces along three phantom patient-specific thin walled compliant coronary vessels supported by a dynamic cardiac phantom model. Pressure drop variation is more sensitive to cardiac motion than outlet flowrates. Maximum pressure drops varied from 7 to 49 mmHg for a stenosis % area reduction of 56 to 90%. There was a strong positive linear correlation of cumulative trackability force with the cumulative curvature. The maximum trackability forces and curvature ranged from 0.24 to 0.87 N and 0.06 to 0.22 mm(-1) respectively for all three vessels. There were maximum and average percentage differences in trackability forces of (23-49%) and (1.9-5.2%) respectively when comparing a static pressure case with the inclusion of pulsatile flow and cardiac motion. Cardiac motion with pulsatile flow significantly altered (p value <0.001) the trackability forces along the delivery pathways with high local percentage variations and pressure drop measurements.

The circle of Willis (CoW) is a complex arterial network comprising of major cerebral arteries that converge to form a pentagonal arrangement as shown in Figure 1(A). This arterial network supplies oxygen-enriched blood to the brain. An incomplete CoW can exist in up to 50% of cases [1]. These missing vessels can be accommodated by the collateral flow feature within the CoW configuration. In certain circumstances, anatomical variations within the CoW can result in undesirable flow patterns [2–3]. It is unclear from the literature what effects these variations can have on blood flow collision paths within a complete CoW.