Aortic valve neocuspidization and bioprosthetic valves: Evaluating turbulence haemodynamics.

Aortic valve disease is often treated with bioprosthetic valves. An alternative treatment is aortic valve neocuspidization which is a relatively new reparative procedure whereby the three aortic cusps are replaced with patient pericardium or bovine tissues. Recent research indicates that aortic blood flow is disturbed, and turbulence effects have yet to be evaluated in either bioprosthetic or aortic valve neocuspidization valve types in patient-specific settings. The aim of this study is to better understand turbulence production in the aorta and evaluate its effects on laminar and turbulent wall shear stress. Four patients with aortic valve disease were treated with either bioprosthetic valves (n=2) or aortic valve neocuspidization valvular repair (n=2). Aortic geometries were segmented from magnetic resonance images (MRI), and 4D flow MRI was used to derive physiological inlet and outlet boundary conditions. Pulsatile large-eddy simulations were performed to capture the full range of laminar, transitional and turbulence characteristics in the aorta. Turbulence was produced in all aortas with highest levels occurring during systolic deceleration. In the ascending aorta, turbulence production is attributed to a combination of valvular skew, valvular eccentricity, and ascending aortic dilation. In the proximal descending thoracic aorta, turbulence production is dependent on the type of arch-descending aorta connection (e.g., a narrowing or sharp bend) which induces flow separation. Laminar and turbulent wall shear stresses are of similar magnitude throughout late systolic deceleration and diastole, although turbulent wall shear stress magnitudes exceed laminar wall shear stresses between 27.3% and 61.1% of the cardiac cycle. This emphasises the significance of including turbulent wall shear stress to improve our comprehension of progressive arterial wall diseases. The findings of this study recommend that aortic valve treatments should prioritise minimising valvular eccentricity and skew in order to mitigate turbulence generation.

Evaluation of Computational Methodologies for Accurate Prediction of Wall Shear Stress and Turbulence Parameters in a Patient-Specific Aorta.

Background: Recent studies suggest that blood flow in main arteries is intrinsically disturbed, even under healthy conditions. Despite this, many computational fluid dynamics (CFD) analyses of aortic haemodynamics make the assumption of laminar flow, and best practices surrounding appropriate modelling choices are lacking. This study aims to address this gap by evaluating different modelling and post-processing approaches in simulations of a patient-specific aorta. Methods: Magnetic resonance imaging (MRI) and 4D flow MRI from a patient with aortic valve stenosis were used to reconstruct the aortic geometry and derive patient-specific inlet and outlet boundary conditions. Three different computational approaches were considered based on assumed laminar or assumed disturbed flow states including low-resolution laminar (LR-Laminar), high-resolution laminar (HR-Laminar) and large-eddy simulation (LES). Each simulation was ran for 30 cardiac cycles and post-processing was conducted on either the final cardiac cycle, or using a phase-averaged approach which utilised all 30 simulated cycles. Model capabilities were evaluated in terms of mean and turbulence-based parameters. Results: All simulation types, regardless of post-processing approach could correctly predict velocity values and flow patterns throughout the aorta. Lower resolution simulations could not accurately predict gradient-derived parameters including wall shear stress and viscous energy loss (largest differences up to 44.6% and 130.3%, respectively), although phase-averaging these parameters improved predictions. The HR-Laminar simulation produced more comparable results to LES with largest differences in wall shear stress and viscous energy loss parameters up to 5.1% and 11.6%, respectively. Laminar-based parameters were better estimated than turbulence-based parameters. Conclusion: Our findings suggest that well-resolved laminar simulations can accurately predict many laminar-based parameters in disturbed flows, but there is no clear benefit to running a HR-Laminar simulation over an LES simulation based on their comparable computational cost. Additionally, post-processing "typical" laminar simulation results with a phase-averaged approach is a simple and cost-effective way to improve accuracy of lower-resolution simulation results.

Multiphysics Modelling and Simulation of Thrombolysis via Activated Platelet-Targeted Nanomedicine.

PURPOSE: This study establishes a multiphysics simulation platform for both conventional and targeted thrombolysis using tissue plasminogen activator (tPA). Based on our computational results, the effects of therapeutic parameters on the dynamics of thrombolysis and the risk of side effects are investigated. METHODS: The model extends our previously developed one-dimensional(1D) mathematical models for fibrinolysis by incorporating targeted thrombolysis. It consists of two parts: (i) a coupled mathematical model of systemic pharmacokinetics (PK) and pharmacodynamics (PD) and local PD in a 1D occluded artery, and (ii) a mechanistic model for a targeted thrombolytic system via activated platelet-targeted tPA-loaded nanovesicles (tPA-NV), with model parameters derived from our in vitro experiments. A total of 16 therapeutic scenarios are simulated by varying the clot location and composition as well as the dosing regimen with free tPA or tPA-NV. RESULTS: Our simulation results indicate that tPA-NV offers several advantages over free tPA for thrombolysis. It reduces systemic exposure of tPA, thereby minimising the risk of bleeding complications. Simulations with different tPA-NV doses reveal that tPA-NV at 10% of the recommended dose can be as effective as the standard regimen with the full recommended dose of free tPA, demonstrating the potential of our tPA-NV as a new thrombolytic strategy with a reduced tPA dose. Moreover, faster recanalisation can be achieved with tPA-NV, especially for platelet-rich(or fibrin-poor) clots. CONCLUSIONS: Our simulation platform for thrombolysis with well-tuned model parameters can be used to evaluate and optimise treatment regimens of existing and new thrombolytic therapies via benefit/risk assessment under various therapeutic scenarios.

Modelling Combined Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischaemic Stroke: Understanding the Relationship between Stent Retriever Configuration and Clot Lysis Mechanisms.

Background: Combined intravenous thrombolysis and mechanical thrombectomy (IVT-MT) is a common treatment in acute ischaemic stroke, however the interaction between IVT and MT from a physiological standpoint is poorly understood. In this pilot study, we conduct numerical simulations of combined IVT-MT with various idealised stent retriever configurations to evaluate performance in terms of complete recanalisation times and lysis patterns. Methods: A 3D patient-specific geometry of a terminal internal carotid artery with anterior and middle cerebral arteries is reconstructed, and a thrombus is artificially implanted in the MCA branch. Various idealised stent retriever configurations are implemented by varying stent diameter and stent placement, and a configuration without a stent retriever provides a baseline for comparison. A previously validated multi-level model of thrombolysis is used, which incorporates blood flow, drug transport, and fibrinolytic reactions within a fibrin thrombus. Results: Fastest total recanalisation was achieved in the thrombus without a stent retriever, with lysis times increasing with stent retriever diameter. Two mechanisms of clot lysis were established: axial and radial permeation. Axial permeation from the clot front was the primary mechanism of lysis in all configurations, as it facilitated increased protein binding with fibrin fibres. Introducing a stent retriever channel allowed for radial permeation, which occurred at the fluid-thrombus interface, although lysis was much slower in the radial direction because of weaker secondary velocities. Conclusions: Numerical models can be used to better understand the complex physiological relationship between IVT and MT. Two different mechanisms of lysis were established, providing a basis towards improving the efficacy of combined treatments.