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In silico characterisation of venous valve dynamics


Project Description

The role of the venous valve in venous haemodynamics remains poorly understood. However, changes in valve behaviour have been identified as factors associated with a number of venous disorders including deep vein thrombosis and chronic venous insufficiency. Venous valves promote venous return from the lower limb and ensure drainage of the superficial to the deep venous circulation. Analysis of valve dynamics requires a fluid-structure interaction (FSI) approach to represent both the valve leaflet tissue (solid) and the local blood flow (fluid). This project will use these techniques to develop models of valve behaviour under a range of physio- and patho-logical conditions. A parametric approach will be used to define valve geometry, to allow project outcomes to be integrated with data from imaging methodologies such as ultrasound. The sensitivity of valve function to parameters associated with valve geometry (local valvular stenosis and valve sinus geometry) and material properties (vein wall and valve leaflets) will be investigated in silico to determine target parameters for in vivo assessment of valve function using imaging techniques. Due to the computational expense of FSI approaches the project will investigate the potential of the 3D model to derive reduced-order 1D models of venous valve behaviour.

Research hypothesis:
• Variability in venous valve geometry, material properties and local environment contributes to risk factors for valve-related disease through impaired valve function

Objective:
• Develop a 3D Fluid-Structure Interaction (FSI) model of the venous valve and local environment
• Assess influence of valve geometry and material properties on effectiveness of valve function using a formal sensitivity analysis
• Use 3D FSI to inform improved reduced-order valve representation for 1D modelling applications in venous haemodynamics

The project will address four tasks. Training in month 1-6 will include a literature review, introduction to numerical techniques and review of existing approaches for FSI modelling (e.g. OpenFOAM, ANSYS, Alya) including definition of benchmarks. The student will benefit from tailored DTP activities offered by Insigneo, training associated with specific software packages and High Performance Computing resources associated with the CompBioMed EU H2020 project (www.compbiomed.eu).

T1 Benchmarking cases for FSI problems (M4-M9): will assess the capability of different FSI approaches using a set of benchmark cases of increasing complexity, generating outputs for a conference submission and consolidating skills in programming and code deployment.

T2 Assessment of influence of valve material properties and geometry on solid mechanics (M5-M16): will focus on the solid mechanics of the valve, investigating the influence of the complexity of the material model used (linear elastic, hyperelastic, iso-/aniso-tropic). Unlike the aortic valve, limited data is available for venous valves below the level of gross anatomy. This project will develop new hypotheses related to valvular solid mechanics that can inform future experimental investigations of valve microstructure. The specific focus of this task will be to assess the sensitivity of the open and closed valve configuration to the material properties.

T3 Assessment of influence of valve geometry on fluid mechanics and FSI analyses (M8-M29): will extend T2 to include the fluid mechanics local to the valve, initially using a non-compliant fluid-only approach informed by the geometries generated in T2. This will be developed to a full FSI analysis of the full valve cycle to capture opening and closing dynamics and self-excited oscillations of the leaflets in the open configuration, reported in vivo (1).

T4 Sensitivity analysis of FSI valve model (M20-M30): will characterise the sensitivity of valve function to the material properties, valvular and venous geometry (including valve sinus) and loading conditions. The initial scope of the sensitivity analysis will be informed by the computational cost of the 3D FSI model and outcomes reported using a 1D model (2), this will be refined to include additional parameters associated with the 3D model from T2/T3.

T5 Integration of 3D FSI approach with reduced order models of venous valves/venous haemodynamics (M28-M36): This task will investigate the feasibility of integrating outcomes from T4 within reduced order models of valve dynamics2 and informing boundary conditions of the local 3D model with 1D models of the venous circulation. This task will identify potential clinical applications of the modelling framework as targets for funding applications.

T2, T3 and T4 will generate one publication each. M37-PM42 : finalisation of thesis.

Enquiries:
Interested candidates should in the first instance contact Dr Andrew Narracott ()

How to Apply:
Please complete a University Postgraduate Research Application form available here: http://www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select Department of Infection, Immunity and Cardiovascular Disease as the department.

Funding Notes

The Faculty of Medicine, Dentistry and Health has received an allocation of three EPSRC studentships for 2019 entry from the Doctoral Training Partnership grant that is awarded to the University of Sheffield to fund PhD studentships in the EPSRC remit. These studentships will be 42 months in duration, and include home fee, stipend at RCUK rates and a research training support grant (RTSG) of £4,500.

Home/EU students must have spent the 3 years immediately preceding the start of their course in the UK to receive the full funding.

Interviews are due to take place on Monday 25th March 2019.

References

(1) Lurie F, Kistner RL, Eklof B, Kessler D. Mechanism of venous valve closure and role of the valve in circulation: a new concept. J Vasc Surg. 2003 Nov;38(5):955-61.
(2) Keijsers JMT, Leguy CAD, Huberts W, Narracott AJ, Rittweger J, Vosse FNV. Global sensitivity analysis of a model for venous valve dynamics. Journal of Biomechanics. 2016; 49(13) : 2845-2853. doi: 10.1016/j.jbiomech.2016.06.029

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