Physical Sciences for Health CDT
Thesis project - "Experimental and computational investigation of the mechanisms of deep venous thrombosis"
Dr Daniele Vigolo: School of Chemical Engineering (Experimental fluid dynamics of multiphase flows)
Dr Alessio Alexiadis: School of Chemical Engineering (Computational fluid dynamics)
Dr Alexander Brill: Institute of Cardiovascular Science (Thrombosis and modelling of disease)
Prof Gerard Nash: Institute of Cardiovascular Science (Blood rheology)
Deep venous thrombosis (DVT) is a dangerous and painful condition in which blood clots form in the deep veins. These clots (thrombi) can become unstable, detach and travel to the lungs, resulting in a life threatening complication called pulmonary embolism (PE). In the UK, DVT and PE cause an estimated 25,000 deaths annually which is about five times the combined number of deaths from breast cancer, acquired immunodeficiency syndrome and traffic accidents. The mechanisms of clot development in the veins remains very unclear, however researchers predict it could be related to blood flow around the flaps of the valves within veins. It is also clear the DVT is likely to occur through prolonged periods of immobility (e.g. long haul flights); this is thought to be related to insufficient pumping from muscles which normally assist the heart in pumping blood around the body. The aim of this project is to identify key factors which increase the likelihood of thrombus formation looking particularly at the geometry of the veins and valves as well as the composition of the blood. The investigation of these parameters will be carried out by developing the physical sciences computationally and experimentally.
The physical science development will be utilising an advancing field called microfluidics which exploits the fabrication of small channels (typical size of tens or hundreds of microns) to study the movement of fluids for chemical reactions, single cell analysis, flow simulations, mimicking biological flows, etc. For the purpose of this project we will design and fabricate a microfluidic device that mimics the geometry of veins within mice. As blood is not transparent, alternative particle suspensions shall be investigated, which will simulate the composition of blood (cells and water) and its rheological properties. This should highlight how the geometry and blood composition affect thrombus formation within a miniaturised model.
The computational development will be advancing on the conventional computational fluid dynamic modelling systems using a novel technique called discrete multi-hybrid system (DMHS). The aim will be to develop a computational simulation of flow taking into account flexible boundaries (e.g. valves) to understand the flow properties of blood within different geometries (i.e. vein side branches/back branches) to help pin point key parameters within the geometry of veins which increases the likelihood of clot formation.
Once the miniaturised model has set key parameters which increase the likelihood of thrombus formation it will then be possible to upscale into a life size model, using 3D printing to fabricate a copy of a human vein and upgrading the computational model to a larger scale. This will give rise to more challenges that will need understanding and overcome, however this will be more appropriate for a clinical setting.
Identification of a set of biomarkers linking vessel geometry and/or blood composition to high risk of DVT would be of great interest in the clinical setting. Success would lead to design of studies in human cohorts to evaluate associations with occurrence or outcome of DVT, ultimately to optimise thrombosis prevention or establish new therapeutic targets. The project will also pave the way to wider applications of physical and computational modelling to problems of the cardiovascular system where blood rheology, mechanical properties of blood vessels and adhesion between cells are relevant.