Simulation-based optimisation for the generative design of a shunt.

This project falls within the EPSRC research area of healthcare technologies while also including topics pertinent to mathematical and engineering sciences. The project will be under the supervision of Prof Antoine Jerusalem (engineering) and Prof Sarah Waters (mathematics) and will work with optimisation tools provided by Prof Jose-Maria Peña through Lurtis Ltd, with clinical guidance provided by Mr Jay Jayamohan. Hydrocephalus is a serious medical condition affecting one in every thousand births. Though arising from various causes, hydrocephalus describes an excess of fluid within the skull, causing a build-up of inter-cranial pressure. If left untreated, the condition will worsen, causing headaches, balance problems, and potentially proving fatal within years. The most common treatment is to implant a permanent drainage shunt into the brain to remove excess fluid to the stomach, where it can be safely cleared. However, this treatment has the risk of vascular brain tissues such as the Choroid Plexus (CP) being dragged into the shunt during drainage, causing both shunt blockages and bleeds in the brain, and additionally preventing the shunt from being easily replaced. A new shunt design is needed to avoid this. The intention of the DPhil is, therefore to create a new, patentable (potentially personalisable) design framework for hydrocephalus shunts, suitable for clinical use. The project will first develop a computational fluid model for the shunt-CP system within the brain, before using generative design principles to optimise the configuration for a given CP idealised geometry. Generative design is a novel approach which combines traditional engineering with advanced artificial intelligence methods (mostly machine learning and heuristic optimisation methods) to produce new tentative designs and refine the ones proposed by the user. Here a heuristic optimisation algorithm developed in partnership with Lurtis is used (based on hybrid self-adaptive optimisation techniques that combine population-based and local search strategies). For this optimisation framework, this DPhil may also explore different surrogate-based approaches that would complement the optimisation mechanism for this particular computational model problem. The model is posed as a fluid-structure interaction problem where outflow through the shunt creates fluid stresses, which causes deflection of the CP tissue. With a sufficiently generalisable mesh, various material parameters can be varied to investigate reduction in this deflection, hence minimising the likelihood of the tissue being entangled in the shunt holes. The optimisation code acts as a black-box wrapper, which can be coupled to the shunt model to investigate parameters of interest and personalised for a given morphology. Work during the short project provided a proof of concept with a simplified 2D model. This project developed an investigative model which successfully simulated the deformation of CP in the hydrocephalus scenario. The optimisation algorithm was used successfully to propose new hole sizes and positions, and suggested that larger diametrically opposite holes would minimise tissue deflection. There is also potential within the scope of a DPhil to create a software tool which could apply these methods to general medical components of a similar remit. We may want to explore and justify our models by comparing simulations to physical experiments run with the engineering department. If the project progresses sufficiently, we may also want to establish contact with medical companies to discuss patent and manufacturing opportunities.

The main impact of the SABS CDT will be the difference made by the scientists trained within it, both during their DPhils and throughout their future careers.

The impact of the students during their DPhil should be measured by the culture change that the centre engenders in graduate training, in working at the interface between mathematical/physical sciences and the biomedical sciences, and in cross sector industry/academia working practices.

Current SABS projects are already changing the mechanisms of industry academic collaboration, for example as described by one of our Industrial Partners

"UCB and Roche are currently supervising a joint DPhil project and have put in two more joint proposals, which would have not been possible without the connections and the operational freedom offered by SABS-IDC and its open innovation culture, a one-of-the-kind in UK's CDTs."

New collaborations are also being generated: over 25% of current research projects are entirely new partnerships brokered by the Centre. The renewal of SABS will allow it to continue to strengthen and broaden this effect, building new bridges and starting new collaborations, and changing the culture of academic industrial partnerships. It will also continue to ensure that all of its research is made publically available through its Open Innovation structure, and help to create other centres with similar aims.

For all of our partners however, the students themselves are considered to be the ultimate output: as one our partners describes it,

"I believe the current SABS-IDC has met our original goals of developing young research scientists in a multidisciplinary environment with direct industrial experience and application. As a result, the graduating students have training and research experience that is directly applicable to the needs of modern lifescience R&D, in areas such as pharmaceuticals and biotechnology."

However, it is not only within the industrial realm that students have impact; in the later years of their DPhils, over 40% of SABS students, facilitated by the Centre, have undertaken various forms of public engagement. This includes visiting schools, working alongside Zooniverse to develop citizen science projects, and to produce educational resources in the area of crystal images. In the new Centre all students will be required to undertake outreach activities in order to increase engagement with the public.

The impact of the students after they have finished should be measured by how they carry on this novel approach to research, be it in the sector or outside it. As our industrial letters of support make clear, though no SABS students have yet completed their DPhils, there is a clear expectation that they will play a significant role in shaping the UK economy in the future. For example, as one of our partners comments about our students

"UCB has been in constant search for such talents, who would thrive in pharmaceutical research, but they are rare to find in conventional postgraduate programmes. Personally I am interested in recruiting SABS-IDC students to my group once they are ready for the job market."

To demonstrate the type of impact that SABS alumni will have, we consider the impact being made by the alumni of the i-DTC programmes from which this proposal has grown. Examples include two start-up companies, both of which already have investment in the millions. Several students also now hold senior positions in industry and in research facilities and institutes. They have also been named on 30 granted or pending patents, 15 of these arising directly from their DPhil work.

The examples of past success given above indicate the types of impact we expect the graduates from SABS to achieve, and offer clear evidence that SABS students will become future research leaders, driving innovation and changing research culture.