EPSRC Centre for New Mathematical Sciences Capabilities for Healthcare Technologies

Lead Research Organisation: University of Liverpool
Department Name: Mathematical Sciences

Abstract

As quality of life constantly improves, the average lifespan will continue to increase. Underlining this improvement is the vast amount of the UK government's support to NHS (£133.5 billion in year 2011/12) and the UK pharmaceutical industry's R&D large investment (4.9 billion to R&D in year 2011/12). The expectation of quality healthcare is inevitably high from all stakeholders. Fortunately recent advances in science and technology have enabled us to work towards personalised medicine and preventative care. This approach calls for a collective effort of researchers from a vast spectrum of specialised subjects.
Advances in science and engineering is often accompanied by major development of mathematical sciences, as the latter underpin all other sciences. The UoL Centre will consist of a large and multidisciplinary team of applied and pure mathematicians, and statisticians together with healthcare researchers, clinicians and industrialists, collaborating with 15 HEIs and 40 NHS trusts plus other industrial partners and including our strongest groups:
MRC Centre in Drug Safety Science, Centre for Cell imaging (CCI for live 3D and 4D imaging), Centre for Mathematical Imaging Techniques (unique in UK), Liverpool Biomedical EM unit, MRC Regenerative Medicine Hub, NIHR Health Protection Research Units, MRC Hub for Trials Methodology Research.
Several research themes are highlighted below:
Firstly, an improved understanding of the interaction dynamics of cells and tissues is crucial to developing effective future cures for cancer. Much of the current work is in 2D, with restrictive assumptions and without access to real data for modelling. We shall use the unparalleled real data of cell interactions in a 3D setting, generated at UoL's CCI. The real-life images obtained will have low contrast and noise and they will be analysed and enhanced by our imaging team through developing accurate and high resolution imaging models. The main imaging tools needed are segmentaton methods (identifying objects such as cells and tissues regions in terms of sizes, shapes and precise boundaries). We shall propose and study a class of new 3D models, using our imaging data and analysis tools, to investigate and predict the spatial-temporal dynamics.
Secondly, better models of how drugs are delivered to cells in tissues will improve personalised predictions of drug toxicity. We shall combine novel-imaging data of drug penetration into 3D experimental model systems with multi-scale mathematical models which scale-up from the level of cells to these model systems, with the ultimate aim of making better in-vitro to in-vivo predictions.
Thirdly, there exist many competing models and software for imaging processing. However, for real images that have noise and are of low contrast, few methods are robust and accurate. To improve the modelling, applied and pure mathematicians team up to consider using more sophisticated tools of hyperbolic geometry and Riemann surfaces and fractional calculus to meet the demand for accuracy, and, applied mathematicians and statisticians will team up to design better data fidelity terms to model image discrepancies.
Fourthly, resistance to current antibiotics means that previously treatable diseases are becoming deadly again. To understand and mitigate this, a better understanding is needed for how this resistance builds up across the human interaction networks and how it depends on antibiotic prescribing practices. To understand these scenarios, the mathematics competition in heterogeneous environments needs to be better understood. Our team links mathematical experts in analysing dynamical systems with experts in antimicrobial resistance and GPs to determine strategies that will mitigate or slow the development of anti-microbial resistance.
Our research themes are aligned with, and will add value to, existing and current UoL and Research Council strategic investments, activities and future plans.

Planned Impact

Our team of applied, pure mathematicians and statisticians together with healthcare researchers, clinicians and industrialists will collaborate with 15 HEIs and 40 NHS trusts plus other industrial partners. Therefore the impact on the wide community is more pronounced and immediate than a responsive mode grant.

Academic impact. To the healthcare community, the proposed work will provide an insightful understanding of personalised medicine and preventative care. To the mathematical sciences community, the proposed work will advance several new directions in mathematics and statistics that will lead to high impact publications and high profile public addresses at major conferences. We see researchers in these communities as direct beneficiaries of the Centre.

The primary means of reaching out to users is by our User Engagement Forum via a series of Knowledge Exchange activities including visitor programmes; advisory service and maths and healthcare 'clinics'; summer schools; pump priming projects and activities to engage HEIs and industries; impact and public engagement activities; joint seminar series; workshops around specific problems. Some will be run with other EPSRC centres.

Economic Impact. The UK pharmaceutical industry in 2007 contributed £8.4 billion to the UK's GDP, investing 4.3 billion to R&D which is the third-highest share of global pharmaceutical R&D. The NHS budget for the UK was £133.5 billion in 2011/12 and medicines account for 10% of the NHS budget i.e. £13.4 billion. The Centre will make major contributions to UK R&D:
(i). Aided by image technologies, understanding the progression of the disease process is important to enable the industry target relevant biological processes. (ii). Incorporation of protein/cell level dynamics into tissues is necessary and essential to predict the overall toxicity. This study will lead to treatments optimised for specific patients. The pharmaceutical industry interests in drugs with less side-effects and atified medicine. It will benefit from this Centre's new analysis tools and the UoL's MRC Centre in Drug Safety Science and MRC Regenerative Medicine Hub and Trials Hub in terms of extensive experimental data, computational simulations and scientific insights on tissues; therefore, we expect this impact to continue to be facilitated with our long-term collaborative partners and new parties to perform proof-of-principle trials.

Through existing and established connections, we would build further engagement including conversion of our results into commercial products.

Societal Impact. Cancer is due to uncontrolled growth and spread of abnormal cells. Our proposed work, aiming for better understanding of cells and tissues, is crucial to combat cancer. There were 14M new sufferers (8M deaths) with 338K in UK alone in 2012. Research impact is of massive scale.

With aging, plaque due to cholesterol, calcium, and fibrous tissue can build up in arteries and due to such, they can narrow and stiffen. Coronary angioplasty and stenting are to improve blood flow in the body's arteries and veins, with 75,000 procedures performed in England per year. Our study will optimise designs to minimise side effects. It will be conducted with clinicians. Benefit and publicity to NHS are immediate.

There is considerable concern in the society with common infectious diseases, which lead to 300M illnesses and more than 5M deaths each year worldwide with Ebola outbreak well-known and anti-microbial resistance posed as massive challenge. Finding a model for it by scaling up from small/local network information to large/global networks to understand diseases' network is of vital importance to Healthcare policy makers and service providers.

We will use these to engage the public at annual Science Festivals. We believe that these will not only raise awareness of the complexity in disease networks, but also generate interest in the community fascinated by bio-mimic system.

Publications

10 25 50
 
Title collaboration with music composer Emily and launch of PRISM 
Description PRiSM is the RNCM Centre for Practice & Research in Science & Music PRiSM brings together a number of creative collaborations between the sciences and music. PRisM was launched the 04/10/2017 with "The Music of Proof" performance 
Type Of Art Performance (Music, Dance, Drama, etc) 
Year Produced 2017 
Impact Dr Howard music composition has been influenced by discussion with mathematicians and biologists 
URL https://www.rncm.ac.uk/research/research-centres-rncm/prism/
 
Description The project started 20 months ago and so no PDRAs have finished from here yet:

1. T1 Project 1 (stenting). We have found a relationship between stents' size and damage to the stents in operating conditions. This is through
constructive description of favourable and unfavourable conditions for endovascular sealing of abdominal aortic aneurysms and by our analysis tool developed at LCMH. The finding is published in Proceedings of the Royal Society and the Nature Sci Report.

2. T2 Project 1 (segmentation using partial priors). We have designed reliable minimal path-following algorithms to produce an accurate segmentation
which is much faster than the usual fully 3D models. The speed-up is from dimension reduction while the reliability is by achieving non-intersecting paths.

3. T2 Project 2 (multi-modality image co-registration). We have found new models for aligning images which are much better than the established models based on normalized gradients or mutual information.
Exploitation Route Through our projects partners and new collaborators, as well as engagement activities. They participate the projects directly. We run regular networking events to engage national and international collaborators.
Sectors Communities and Social Services/Policy,Digital/Communication/Information Technologies (including Software),Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://tinyurl.com/EPSRC-LCMH
 
Description The Centre grant aims to tackle healthcare challenges proposed by clinicians and industrialists by novel mathematics. Thus each started project (two so far) has aimed for direct impact to healthcare sector, specifically (1) the Stenting project (Theme 1 Project 1) has produced initial results that can be used by clinicians to facilitate selection of stents towards personalization. (2) the Interactive Segmentation project (Theme 2 Project 1) has also produced impressive results (as with directly industrial involvement) and the collaborating partner will start formal validation process this year to aim for adoption into products. Our work will potentially impact future NHS diagnostic tools and platforms from which we take pride. (3) the influenza project (Theme 3 Project 1) is developing National scale population models of influenza sub-type transmission, infection and immunity. World Health Organization data will be used to infer key parameter values pertaining to antigenic drift rates and subtype transmission and interactions. A workshop is being planned for summer 2017 to engage with policy makers and other stakeholders.
First Year Of Impact 2017
Sector Digital/Communication/Information Technologies (including Software),Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description A Dragonfly multimodal fast imaging platform with SRRF-stream (Super-Resolution Radial Fluctuation) in the Liverpool Centre for Cell Imaging (CCI)
Amount £450,000 (GBP)
Funding ID BB/R01390X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 05/2018 
End 04/2019
 
Description ARTFUL Statement of Need (SoN) for a mid range facility (MRF)
Amount £507,705 (GBP)
Funding ID EP/R007926/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2017 
End 04/2022
 
Description EPSRC - iCASE studentship (Smith Institute)
Amount £86,000 (GBP)
Funding ID EPSRC Voucher 17000203 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2017 
End 09/2021
 
Description EPSRC First Grant Scheme (Dr T Valkonen) Centre New lecturer
Amount £168,000 (GBP)
Funding ID EP/P021298/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 03/2017 
End 03/2019
 
Description MRC Skills Development Fellowships
Amount £2,000,000 (GBP)
Funding ID SDF/Williamson 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 11/2017 
End 12/2020
 
Description Newton Research Collaboration Programme Award
Amount £16,660 (GBP)
Funding ID NW/CHEN 
Organisation Royal Academy of Engineering 
Sector Learned Society
Country United Kingdom
Start 03/2017 
End 03/2018
 
Description Collaboration with Public Health England 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution Scoping work to identify research questions of direct relevance to PHE regarding influenza evolution and transmission within the UK.
Collaborator Contribution Provided time for meetings
Impact Paper submitted: "Using propensity score estimation in an adjusted study design for estimating indirect and direct vaccine effectiveness in observation studies, with application to rotavirus vaccination". Multi-disciplinary (epidemiology, mathematics, socio-demographic modelling, medicine).
Start Year 2016
 
Description Project with Oculus 
Organisation Oculus
Country Germany 
Sector Private 
PI Contribution Plan of a project to further develop a non contact tonometer (Corvis ST) produced by Oculus
Collaborator Contribution Full funding in addition to provision of technical and clinical data
Impact Fully funded industrial project - initial results are very promising - this is a high profile project that can make a significant impact on our standing in the ocular biomechanics community
Start Year 2013
 
Description Theme 1 (Multi-scale Modeling) Project 1 
Organisation Royal Liverpool University Hospital
Department Department of Vascular Service
Country United Kingdom 
Sector Hospitals 
PI Contribution We provided the vital mathematical modeling and analysis of the stenting problem
Collaborator Contribution Designed and Participated in the project. Helped establishing industrial links to the Centre.
Impact - 1 research paper - 1 joint workshop - 1 EPSRC industrial iCase studentship award
Start Year 2015
 
Description Theme 2 (Imaging and Data Integration) Project 1 
Organisation Mirada Medical Ltd
Country United Kingdom 
Sector Private 
PI Contribution We are providing the analysis model, mathematical techniques and software for image analysis
Collaborator Contribution Helped the design of this industrial project whcih has mathematical challenge to tackle
Impact - Draft papers being finalized - Test software almost ready for industrial validation
Start Year 2015
 
Description Theme 3 Collaboration with World Health Organization 
Organisation World Health Organization (WHO)
Country Global 
Sector Public 
PI Contribution Modelling seasonal influenza incidence and evolutionary dynamics. . Participation in bi-weekly teleconference calls. This (hopefully) will also lead to engagement when we relay our findings back to WHO.
Collaborator Contribution WHO are providing up-to-date data gathered from their surveillance system. Participation in bi-weekly teleconference calls.
Impact Ongoing work
Start Year 2016
 
Description Theme 3 Collaboration with World Health Organization 
Organisation World Health Organization (WHO)
Country Global 
Sector Public 
PI Contribution Modelling seasonal influenza incidence and evolutionary dynamics. . Participation in bi-weekly teleconference calls. This (hopefully) will also lead to engagement when we relay our findings back to WHO.
Collaborator Contribution WHO are providing up-to-date data gathered from their surveillance system. Participation in bi-weekly teleconference calls.
Impact Ongoing work
Start Year 2016
 
Description workshop focused on cell imaging and image analysis 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Centre for Cell Imaging organised a 2 day workshop focused on light microscopy techniques and image analysis. 90 researchers and students attended the event mainly from Liverpool and Manchester but also from other Universities in the UK. Industrial partners were invited and the director of the Advanced Imaging Centre at the HHMI Janelia Research Campus, Teng-Leong Chew gave a keynote lecture and a comprehensive hands-on training session on Image Analysis.
Year(s) Of Engagement Activity 2017
URL https://cci.liv.ac.uk/2017_workshop.html
 
Description British Applied Mathematics Colloquium. BAMC 2017, University of Surrey, UK (April 10-12, 2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The talk delivered is S. Frecentese, G. Carta, L.P. Argani, A.B. Movchan, N.V. Movchan, M.L. Wall, "Bloch waves in
blood vessels with stents"
Year(s) Of Engagement Activity 2017
 
Description British Science Festival - Public engagement and outreach 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The Centre is keen to explain what we do to the public. In 2007, we took part in this Public engagement and outreach. A. Movchan and L. Argani have presented an event at the British Science Festival, Mathematical Events 2017. Brighton, 5-9 September 2017 (Friday 8 September, 16.30-17.30, A2, Asa Briggs Arts, University of Sussex), entitled ``Towards better aneurysm treatments'', which attracted a lot of interest from experts and members of the general public.
Year(s) Of Engagement Activity 2017
URL https://www.britishscienceassociation.org/british-science-festival
 
Description Centre workshop 1 - Sept 2016 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Imaging workshop where we reported our projects and findings, invited industrial partners to tell us their challenges in their work.
The networking event is well received.
Year(s) Of Engagement Activity 2016
URL http://www.tinyurl.com/EPSRC-LCMH
 
Description Centre workshop 2 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Stenting for abdominal aortic aneurysms - modeling experts met clinicians and industrial partners and new / potential collaborators.
New results are highlighted and new problems are identified.
Year(s) Of Engagement Activity 2017
URL http://www.tinyurl.com/EPSRC-LCMH
 
Description Co-supervision of PhD student 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Co-supervision of PhD student Hawre Salih by Prof Ke Chen, Dr Tuomo Valkonen and Dr Anna Pratoussevitch.
Year(s) Of Engagement Activity 2017,2018
 
Description European Symposium on Vascular Biomaterials - ESVB 2017, Strasbourg, France (October 12-14, 2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact L.P. Argani, F. Torella, R.K. Fisher, R.G. McWilliams, M.L. Wall, A.B. Movchan, "Modelling of
deformation and dynamic response of abdominal aortic aneurysms treated by endovascular
sealing"
- L.P. Argani was selected among the 8 finalist for the Young Researcher Prize
Year(s) Of Engagement Activity 2017
 
Description Infectious Disease Modelling Summer School 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Two week-long workshop held in Japan for public health practitioners and graduate students to develop a practical understanding of infectious disease modelling. Read was delivered sessions on seasonal influenza epidemiology and modelling epidemics in structured populations. Audience was drawn from Japan as well as other countries in the region (including South Korea, China, Indonesia, Philippines).
Year(s) Of Engagement Activity 2016
URL https://sites.google.com/site/modelinfection/home/shortcourse3
 
Description Interdisciplinary EPSRC Workshop "Elastic deformation and dynamic response of aneurysm repairs: modelling and applications" (Liverpool, UK, February 2017) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This interdisciplinary workshop attracted leading scientists, applied mathematicians and medical practitioners from the UK, USA, Netherlands, Italy. The workshop has focused on the practical and theoretical aspects of abdominal aortic aneurysms, and in particular EVAS treatment. The Liverpool group and their partners have contributed six presentations to this event: S. Frecentese, "Modelling of waves in stented blood vessels"
L.P. Argani, "Modelling of deformation and dynamic response of abdominal aneurysm
sealing"
F. Torella, "Introduction to AAA, EVAR and EVAS"
R.K. Fisher, "Modes and mechanisms of failure of EVAR/EVAS"
R.G. McWilliams, "Methods of imaging surveillance after EVAS/EVAR"
M.L. Wall, "Aneurysm rupture - theoretical and practical challenges"
Year(s) Of Engagement Activity 2017
 
Description Invited Seminar, EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited seminar at the EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter. Useful discussions during and afterwards which have highlighted important new techniques that could help optimise my current approach.
Year(s) Of Engagement Activity 2017
 
Description Invited presentation at the International Conference for the In Vitro Toxicology Society, London. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation at the International Conference for the In Vitro Toxicology Society, London. Useful discussions afterwards with potential future collaborators. Also, a number of followup meetings planned to develop future collaborations.
Year(s) Of Engagement Activity 2017
 
Description Invited visit to present work at Unilever 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Invited visit to present work at Unilever. Useful discussions that has helped align my work with more relevant industrial impact. Discussions ongoing regarding development of future collaborations and shared grant applications.
Year(s) Of Engagement Activity 2017
 
Description Presentation on Emergence risks associated with A(H7N9) Avian Influenza in China. Venue: USA State Department 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact A(H7N9) Avian Influenza in China workshop
Year(s) Of Engagement Activity 2017
 
Description The Vascular Societies' Annual Scientific Meeting 2017, Manchester Central, UK (November 22-24, 2017) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk delivered at the meeting was S. Frecentese, G. Carta, L.P Argani, A.B. Movchan, N.V. Movchan, M.L. Wall, "Wave
propagation and fluid-structure interaction in stented blood vessels"
Year(s) Of Engagement Activity 2017
 
Description Workshop 4 (T3) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact A workshop is being planned for summer 2017 to engage with policy makers and other stakeholders.
The subject of AMR modeling and influenza modeling is a major healthcare topic that is studied at the Liverpool Centre.
Year(s) Of Engagement Activity 2017
URL http://www.tinyurl.com/EPSRC-LCMH
 
Description workshop 3 (Imaging) jointly with Cambridge CMIH Centre 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This is a joint event with and held in Cambridge.
The teams from all 5 UK centres will be represented, excellent example of UK coherent research efforts in tackling imaging problems.
Year(s) Of Engagement Activity 2017
URL http://www.turing-gateway.cam.ac.uk/event/tgmw42