EPSRC Centre for Multiscale Soft Tissue Mechanics - with application to heart & cancer

In the diagnosis and treatment of disease, clinicians base their decisions on understanding of the many factors that contribute to medical conditions, together with the particular circumstances of each patient. This is a "modelling" process, in which the patient's data are matched with an existing conceptual framework to guide selection of a treatment strategy based on experience. Now, after a long gestation, the world of in silico medicine is bringing sophisticated mathematics and computer simulation to this fundamental aspect of healthcare, adding to - and perhaps ultimately replacing - less structured approaches to disease representation.

The in silico specialisation is now maturing into a separate engineering discipline, and is establishing sophisticated mathematical frameworks, both to describe the structures and interactions of the human body itself, and to solve the complex equations that represent the evolution of any particular biological process. So far the discipline has established excellent applications, but it has been slower to succeed in the more complex area of soft tissue behaviour, particularly across wide ranges of length scales (subcellular to organ).

This EPSRC SoftMech initiative proposes to accelerate the development of multiscale soft-tissue modelling by constructing a generic mathematical multiscale framework. This will be a truly innovative step, as it will provide a common language with which all relevant materials, interactions and evolutions can be portrayed, and it will be designed from a standardised viewpoint to integrate with the totality of the work of the in silico community as a whole. In particular, it will integrate with the EPSRC MultiSim multiscale musculoskeletal simulation framework being developed by SoftMech partner Insigneo, and it will be validated in the two highest-mortality clinical areas of cardiac disease and cancer.

The mathematics we will develop will have a vocabulary that is both rich and extensible, meaning that we will equip it for the majority of the known representations required but design it with an open architecture allowing others to contribute additional formulations as the need arises. It will already include novel constructions developed during the SoftMech project itself, and we will provide many detailed examples of usage drawn from our twin validation domains. The project will be seriously collaborative as we establish a strong network of interested parties across the UK. The key elements of the planned scientific advances relate to the feedback loop of the structural adaptations that cells make in response to mechanical and chemical stimuli. A major challenge is the current lack of models that operate across multiple length scales, and it is here that we will focus our developmental activities. Over recent years we have developed mathematical descriptions of the relevant mechanical properties of soft tissues (arteries, myocardium, cancer cells), and we have access to new experimental and statistical techniques (such as atomic force microscopy, MRI, DT-MRI and model selection), meaning that the resulting tools will bring much-need facilities and will be applicable across problems, including wound healing and cancer cell proliferation.

The many detailed outputs of the work include, most importantly, the new mathematical framework, which will immediately enable all researchers to participate in fresh modelling activities. Beyond this our new methods of representation will simplify and extend the range of targets that can be modelled and, significantly, we will be devoting major effort to developing complex usage examples across cancer and cardiac domains. The tools will be ready for incorporation in commercial products, and our industrial partners plan extensions to their current systems.

The practical results of improved modelling will be a better understanding of how our bodies work, leading to new therapies for cancer and cardiac disease.

Computers are increasingly being used to help doctors diagnose and treat disease, and new software is being developed to allow individual, patient-specific therapies. For this approach to be successful, two key issues need to be addressed. These are fundamental mathematical modelling to understand the biomechanical changes that occur in soft tissue in disease, and the development of techniques to deal with uncertainty in clinical measurements. SofTMech will carry out programmes of research by world-leading UK experts to give answers to these problems and, by developing detailed models of remodelling in the heart following a myocardial infarction (MI) and metastasis of breast carcinoma, provide computational examples that will enable healthcare technologists to translate the research into software to be used in clinical practice.

Heart disease is the leading killer in the world, responsible for about 30% of all deaths each year. Cancer is the second deadliest disease, and the World Health Organization projects that without immediate action, the global number of deaths from cancer will increase by nearly 80% by 2030. Together, these pose severe economic and medical challenges for the UK health care system. Consequently, SofTMech's research will have a major socioeconomic healthcare impact on the quality of life and health in the UK, and beyond, and enhance the UK's global competitiveness by addressing the most important healthcare problems. It is therefore of direct benefit to everyone in terms of improved quality of life and more efficient and cost-effective patient-specific treatment.

Our research will generate a range of new mathematical models for studying these diseases. Developing predictive quantitative models of healing processes after a heart attack and of the biomechanics of cancer invasion will facilitate translational medical research to enhance diagnosis, treatment, and prevention. By developing test- and data-based modelling, we will examine how cellular changes affect stress and strain distributions within organs, what drives functional responses within cells, and which parameters are strongly associated with adverse remodelling leading to heart failure or cancer metastasis. This fundamental research will significantly advance our understanding of disease pathogenesis, diagnosis and responses to therapy, and hence move clinical research forward. This will be of direct benefit to patients and healthcare providers. For example, we will focus on developing in-depth myocardium mechanics models, linked to important subcellular organelle remodelling, that will increase our understanding of the mechanical status of a heart with a MI and help us suggest treatments to prevent progression of this disease to terminal heart failure. As a further example, we will explain how cancer cells become softer and thus better able to spread through surrounding tissue, to provide new targets for interventional therapies.

International engineering-software companies that provide computer code to describe the behaviour of advanced materials, such as our partners Simulia (Abaqus) and Ansys, and their customers in advanced technologies worldwide will benefit from advanced mathematical models that predict the behaviour of soft materials that SofTMech will develop, by incorporating these models into their widely used commercial software packages. Major medical imaging companies including Siemens, another of our partners, will benefit from using our models to better interpret signals from e.g. magnetic resonance and ultrasound scanning devices, which will further benefit patients and their doctors.

The Centre will raise awareness of our research to new and existing groups by networking activities, increase knowledge transfer by involving new clinical/industrial partners through training events, and influence the effectiveness of public services and policy by engagement with the Turing Gateway.