Adaptive, Multi-scale, Data-Infused Biomechanical Models for Cardiac Diagnostic and Prognostic Assessment

Lead Research Organisation: King's College London
Department Name: Imaging & Biomedical Engineering

Abstract

Driven by structural and functional abnormalities in the muscle of the heart, Heart Failure (HF) is a complex syndrome affecting around 900,000 people in the UK. HF results in a fundamental reduction in the ability of heart muscle to effectively pump and deliver blood to the body. While this deficiency in pump function is easily observed using medical imaging, dissecting the underlying cause of this reduced performance in terms of its implications for muscle structure and function remain open challenges. Further, predicting how disease will progress or respond to therapy remains an unmet need that would substantially improve patient care.

Using state-of-the art biomechanical modelling, the "Adaptive, Multi-scale, Data-Infused Biomechanical Models for Cardiac Diagnostic and Prognostic Assessment" project will address these challenges by providing a modelling framework for assessment of the heart. Uniting measurements from microscopy, rheology, and medical imaging, this project aims to create biomechanical models that provide detailed information on the structure and function of the heart aiding diagnosis. Further, the platform will provide infrastructure for predictive modelling, simulating the response and adaptation of the heart over time. Biomechanical models will be systematically validated using animal heart models, providing rich data for understanding the biomechanics in vivo and ex vivo. The framework will, further, be directly translated through a novel study in patients with hypertrophic cardiomyopathy, providing a test bed for validation of predictive models of disease progression and response to therapy through virtual surgery.

Planned Impact

The central aim of this project is to bring biomechanical modelling and analysis to the clinic. This will be achieved through the development of an adaptive, multiscale, data-infused biomechanical modelling framework that will facilitate diagnostic and prognostic assessment in the failing heart. This framework will provide a new, and rigorously validated, mechanism for assessing the structural and functional characteristics of the heart in vivo. Additionally, the developed framework will provide a platform for predictive modelling that accounts for remodelling responses observed in animal and human studies conducted through the project. Delivery of this technology would provide a new mode for characterising the heart and optimising treatment, presenting pathways for improving clinical outcomes and reducing economic costs.

Impact in Clinical / Basic Research: A core outcome of this project is a biomechanical modelling infrastructure that enables assessments of the heart muscle and predictive simulation of heart function through time. This would provide a valuable tool for research in both clinical and basic science arenas as explained in Academic Beneficiaries and Academic Impact sections. Realising this potential, the developments in this project - which require interdisciplinary input - extend to a broad range of potential end users, enabling the cross-pollination of ideas through training workshops and education programmes (see Pathways to Impact). I will also utilise the assembled network of project partners, working in a range of complementary fields, to ensure that outcomes of this work are maximised.

Economic Impact: The proposed work builds a fundamental biomechanical infrastructure for diagnostic and prognostic modelling. Achieving the aims of this work, my team will demonstrate the capacity to use personalised biomechanical models to assist in patient stratification as well as perform predictive modelling of patient outcomes due to progression of disease or surgical intervention. These demonstrative first results would garner significant interest. While the economic impact of the work is likely to follow the grant, I will liaise through our department's commercialisation officer (Neil Simrick) to explore potential opportunities. I will also explore my connections with Siemens (and Siemens Image guided therapy), to maximise the potential benefits of this work.
 
Description We have been working to understand the mechanical response of tissues, focusing on characteristics that are commonly observed but often ignored. We've developed new descriptive models that replicate behaviours observed in experiments. We've also focused on models that unify currently conflicting datasets, showing that a single model representation can replicate the bulk behaviours observed over many experiments. To enable uptake of these models, we've also developed new mathematical approximations that allow one to efficiently simulate these materials.
Exploitation Route We are developing methods that will be generally applicable for the biomechanics and modelling community. These techniques will enable new simulations that were previously limited due to computational expense and lack of strong foundational models.
Sectors Healthcare

 
Description Partnership with ETH 
Organisation ETH Zurich
Country Switzerland 
Sector Academic/University 
PI Contribution Starting a collaborative imaging study. We have provided techinical expertise and hardware for elastography within a porcine study.
Collaborator Contribution Partners at ETH are managing data acquisition and proper ethics around the animal study.
Impact Planned publications and future engagement across new projects.
Start Year 2016
 
Description Partnership with INSERM 
Organisation National Institute of Health and Medical Research (INSERM)
Country France 
Sector Public 
PI Contribution We are designing new hardware, software and analysis tools for the combined use of biomechanics and rheology in the MRI.
Collaborator Contribution Partners have provided equipment (MRI) as well as tailored sequences to work with newly developed hardware and software.
Impact The key outputs of this work will be the ability to test tissues (cardiac and cancerous tissues) and examine the effects of microstructure on the biomechanics of the tissue. This will be used to study heart disease and cancer. The project is inherently multi-disciplinary. The project has also gained independent funding for a post-doc.
Start Year 2018
 
Description Partnership with Queen Mary University London 
Organisation Queen Mary University of London
Department William Harvey Research Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Access to material testing and rheology equipment for characterization of phantom materials.
Collaborator Contribution Access to equipment and expertise
Impact Testing of materials for linking biomechanics across measurement modalities.
Start Year 2016
 
Description Partnership with TU Graz 
Organisation Graz University of Technology
Department Institute of Biomechanics
Country Austria 
Sector Academic/University 
PI Contribution This partnership has enabled access to human myocardial tissue data as well as prospective analysis and tissue testing in porcine myocardium.
Collaborator Contribution Access to testing equipment and expertise.
Impact Planned publications and future prospective collaborations through grant-funding.
Start Year 2016
 
Description ESMC (Bologna, Italy) 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This conference is represents one of the most significant conferences for Solid mechanics in europe. At this conference we will be presenting 1 oral presentation.
Year(s) Of Engagement Activity 2018
URL http://www.esmc2018.org/drupal8/
 
Description ISMRM (Paris, France) 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a scientific meeting that is one of the most significant for MRI. At this conference, we will present 1 poster, 2 e posters, 2 oral talks and 1 power pitch to the general assembly. The aim in this conference is to garner support / collaborations with both research and industry partners.
Year(s) Of Engagement Activity 2018
URL https://www.ismrm.org/18m/
 
Description World Congress of Biomechanics (Dublin, Ireland) 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This constitutes the biggest single conference for biomechanics, which occurs every 4 years. At this conference we are presenting the keynote lecture in cardiac mechanics.
Year(s) Of Engagement Activity 2018
URL http://wcb2018.com