Imaging Cardio-Mechanical Health

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

Abstract

Heart failure (HF) and coronary heart disease (CHD) are major clinical conditions affecting an estimated 2.7M people in the UK alone. Both of these conditions result in a fundamental reduction in the ability of heart muscle to effectively pump and deliver blood to the body. While this deficiency in the heart is easily detected using medical imaging, dissecting the causes of reduced heart performance in terms of its implications for muscle health remain an open challenge for the treatment of heart failure and evaluation of patient treatment.

The Imaging Cardiomechanical Health (ICMH) project aims to address this need by directly measuring the health of the heart muscle through the development of cardiac Magnetic Resonance Elastography (cMRE). Using state-of-the art magnetic resonance imaging and biomechanical modelling, this project will provide a novel noninvasive modality (cMRE) for directly measuring the alterations in muscle properties, determining the mechanical pathophysiology behind reduced function. Integrating new imaging sequences with biomechanical processing software, this project will aim to systematically develop, verify and validate these tools using 3D printed and ex vivo animal heart models. Building on these engineering developments, cMRE tools developed through the ICMH project will be applied in patients and volunteers to illustrate the potential of this new modality.

Planned Impact

The central aim of this project is the development of robust clinical tools for the in vivo measurement of the intrinsic active and passive biomechanical properties of cardiac tissue using magnetic resonance elastography (MRE) in conjunction with advanced biomechanics. Delivery of cMRE technology would provide a new mode for assessing muscle health in clinical treatment and biomedical research, presenting pathways for improving clinical outcomes and reducing economic costs.

Impact in the Clinic: Current assessment of heart health is based on echocardiography or MRI surrogates of pump function. These analyses inherently measure the health of the cardiovascular system as a whole and are nontrivially modulated by multiple factors - e.g. vascular hypertension, microvascular disease, and preload failure - that may obscure the health of the myocardium itself. While cardiac pressure catheterisation permits a more thorough and direct assessment of the heart muscle, the invasiveness of the method often means its use is delayed until patients show significant heart failure symptoms. Due to the associated risks, the catheterisation process is only repeated in specific patients post-treatment, limiting the assessment of patient-specific treatment efficacy. Development of our cMRE technology would alter each step of this process. The non-invasive nature of our technique would allow its safe use at early disease stages, providing a clear assessment of tissue health distinct from the rest of the cardiovascular system. This complementary information could be integrated into clinical diagnosis procedures, improving patient stratification as well as focusing therapies to address problems identified within the muscle of the heart. Further, the procedure could be safely repeated, allowing re-assessment of tissue health during treatment. This would enable low-risk, longitudinal guidance for adjusting therapy through time. These improvements would also come at significantly reduced cost (£350 / 1hr MRI scan time) compared to pressure catheterisation (£1250 / procedure, equipment and in-patient time).

Impact in Clinical / Basic Research: A core outcome of this project is a novel tool for assessing the properties of the heart - and other tissues - non-invasively. This would provide a valuable tool for research in both clinical and basic science arenas as explained in Academic Beneficiaries and Academic Impact sections. Realizing 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).

Economic Impact: The economic impact of the proposed work will be realised through commercial opportunities stemming from the project (see National Importance). Development and dissemination of these tools will require commercialisation to absorb costs associated with device manufacturing, installation and CE marking. Our team at KCL has experience in these development procedures, being currently involved with the European Union-funded PICTURE project, where new transducer technology for the assessment of breast tumours has entered into the patent process. These initial efforts in development of MRE transducer design and reconstruction has already generated interest from 12 clinical sites worldwide as well as interest from imaging companies (Siemens and Philips). Use of our technology would require specific, engineered wave transducer technologies (current devices in our lab have been designed for brain, heart, liver and cells) as well as installation of our sequences and FEM-based reconstruct tools. Delivering these solutions to clinical, experimental and engineering end-users would necessitate commercialisation (see Pathways to Impact).

Publications

10 25 50
publication icon
Asner L (2017) Patient-specific modeling for left ventricular mechanics using data-driven boundary energies in Computer Methods in Applied Mechanics and Engineering

publication icon
Bertoglio C (2018) Relative pressure estimation from velocity measurements in blood flows: State-of-the-art and new approaches. in International journal for numerical methods in biomedical engineering

publication icon
Capilnasiu A (2019) Magnetic resonance elastography in nonlinear viscoelastic materials under load. in Biomechanics and modeling in mechanobiology

publication icon
Fovargue D (2018) Stiffness reconstruction methods for MR elastography. in NMR in biomedicine

publication icon
Hessenthaler A (2017) Validation of a non-conforming monolithic fluid-structure interaction method using phase-contrast MRI. in International journal for numerical methods in biomedical engineering

 
Description Significant work has gone into the design of new transducers capable of providing precise wave stimulation through the body. We have developed a transducer that is now capable of delivering waves to the heart through chest and gives reliable signal.

Additional investment has gone into advanced sequences which can enable imaging of wave motion through the heart. We currently have developed a sequence that triggers to the heart that can be acquired with 4 breath holds. This sequence uses a range of innovative MR sequence developments to reduce acquisition time and improve imaging quality.
Further investment has gone into design of reconstruction technology for interpreting wave motion and deducing myocardial stiffness properties. This technology has been demonstrated in phantom tests. We are currently advancing the reconstruction to exploit reduced data in order to reduce the acquisition time in patients / volunteers. This reconstruction involves image processing as well as physics-based image analysis. This is currently being tested on a range of phantoms. Currently, we are examining this technique in patients and volunteers to examine systolic / diastolic stiffness characteristics in vivo, with the idea of extending this for use in clinical studies through funders, such as the British Heart Foundation.
Exploitation Route Our technology is being shared as part of a sister project (EU funded H2020 project, FORCE) with clinical sites across Europe. Our hardware is soon to be available as a commercial product for a leading MRI vendor. Our software and sequence will soon be used for clinical studies.
Sectors Healthcare

 
Description The findings of this study have been used in the development of new transducer hardware for MRE elastography that was being explored as part of a spin out company and we had begun selling this hardware technology to clinical centres around the world. Currently, however, we are not licensing this technology to a major MRI vendor in the community who has elected to adopt our hardware for elastography.
First Year Of Impact 2018
Sector Healthcare
Impact Types Economic

 
Description Healthcare Technology Challenge Award 2018
Amount £1,376,343 (GBP)
Funding ID EP/R003866/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 03/2018 
End 03/2022
 
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
 
Title MRE Transducer / Sequence Development 
Description We have developed new sequences for elastography in the heart as well as new transducer hardware for stimulation of waves in the chest. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2017
Development Status Under active development/distribution
Impact Equipment as been disseminated to 3 different clinical sites and is now being evaluated in animals. 
 
Description Academic Visit to MOX (Milano, Italy) 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact This was a visit to speak with potential collaborators working on cardiac modelling and mechanics at MOX in Politecnico di Milano. For this visit, I gave a lecture and spent two days engaging with students / staff on a range of issues in modelling within the heart.
Year(s) Of Engagement Activity 2018
URL https://mox.polimi.it/elenco-seminari/?id_evento=1693&t=763721&ricerca=
 
Description Academic Visit, University of Glasgow (Glasgow, United Kingdom) 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was an invited lecture given to academics at the University of Glasgow to present research and build collaborations.
Year(s) Of Engagement Activity 2018
URL https://www.gla.ac.uk/schools/mathematicsstatistics/events/?groupID=12
 
Description CMBE (Pittsburgh, USA) 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Two presentations on cardiac research will be presented
Year(s) Of Engagement Activity 2017
 
Description Cardiac Physiome (Toronto, Canada) 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This is one of the leading conferences in cardiac modelling and simulation. At this conference we presented 1 oral presentation.
Year(s) Of Engagement Activity 2018
URL http://www.cardiacphysiome.org/meetings/2017-cardiac-physiome-workshop/
 
Description ECCM / ECFD 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 one of the more significant modelling and simulation conferences in Europe, focusing on mechanics and hemodynamics. At this conference, we are presenting 2 oral presentations.
Year(s) Of Engagement Activity 2018
URL http://www.eccm-ecfd2018.org/
 
Description ECCOMAS Conference (Crete) 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Three talks were presented at the meeting regarding cardiac research.
Year(s) Of Engagement Activity 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 (Hawaii, USA) 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Two presentations are given regarding cardiac work and MRE reconstruction technology.
Year(s) Of Engagement Activity 2017
 
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 MEIBioeng and MPEC (London, United Kingdom) 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This is one of the growing conferences on Biomedical Engineering in the UK, promoting the field and networking researchers. For this conference, we gave 1 keynote lecture.
Year(s) Of Engagement Activity 2018
URL https://www.ipem.ac.uk/ConferencesEvents/MPECMEIbioeng2017.aspx
 
Description Royal Society Summer Exhibition 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact This is based on the Heart in your Hands project, illustrating heart function to the broader public.
Year(s) Of Engagement Activity 2017
 
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