Atherosclerosis stratification using advanced imaging and computer-based models

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

Abstract

The goal of the proposed project is to develop a novel tool for atherosclerosis risk stratification. Cardiovascular disease
(CVD) via atherosclerotic plaque rupture (coronary artery disease (CAD) and stroke) is the leading single cause of
morbidity and mortality in the Western world. Vascular atherosclerotic disease is a causative factor in a high percentage of
CVD events. Widely accepted risk markers that allow predicting cardiovascular events such as myocardial infarction and
stroke are currently based on risk factors such as smoking, weight and blood pressure. These lifestyle factors and medical
conditions are derived from population based studies and are linked to an average probability of having a CV event, but do
not measure the individual's personal risk, and are therefore can result in potential overtreatment.
The main deliverable from this project will be a computational tool to assess the grade of atherosclerosis of an individual
person using multi-parametric magnetic resonance imaging (MRI) in combination with biophysical computer models.
Advanced imaging with Magnetic Resonance will be used for plaque burden measurement and plaque component
characterization in order to identify the risk of rupture and the systemic atherosclerosis burden. The team will use exiting
MRI methods in combination with novel markers of plaque vulnerability. These markers include: plaque volume, intraplaque
haemorrhage, lipid content, calcification, endothelial permeability and extracellular volume. In addition, biophysical
models will be used to predict biomechanical properties related to atherosclerotic changes in the vascular system. The
team will investigate and compute markers such as wall shear stress, particle residence time and arterial wall stiffness,
which can give further insight into atherosclerosis development. For the first time, different parameters from modelling and The goal of the proposed project is to develop a novel tool for atherosclerosis risk stratification. Cardiovascular disease
(CVD) via atherosclerotic plaque rupture (coronary artery disease (CAD) and stroke) is the leading single cause of
morbidity and mortality in the Western world. Vascular atherosclerotic disease is a causative factor in a high percentage of
CVD events. Widely accepted risk markers that allow predicting cardiovascular events such as myocardial infarction and
stroke are currently based on risk factors such as smoking, weight and blood pressure. These lifestyle factors and medical
conditions are derived from population based studies and are linked to an average probability of having a CV event, but do
not measure the individual's personal risk, and are therefore can result in potential overtreatment.
The main deliverable from this project will be a computational tool to assess the grade of atherosclerosis of an individual
person using multi-parametric magnetic resonance imaging (MRI) in combination with biophysical computer models.
Advanced imaging with Magnetic Resonance will be used for plaque burden measurement and plaque component
characterization in order to identify the risk of rupture and the systemic atherosclerosis burden. The team will use exiting
MRI methods in combination with novel markers of plaque vulnerability. These markers include: plaque volume, intraplaque
haemorrhage, lipid content, calcification, endothelial permeability and extracellular volume. In addition, biophysical
models will be used to predict biomechanical properties related to atherosclerotic changes in the vascular system. The
team will investigate and compute markers such as wall shear stress, particle residence time and arterial wall stiffness,
which can give further insight into atherosclerosis development. For the first time, different parameters from modelling and The goal of the proposed project is to develop a novel tool for atherosclerosis risk stratification. Cardiovascular disease
(CVD) via atherosclerotic plaque rupture (coronary artery disease (CAD) and stroke) is the leading single cause of
morbidity and mortality in the Western world. Vascular atherosclerotic disease is a causative factor in a high percentage of
CVD events. Widely accepted risk markers that allow predicting cardiovascular events such as myocardial infarction and
stroke are currently based on risk factors such as smoking, weight and blood pressure. These lifestyle factors and medical
conditions are derived from population based studies and are linked to an average probability of having a CV event, but do
not measure the individual's personal risk, and are therefore can result in potential overtreatment.
The main deliverable from this project will be a computational tool to assess the grade of atherosclerosis of an individual
person using multi-parametric magnetic resonance imaging (MRI) in combination with biophysical computer models.
Advanced imaging with Magnetic Resonance will be used for plaque burden measurement and plaque component
characterization in order to identify the risk of rupture and the systemic atherosclerosis burden. The team will use exiting
MRI methods in combination with novel markers of plaque vulnerability. These markers include: plaque volume, intraplaque
haemorrhage, lipid content, calcification, endothelial permeability and extracellular volume. In addition, biophysical
models will be used to predict biomechanical properties related to atherosclerotic changes in the vascular system. The
team will investigate and compute markers such as wall shear stress, particle residence time and arterial wall stiffness,
which can give further insight into atherosclerosis development. For the first time, different parameters from modelling and imaging will be integrated into one clinical tool for comprehensive and individual risk stratification on different assessment
levels.

Planned Impact

From a societal and from the individual perspective cardiovascular disease (CVD) is the leading public health problem in
the US, in Europe and in the UK. In particular, CVD caused 40% of all deaths in the United Kingdom in 2002 with an overall
CVD cost to the EU economy of almost £166 billion and the US economy $297.7 billion per year. In the UK, the socioeconomic
costs have been estimated to be £29.1 billion in 2004. Since 1990, the number of prescriptions for antiplatelet
drugs for atherosclerosis treatment has increased steadily to over 38 million prescriptions in England every year. The
number of prescriptions for lipid lowering drugs is more than fifteen times higher than a decade ago. In 2011
antihypertensive drugs were the most prescribed drugs for CVD in England, Scotland and Wales. The cost of prescriptions
for hypertension and heart failure therapy totalled to just over £330 million between 2010 and 2011. Better imaging based
atherosclerosis risk stratification could result in a better personalized understanding of risk, and in significant cost
reductions due to the avoidance of unnecessary prescriptions. Patients would directly benefit from an individually stratified
treatment strategy allowing optimal selection for surveillance, medical or surgical treatment.
The benefit to the UK economy beyond healthcare economics will be twofold. Firstly, the project will employ additional staff
in the UK through the academic partner. Philips staff will be working on the project based in the UK, contributing to tax
income. Secondly, revenue streams are expected to Philips UK companies leading to taxable profits. Philips has a strong
presence in the UK healthcare sector and additional sales of a newly developed package as described in this project will
lead to an increase in the profits of Philips UK business. Licensing of IP generated during the project from KCL to Philips
will generate additional revenue streams for KCL. Philips and KCL collaborate the framework of a hub strategy which
integrates industrial software development with academic research centres on-site for short clinical feedback loops. The
proposed project strengthens the KCL imaging research hub and attracts R&D investment of a global company to the UK.
The joint spin-off company that could be founded as UK LC after successful completion of the project would generate
revenues on a case-based business model (see appendix A of the application for details). Revenues from sales of
technology developed during the project are expected already immediately after completion of the project on a small scale
by targeting research customers. The full business potential including a reimbursement scenario can be leveraged
following successful outcome trials subsequent to this project. We will establish a link with the King's Imaging Technology
Evaluation Centre (KITEC), which supports the work of the Medical Technologies Evaluation Programme (MTEP) and the
Diagnostic Assessment Programme (DAP) of the National Institute for Health and Care Excellence (NICE). Projects
undertaken by KITEC include randomized controlled trials, systematic reviews, establishment of registers and databases.
The scientific methodology results from this research will be output as research publications in high-impact journals in the
field of medical imaging. Target journals will include Circulation, Journal of the American College of Cardiology, Magnetic
Resonance in Medicine and Journal of Cardiovascular MR. Dissemination will also take place through presentations at the
major international conferences, especially the American Heart Association, the International Society for Magnetic
Resonance in Medicine (ISMRM) and The Society for Cardiovascular Magnetic Resonance (SCMR).

Publications

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publication icon
Van Engelen A (2017) Aortic length measurements for pulse wave velocity calculation: manual 2D vs automated 3D centreline extraction. in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance

 
Description We have developed a new pulse wave velocity software that allows to automatically find the centre line in a vessel and to calculate the pulse wave velocity based on phase contrast MR measurements acquired at two different vascular locations. The data can also be output in a format that can be used to perform 1D simulations of blood flow and pressure. In addition, we have developed tissue classification software to assign different tissue types such as lipid core, calcification, fibrosis, intraplaque haemorrhage and normal tissue. The software is based on classic classification algorithms but also on machine and deep learning based approaches.
Exploitation Route The software has been implemented in the Philips Discovery platform and will be maintained by Philips scientists and product engineers.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description So far there was little non-academic impact of our research but we foresee great potential for improving image analysis in the clinical setting and will shortly start a clinical study to demonstrate the usefulness of our new vascular software suite to characterise atherosclerotic plaque (e.g. stiffness, calcification, lipid accumulation) in patients with symptomatic and asymptomatic carotid artery disease.
First Year Of Impact 2016
Sector Digital/Communication/Information Technologies (including Software),Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
Description In Vivo Spectral Photon Counting CT MolecularImaging in Cardio- and Neuro-Vascular Diseases - SPCCT
Amount £248,977 (GBP)
Funding ID 668142 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2016 
End 12/2019
 
Description Motion Corrected Reconstruction for 3D Cardiac Simultaneous PET-MR Imaging: Towards Efficient Assessment of Coronary Artery Disease
Amount £608,658 (GBP)
Funding ID EP/N009258/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 02/2016 
End 01/2019
 
Description Multi-sequence MRI characterisation of deep vein thrombosis in man
Amount £129,000 (GBP)
Funding ID PG/15/89/31793 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2016 
End 03/2018
 
Description Multidimensional and Multiparametric Quantitative Cardiac MRI from Continuous Free-Breathing Acquisition
Amount £565,581 (GBP)
Funding ID EP/P032311/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 09/2017 
End 08/2021
 
Description Regulatory T-cell therapy for Orthotopic Heart Transplantation in Children
Amount £99,950 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2015 
End 08/2016
 
Description Self-Navigated Multi-Contrast And Quantitative Whole Heart 3D Magnetic Resonance Imaging
Amount £974,560 (GBP)
Funding ID EP/P007619/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 02/2017 
End 01/2021
 
Description SmartHeart "Next-generation cardiovascular healthcare via integrated image acquisition, reconstruction, analysis and learning"
Amount £5,127,775 (GBP)
Funding ID EP/P001009/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2016 
End 09/2021
 
Description Thymus derived Tregs expanded in vitro as a treatment for paediatric heart transplant patients to prevent cardiac allograft vasculopathy
Amount £230,159 (GBP)
Funding ID TG/16/2/32657 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 12/2018
 
Description Wellcome EPSRC Centre for Medical Engineering
Amount £2,147,483,647 (GBP)
Funding ID NS/A000049/1 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
End 04/2022
 
Description PARISk consortium 
Organisation Maastricht University (UM)
Country Netherlands 
Sector Academic/University 
PI Contribution We are validating plaque classification and vessel border detection algorithms developed in this project with the annotated data provided by the partners in Maastricht and Rotterdam.
Collaborator Contribution We have access to magnetic resonance imaging data of patients with carotid artery plaque that have been annotated based on results of previous studies where histology served as the goldstandard.
Impact So far there no outcomes yet but we will use the imaging data to validate our own imaging findings.
Start Year 2015
 
Description PARISk consortium 
Organisation University Medical Center Rotterdam
Country Netherlands 
Sector Hospitals 
PI Contribution We are validating plaque classification and vessel border detection algorithms developed in this project with the annotated data provided by the partners in Maastricht and Rotterdam.
Collaborator Contribution We have access to magnetic resonance imaging data of patients with carotid artery plaque that have been annotated based on results of previous studies where histology served as the goldstandard.
Impact So far there no outcomes yet but we will use the imaging data to validate our own imaging findings.
Start Year 2015
 
Description Pint of Science activity in London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We presented our work at the Pint of Science in London where we had several talks about the use of medical imaging for the diagnosis and treatment of heart disease.
Year(s) Of Engagement Activity 2016
 
Description Royal Society Summer Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact We took part of the Royal Society Summer Science Festival and had a stand demonstrating our research in cardiovascular imaging called "Heart in your Hands". Several hundred people attended our stand every day and all attendees were very engaged with our PhD students and postdocs who explained our research in lay words.
Year(s) Of Engagement Activity 2017