Development and Application of Very-High-Field (3 Tesla) Clinical Cardiovascular Magnetic Resonance Methods

Lead Research Organisation: University of Oxford
Department Name: Central Admin - Research Services

Abstract

Lay summary: Patients with heart disease currently undergo a number of different tests, all of which have problems in terms of quality of information, patient safety (radiation, invasiveness), and availability. Cardiovascular magnetic resonance (CMR) is an extremely versatile advanced new imaging technique in Medicine. This method can, in principle, provide highly accurate information on the structure and pump function of the heart, on whether the heart muscle is well supplied with nutrients and oxygen, and on whether portions of it that have stopped functioning (pumping) are still alive (stunned) or dead (scar). However, current CMR systems, which work at a magnetic field strength of 1.5T, are limited in the amount of information they can provide. We have obtained one of the first CMR systems, which uses a much higher field strength, 3T, and propose to develop new CMR methods that would be of major help to examine patients with heart disease. These methods should provide the information needed by Cardiologists to manage their patients with optimum clinical outcomes, and free from risk to the patient. Such new imaging techniques would not only substantially improve the care of patients with heart disease, but would also be used in clinical research, to yield new insight into how heart disease develops and how it should best be treated. Our work should therefore contribute substantially to improving cardiovascular health and to relieving the burden of cardiovascular disease, the number one killer in the U.K.

We have established a web site (www.cardiov.ox.ac.uk/ocmr/ocmr.htm) to promote the activities of our group and to disseminate our findings. If the application is successful, the lay summary will be placed on the website, which will be updated as the milestones are reached.

Technical Summary

Cardiovascular magnetic resonance (CMR) is an extremely versatile technique that has recently begun to play a substantial role both in clinical research and in diagnostic Cardiology, and a number of important initial clinical observations have been made with this technique. However, CMR is currently performed at field strengths of up to 1.5 Tesla, where its versatility cannot be fully exploited due to limited signal-to-noise. We propose to develop an array of sophisticated clinical CMR methods at very-high-field strength (3 Tesla), and to apply them in important clinical research studies, for multiparametric characterisation of the normal and diseased cardiovascular system: Regional myocardial perfusion will be quantified both with first-pass and arterial spin labelling methods, myocardial oxygenation will be assessed by developing high-resolution BOLD imaging techniques; the diagnostic potential of these techniques for detecting coronary artery disease will be tested in patients. 23Na-MRI will be developed and applied in studies assessing myocardial viability with this intrinsic contrast method. Ultrashort TE-based methods will be developed and applied, for the first time, to directly image tissue fibrosis and calcification by MR. High-resolution 31P-MR spectroscopy techniques will be developed at rest and during stress, and will be applied to define the role of cardiac energetics in coronary artery disease. Finally, high-resolution vascular imaging, developed at 3 Tesla and including ultrashort TE methods, will be developed and validated, to substantially advance our capability for non-invasive characterisation of plaque composition in clinical studies of atherosclerosis. We believe that this programme would result in both an array of important novel cardiac imaging techniques and fundamentally new insight into the pathophysiology of cardiovascular disease, achieving both substantially more sophisticated phenotyping in clinical research studies and potential widespread application in diagnostic Cardiology. Our work should therefore contribute significantly to improving cardiovascular health and to relieving the burden of cardiovascular disease.

Publications

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Hogan MC (2007) Effects of steady state free precession parameters on cardiac mass, function, and volumes. in The international journal of cardiovascular imaging

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Hudsmith LE (2007) Assessment of left atrial volumes at 1.5 Tesla and 3 Tesla using FLASH and SSFP cine imaging. in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance

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Hudsmith LE (2009) (31)P cardiac magnetic resonance spectroscopy during leg exercise at 3 Tesla. in The international journal of cardiovascular imaging

 
Description SCMR President 2006-2008 - directing the international specialist society in the field
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact This role involved many facets and was wide ranging directing the effort of this specialist group. Cardiac MR is emerging and new improved approaches appear year on year, and the SCMR is the organisation that distils the methods into best practice via its conferences and journals.
 
Description Senior author of the first detailed standards for CMR reporting in clinical practice (JCMR 2009;11(1):5)
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact This work defines how cardiac MR should be reported and will provide improved cardiac diagnoses with fewer errors and improved efficiency.
 
Description Stefan Neubauer is member of an international expert group on Simplifying Cardiovascular MR Pulse Sequence Terminology
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description 7T Programme Grant
Amount £1,304,942 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 01/2011 
End 12/2015
 
Description Assessment of myocardial fibre structure in hypertrophic cardiomyopathy with magnetic resonance diffusion tensor imaging
Amount £297,659 (GBP)
Funding ID FS/12/32/29559 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2012 
End 10/2015
 
Description Characterisation of 3D time-resolved intra-cardiac blood flow in the failing heart using advanced cardiovascular magnetic resonance techniques
Amount £284,852 (GBP)
Funding ID FS/12/14/29354 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2012 
End 07/2015
 
Description Dr James Moon, London Heart Hospital 
Organisation University College London Hospital
Country United Kingdom 
Sector Public 
PI Contribution We provide the shortened shMOLLI sequence to support the work at the London Heart into Extra-cellular Volume fraction (ECVF) that they are doing on cardiac patients. The also use our method in assessing the T1 before MR contrast agents are used in patient groups with whom we hav elittle or no access
Collaborator Contribution Our partners have provided training in the use of the ECV method that we can use this approach in Oxford. Most valuably they have provided data on a number of interesting patient groups to whom the shMOLLI method has been found to offer new insights into disease. These insights have strengthened our understanding of what our new T1 mapping methods are showing.
Impact Large number of abstracts that are moving into full papers. Single breath-hold Vd(m) calculation as good as multi breath-hold technique in Equilibrium Contrast CMR Daniel Sado, Stefan K Piechnik, Matthew D Robson, Viviana Maestrini, Andrew Flett, Steven K White, Sanjay M Banypersad, James Moon Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):P262 (1 February 2012) Age and gender dependence of pre-contrast T1-relaxation times in normal human myocardium at 1.5T using ShMOLLI Stefan K Piechnik, Vanessa Ferreira, Adam J Lewandowski, Ntobeko Ntusi, Daniel Sado, Viviana Maestrini, Steven K White, Merzaka Lazdam, Rajarshi Banerjee, Mark B Hofman, James Moon, Stefan Neubauer, Paul Leeson, Matthew D Robson Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):P221 (1 February 2012) Histological validation of ShMOLLI equilibrium contrast CMR for the measurement of diffuse myocardial fibrosis Steven K White, Stefan K Piechnik, Stefan Neubauer, Matthew D Robson, James Moon Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):O111 (1 February 2012) Pre-contrast T1 mapping for detection of myocardial fibrosis in asymptomatic and symptomatic aortic stenosis Sacha Bull, Steven K White, Stefan K Piechnik, Andrew Flett, Vanessa Ferreira, Margaret Loudon, Jane M Francis, Stefan Neubauer, James Moon, Saul Myerson Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):P93 (1 February 2012) Pre-contrast ShMOLLI T1 mapping in cardiac AL amyloidosis Theodoros Karamitsos, Sanjay M Banypersad, Daniel Sado, Viviana Maestrini, Vanessa Ferreira, Stefan K Piechnik, Matthew D Robson, Philip N Hawkins, Stefan Neubauer, James Moon Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):O76 (1 February 2012)
Start Year 2010
 
Description Hammersmith Hospital, Prof. Paolo Camici 
Organisation Hammersmith Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution We have evaluated patients using MRI that have been evaluated using PET at the Hammersmith site. This has allowed us to evaluate the 3T MRI perfusion and BOLD methods against the gold standard of PET.
Collaborator Contribution They have provided the PET expertise
Impact This work has provided significant new knowledge about these methods and has results in a high-profile publication: PMID: 19920032
Start Year 2007
 
Description Prof. Christopher Kramer, HCMR study 
Organisation University of Virginia (UVa)
Country United States 
Sector Academic/University 
PI Contribution A large consortium to study the value of cardiac MRI in hypertrophic cardiomyopathy for risk stratification
Collaborator Contribution Kramer: North American Chief Investigator. Myself, European Chief Investigator
Impact $14.3m NIH grant, 2013-2018
Start Year 2012
 
Description Prof. Michael Jerosch-Herold, Harvard Medical School 
Organisation Harvard University
Department Harvard Medical School
Country United States 
Sector Academic/University 
PI Contribution Made measurements of myocardial blood flow on a number of disease states
Collaborator Contribution Expert on measurement of absolute myocardial perfusion by MRI, they helped us analyse our data.
Impact Several publications, see list of publications. Multidisciplinary, i.e. collaboration between clinicians and MY physicists
 
Title shMOLLI method to Siemens 
Description We developed a T1 mapping method that we have used our 3T and 1.5T systems to validate. These methods have been taken on by Siemens Healthcare and have been incorporated into their clinical product (presently as a works-in-progress package, but this is likely to become part of their mainstream product). 
Type Diagnostic Tool - Imaging
Current Stage Of Development Small-scale adoption
Year Development Stage Completed 2010
Development Status Under active development_distribution
Impact The diagnostic imaging method that we have developed allows images to be collected faster that results in more reliable image quality. Further more we generate quantitative maps of relaxation parameters from these measurements in real-time which has been found to be a very useful tool in the clinic and appears to improve diagnosis on various clinical patient groups. 
 
Company Name Perspectum Diagnostics 
Description The company has been set-up to rapidly translate liver imaging techniques designed in the university into clinical products used on patients. To date the company has been capitalised via the private sector and has won a Technology Strategy Board grant. It has continued to survive and grow and now employs ~50 people. It has FDA (US regulator) clearance to sell its products in the USA. It has a US office and sales team. It continues to develop IP, win competitive grants and sell into the market place. For more information http://perspectum-diagnostics.com/ or use google! 
Year Established 2012 
Impact In March 2014 Perspectum won a Technology Strategy Board grant valued at around £1.2M. In march 2015, Perspectum won a contract with Galectin Therapeutics as part of their phase 2 trial. In June 2015, Perspectum achieved ISO 9001 In July 2015, Perspectum won a Horizon 2020 phase 1 grant to develop their products for children and adolescents with chronic liver disease. In Nov 2015, Perspectum added FDA clearance to its CE-marked product which allows it to sell into the important US clinical market. Perspectum Diagnostics was founded in partnership with the University of Oxford in 2012 after a ground-breaking study demonstrated the potential of T1 mapping to predict liver fibrosis. Dr Rajarshi Banerjee, then a clinical researcher at the University and now CEO of Perspectum Diagnostics, explains: "Magnetic Resonance Imaging in the liver is not a new concept. Research in the 1980's showed that there was some correlation between T1 values and liver disease. However, the liver has a tendency to store iron in quantities that are sufficient to alter the T1 signal, rendering it ineffective in many cases. Together with Prof Matthew Robson and other scientists at the Oxford Centre for Cardiovascular Magnetic Resonance Research, we developed our now patented technology which uses multiple parametric measurements to correct for differences in iron storage. This enabled the creation of our novel liver inflammation and fibrosis (LIF) score which correlates closely with the current gold standard of staging fibrotic liver disease, liver biopsy. We also found that the technique is particularly good at spotting early disease, which is essential in allowing patients to make lifestyle alterations before they progress to potentially irreversible cirrhosis. As a physician, I wanted to bring this technology to clinicians worldwide, helping them to slow the huge burden of liver disease. In 2012, we took the decision to commercialise the technology (branded as LiverMultiScan) and Perspectum Diagnostics was created. " Since its initial release in 2015, LiverMultiScan has achieved CE and FDA certification and has been installed on four continents. Using this remarkable technology, we have analysed more than 6000 images, and partnered with pharmaceutical companies in both clinical and preclinical trials. A recent study suggested that the technology predicts clinical outcomes in patients with chronic liver disease Why not be part of the next chapter of the Perspectum story?
Website http://perspectum-diagnostics.com/
 
Description Presentation at open day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Presentation to a large group using images and video showing how cardiac MRI works and how it is valuable in diagnosing cardiac disease. Informal Q&A session at the end.

There was great interest and several people were interested in volunteering (as normals) for future studies.
Year(s) Of Engagement Activity 2009,2012,2013
 
Description Summer School visit MDR 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact We hosted a site visit for a Summer School that focused on cardiac engineering. http://mpss.iop.org/index.html

This involved a 2 hour visit to our site where we performed live demonstrations on MRI scanning and presented talks on what the method could offer clinically.

The talks and presentations were very well received, and our scores in the end of course assessment were at the 80% level, which we were told was very high.
Year(s) Of Engagement Activity 2012