Expansion of state-of-the-art MR imaging infrastructure for pulmonary disease stratification: POLARIS

Lead Research Organisation: University of Sheffield
Department Name: Infection Immunity & Cardiovasc Disease

Abstract

Summary of POLARIS
The unique combination of expertise in technology development and the proven ability to translate new technologies into pioneering clinical studies at the University of Sheffield forms the basis of this application for funding. We have long-standing high-level collaborations with both Hospital Trusts in Sheffield (Sheffield Teaching Hospital and Sheffield Children's Hospital) that allow us to apply our developments in all age groups. This has established Sheffield as a national clinical referral centre for image based understanding of lung diseases, but our work has also enabled other centres within the UK to roll out the methods for the benefit of a much wider group of patients. This application is particularly timely with the award of the NIHR Research Professorship to Jim Wild in 2013, which will facilitate the national uptake of the technology at other centres. The expansion of our gas polarisation facilities enabled by this grant will have many benefits for our collaborating centres including creation of a national distribution facility for hyperpolarised gases for those centres that don't have their own polarisation facilities. The ongoing methodological research, clinical evaluations and work with drug companies performed on the planned new state-of-the art 1.5T scanner will ensure that the UK becomes the leading nation in this important area of diagnostic medicine.

Technical Summary

SEE SUMMARY

Planned Impact

This investment in imaging, hyperpolarisation and computing infrastructure will help consolidate Sheffield and the UK as an international centre of excellence for hyperpolarised MRI and a clinical centre of excellence for pulmonary imaging.

Publications

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Billings CG (2017) Incremental shuttle walk test distance and autonomic dysfunction predict survival in pulmonary arterial hypertension. in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

 
Description MHRA specials licence for hyperpolarised gas manufacture - Pathway for diagnostic lung imaging with hyperpolarised gases
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact Opened a diagnostic pathway for referral of patients with respiratory disease for sensitive functional lung imaging using hyperpolarised gas MRI in Sheffield. This is a world first to clinical practice for this technology. Patients have been referred from Sheffield, Manchester, Leeds, Bradford, Royal Brompton Lomdon, Nottingham and Leicester NHS hospitals.
 
Description MRC Review of Positron Emission Tomography (PET) within The Medical Imaging Research Landscape
Geographic Reach National 
Policy Influence Type Participation in a national consultation
URL https://mrc.ukri.org/publications/browse/review-of-pet-within-the-medical-imaging-landscape/
 
Description Computational imaging assessment of pulmonary haemodynamics for non-invasive diagnosis of patients with pulmonary hypertension
Amount £15,715 (GBP)
Organisation Sheffield Hospitals Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2015 
End 09/2015
 
Description Developing an intelligent tool to improve prognostic and treatment response assessment on cardiac MRI data with machine learning
Amount £500,539 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2019 
End 06/2021
 
Description Development and application of multi-modality image processing methods for quantitative structural and functional understanding of lung diseases
Amount £200,000 (GBP)
Organisation GlaxoSmithKline (GSK) 
Sector Private
Country Global
Start 10/2018 
End 09/2020
 
Description Donald Heath Fellowships-Actelion funding
Amount £0 (GBP)
Organisation Actelion Pharmaceuticals Ltd 
Sector Private
Country United Kingdom
Start 10/2015 
End 09/2020
 
Description ECMC Renewal Application
Amount £100,997 (GBP)
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
End 03/2022
 
Description EU/ERS RESPIRE3 Marie Sklodowska-Curie COFUND Postdoctoral Global Research Fellowship
Amount £208,000 (GBP)
Organisation Marie Sklodowska-Curie Actions 
Sector Charity/Non Profit
Country Global
Start  
 
Description Evaluation of the microstructure and functional changes in the lung before and after major abdominal surgery, anaesthesia and mechanical ventilation, using functional hyperpolarised helium and xenon MRI
Amount £18,980 (GBP)
Organisation Association of Anaesthetists of Great Britain and Ireland (AAGBI) 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2017 
End 12/2017
 
Description Free-breathing, Rapid, Multi-nuclear MRI of lung structurefunction in infants
Amount £241,429 (GBP)
Organisation European Commission H2020 
Sector Public
Country Belgium
Start 08/2019 
End 08/2022
 
Description ICA Programme Clinical Doctoral Research Fellowship-Laurie Smith
Amount £0 (GBP)
Funding ID ICA-CDRF-2015-01-027 
Organisation National Institute for Health Research 
Department NIHR Biomedical Research Centre
Sector Public
Country United Kingdom
Start 05/2016 
End 04/2019
 
Description Image-guided radiotherapy
Amount £97,389 (GBP)
Organisation Sheffield Hospitals Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
End 04/2019
 
Description MICA: Non-invasive quantitative ventilation imaging by MRI of fluorocarbon gases
Amount £953,548 (GBP)
Funding ID MR/N018915/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2016 
End 12/2020
 
Description MRC
Amount £998,946 (GBP)
Funding ID MR/M008894/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2015 
End 03/2023
 
Description MRC Proposal - Sheffield and Newcastle
Amount £216,556 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2016 
End 03/2019
 
Description MRC Proposal-Sheffield and Newcastle
Amount £0 (GBP)
Funding ID MR/N018915/1 
Organisation Medical Research Council (MRC) 
Department MRC Human Nutrition Research Group
Sector Academic/University
Country United Kingdom
Start 04/2016 
End 03/2019
 
Description MSKCC costing for Research Component
Amount £22,760 (GBP)
Organisation Memorial Sloan Kettering Cancer Center 
Sector Academic/University
Country United States
Start 02/2018 
End 06/2018
 
Description Recovery and reuse of 129Xe in hyperpolarised MRI
Amount £113,422 (GBP)
Organisation Linde Group 
Sector Private
Country Global
Start 06/2016 
End 05/2024
 
Description Repeatibility of magnetic resonance imaging cardiopulmonary metrics in pulmonary arterial hypertension-implications for trial design
Amount £239,067 (GBP)
Funding ID GLAXOSMITHKLINE 
Organisation GlaxoSmithKline (GSK) 
Sector Private
Country Global
Start 01/2015 
End 01/2017
 
Description Research Radiographer
Amount £90,000 (GBP)
Funding ID L.GB.09.2014.7802 
Organisation Bayer 
Sector Private
Country Germany
Start 04/2015 
End 03/2018
 
Description Research grant form Boehringer-Ingelheim. 'Assessment of structural and functional lung MR imaging in the monitoring of treatment in IPF
Amount £250,000 (GBP)
Organisation Boehringer Ingelheim 
Sector Private
Country Germany
Start  
 
Description Respiratory Health in Preterm Neonates (RHINO)
Amount £80,028 (GBP)
Funding ID MR/M022552/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2017 
End 08/2019
 
Description Standardised ventilation perfusion and structure (VIPS) MRI platform for monitoring cystic fibrosis lung disease
Amount £93,759 (GBP)
Organisation Cystic Fibrosis Foundation 
Sector Charity/Non Profit
Country United States
Start 09/2017 
End 02/2019
 
Description TRISTAN V3
Amount £761,496 (GBP)
Organisation European Commission H2020 
Sector Public
Country Belgium
Start 01/2017 
End 12/2021
 
Description Towards functional lung imaging for MR-Linac based image-guided radiotherapy
Amount £3,999,800 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 12/2017 
End 11/2018
 
Description Validation of a non-invasive magnetic resonance image based computational tool for the diagnosis of PH.
Amount £48,028 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2017 
End 05/2018
 
Description Wellcome Trust - Clinical Research Training Fellowship. Pulmonary Vascular Disease: Computational Modelling and large data analytics
Amount £827,821 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 01/2022
 
Description Whole heart, four-dimensional flow magnetic resonance imaging for accurate assessment of right and left heart flow haemodynamics
Amount £25,400 (GBP)
Funding ID SGL018\1100 
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2018 
End 06/2019
 
Description Xenon-129 brain coil for 3T
Amount £20,000 (GBP)
Organisation Department of Health (DH) 
Sector Public
Country United Kingdom
Start 11/2018 
End 03/2019
 
Description Yorkshire Cancer Research (YCR) Catalyst for Innovation in Cancer Care and Treatment in Sheffield (YCR CONNECTS)
Amount £4,549,817 (GBP)
Organisation Yorkshire Cancer Research 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
End 03/2022
 
Description Yorkshire Cancer Research. 'Lung MRI for risk stratification to select non-small cell lung cancer patients for radical treatment
Amount £348,000 (GBP)
Organisation Yorkshire Cancer Research 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Title Portable xenon polariser 
Description Development of a portable xenon polariser that can be taken to novice sites waiting to access the technology for clinical lung imaging 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact Lung images acquired with xenon at papworth hospital Build of a polariser for UCL BRC 
 
Description CHANGE-MRI 
Organisation Hannover Medical School
Department Radiology Centre
Country Germany 
Sector Academic/University 
PI Contribution Definition and implementation of a multi site clinical evaluation of MRI perfusion imaging for screening of Chronic Thromboembolic Lung Disease
Collaborator Contribution Sole UK partner - acquisition of imaging data and methodology development
Impact None yet
Start Year 2016
 
Description Collaboration with GE Healthcare on developing 129Xe MRI hardware on new 1/5T scanner 
Organisation GE Healthcare Life Sciences
Country United Kingdom 
Sector Private 
PI Contribution Design, testing, iterative feedback and evaluation of new hardware for xenon MRI on new GE 1.5T MRI scanner
Collaborator Contribution Supply of base MRI system and multinuclear MRI hardware
Impact First 129Xe images at Sheffield Northern General Hospital acquired in 2017
Start Year 2013
 
Description Galapagos pharmaceuticals 
Organisation Galapagos NV
Country Belgium 
Sector Private 
PI Contribution Use of UoS 129Xe lung MRI as outcome measure in a clinical trial of an ILD drug
Collaborator Contribution Appended an imaging outcome measure sub study to an existing clinical trial of a new therapeutic for IPF - https://www.glpg.com/IPF
Impact None yet
Start Year 2019
 
Description RHINO 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution Our technology formed an essential component of the MRC award to Prof. Sailesh Kotecha for the RHINO (Respiratory Health Outcomes in Neonates) study. Pilot study from this study inidicates sub-clinical ventilation heterogeneity and microstructural differences in small airways of teenagers born pre-term.
Collaborator Contribution RHINO have recruited 40+ subjects that we have scanned in order for us to collect this data.
Impact N/A
Start Year 2017
 
Description Sloan Kettering, New York 
Organisation Memorial Sloan Kettering Cancer Center
Country United States 
Sector Academic/University 
PI Contribution Built RF coil for hyeperpolarised 13C breast MRI for group of Kayvan Kavani
Collaborator Contribution Provided definition of clinical need for new coil
Impact ISMRM abstract Draft paper to MRM Novel RF coil design IP owned by University of Sheffield
Start Year 2019
 
Description UCL NIHR BRC 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Build of a xenon polariser for UCL NIHR BRC
Collaborator Contribution Contract to build of a xenon polariser for UCL NIHR BRC
Impact NA yet
Start Year 2019
 
Description UK Pulmonary Hypertension MR imaging collaboration 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution I have been proactive in standardising and translating MRI protocols for pulmonary disease across all UK centres. I was asked by Prof Nick Morrell in Cambridge, to lead an imaging study with a standardised MR protocol based around the MRC funded national pulmonary arterial hypertension cohort study of which he is the PI. A cardio-pulmonary MR protocol has been drawn up and I am currently in the process of implementing this MR protocol in all of the UK PH clinical centres.
Collaborator Contribution Input on MR protocol design Patient recruitment
Impact Standardised UK Pulmonary Hypertension MRI protocol Basis for clinical trials of new therapies for PH with imaging outcomes
Start Year 2014
 
Description UK Pulmonary Hypertension MR imaging collaboration 
Organisation Newcastle University
Country United Kingdom 
Sector Academic/University 
PI Contribution I have been proactive in standardising and translating MRI protocols for pulmonary disease across all UK centres. I was asked by Prof Nick Morrell in Cambridge, to lead an imaging study with a standardised MR protocol based around the MRC funded national pulmonary arterial hypertension cohort study of which he is the PI. A cardio-pulmonary MR protocol has been drawn up and I am currently in the process of implementing this MR protocol in all of the UK PH clinical centres.
Collaborator Contribution Input on MR protocol design Patient recruitment
Impact Standardised UK Pulmonary Hypertension MRI protocol Basis for clinical trials of new therapies for PH with imaging outcomes
Start Year 2014
 
Description UK Pulmonary Hypertension MR imaging collaboration 
Organisation Papworth Hospital NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution I have been proactive in standardising and translating MRI protocols for pulmonary disease across all UK centres. I was asked by Prof Nick Morrell in Cambridge, to lead an imaging study with a standardised MR protocol based around the MRC funded national pulmonary arterial hypertension cohort study of which he is the PI. A cardio-pulmonary MR protocol has been drawn up and I am currently in the process of implementing this MR protocol in all of the UK PH clinical centres.
Collaborator Contribution Input on MR protocol design Patient recruitment
Impact Standardised UK Pulmonary Hypertension MRI protocol Basis for clinical trials of new therapies for PH with imaging outcomes
Start Year 2014
 
Description UK Pulmonary Hypertension MR imaging collaboration 
Organisation University of Cambridge
Department School of Clinical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution I have been proactive in standardising and translating MRI protocols for pulmonary disease across all UK centres. I was asked by Prof Nick Morrell in Cambridge, to lead an imaging study with a standardised MR protocol based around the MRC funded national pulmonary arterial hypertension cohort study of which he is the PI. A cardio-pulmonary MR protocol has been drawn up and I am currently in the process of implementing this MR protocol in all of the UK PH clinical centres.
Collaborator Contribution Input on MR protocol design Patient recruitment
Impact Standardised UK Pulmonary Hypertension MRI protocol Basis for clinical trials of new therapies for PH with imaging outcomes
Start Year 2014
 
Description UK Pulmonary Hypertension MR imaging collaboration 
Organisation University of Glasgow
Department School of Medicine Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution I have been proactive in standardising and translating MRI protocols for pulmonary disease across all UK centres. I was asked by Prof Nick Morrell in Cambridge, to lead an imaging study with a standardised MR protocol based around the MRC funded national pulmonary arterial hypertension cohort study of which he is the PI. A cardio-pulmonary MR protocol has been drawn up and I am currently in the process of implementing this MR protocol in all of the UK PH clinical centres.
Collaborator Contribution Input on MR protocol design Patient recruitment
Impact Standardised UK Pulmonary Hypertension MRI protocol Basis for clinical trials of new therapies for PH with imaging outcomes
Start Year 2014
 
Description Xenon MRI technology enabling 
Organisation Papworth Hospital NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Enabled xenon MRI technology at pap worth hospital
Collaborator Contribution Engineering expertise Xenon hyperppolarisation
Impact First xenon lung images acquired at pap worth
Start Year 2015
 
Description Xenon clinical trails consortium 
Organisation Cincinnati Children's Hospital Medical Center
Department Division of Rheumatology
Country United States 
Sector Hospitals 
PI Contribution Founding member of consortium for development , evaluation and standardisation of imaging methods for outcome measures for clinical trials of respiratory therapeutics
Collaborator Contribution evaluation and standardisation of imaging methods for outcome measures for clinical trials of respiratory therapeutic
Impact none yet
Start Year 2015
 
Title Clinical trial of Novartis treatment for COPD using hyper polarise lung MRI as primary outcome measure - Indacaterol/Glycopyrronium on Ventilation and Perfusion in COPD: A Randomized Trial 
Description The long-acting ß2-agonist/long-acting muscarinic antagonist (LABA/LAMA) combination indacaterol/glycopyrronium (IND/GLY) elicits bronchodilation, improves symptoms, and reduces exacerbations in COPD. COPD is classically associated with gas exchange impairment. Reduced ventilation, especially to perfused lung regions, may be further decreased during exacerbations, and has also been suggested to be related to disease severity. Ventilation defect is a key driver of impaired gas exchange, which can lead to impaired exercise tolerance, reduced quality of life, and death. The combined effect of a For Review Only LABA/LAMA on regional lung ventilation has not been assessed using hyperpolarized gas magnetic resonance imaging (MRI) before. What This Study Adds to the Field: This study shows for the first time, the positive effect of IND/GLY on ventilated lung volume in COPD using hyperpolarized gas MRI. Furthermore, improvements in ventilation leading to reduced ventilation/perfusion (V/Q) mismatch determined from MRI and accompanied by a trend towards increased diffusing capacity for carbon monoxide suggests that intervention with IND/GLY increases ventilation, improves V/Q ratio, and improves oxygenation. This could be an underlying pharmacodynamic mechanism that helps explain how IND/GLY reduces COPD symptoms and reduces the risk of exacerbations 
Type Diagnostic Tool - Imaging
Current Stage Of Development Small-scale adoption
Year Development Stage Completed 2017
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Demonstrated that a multi centre clinical trial of a respiratory therapeutic can be performed with high sensitivity lung imaging outcome measures performed in a single centre 
URL https://clinicaltrials.gov/show/NCT02634983
 
Title Hyperpolarised gas MRI 
Description NIHR, EPSRC, MRC 
Type Diagnostic Tool - Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2014
Development Status Under active development/distribution
Clinical Trial? Yes
Impact iMPORVED DETECTION OF LUNG DISEASE WITH A SENSITIVE NEW LUNG IMAGING MODALITY 
 
Title Sheffield lung imaging toolkit 
Description Graphic use interface for qualitative lung imaging 
Type Of Technology Software 
Year Produced 2016 
Open Source License? Yes  
Impact Transfer to sites in Newcastle and Columbia university New York 
 
Description British chapter ISMRM meeting 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact British chapter ISMRM meeting 2019
Year(s) Of Engagement Activity 2019
 
Description Deputy Editor of Journal of Magnetic Resonance Imaging 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Deputy Editor of Journal of Magnetic Resonance Imaging.
Year(s) Of Engagement Activity 2018
 
Description ISMRM workshop on value 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact ISMRM workshop on value 2019
Year(s) Of Engagement Activity 2019
 
Description Invited talk to NIHR academic on collaborating with industry 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited talk to NIHR academic on collaborating with industry
Year(s) Of Engagement Activity 2019
 
Description Member of Fleischner society, white paper writitng committee on PH imaging 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Member of Fleischner society, white paper writitng committee on PH imaging
Year(s) Of Engagement Activity 2018
 
Description PING 2017 meeting in Utah 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact PING 2017 meeting in Utah
Year(s) Of Engagement Activity 2017
URL http://www.physics.utah.edu/ping/
 
Description Plenary lecture Euromar 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary lecture at European Magnetic Resonance meeting in Krakow 2017
Year(s) Of Engagement Activity 2017
 
Description Plenary lecture ISMRM 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary lecture on xenon MRI at ISMRM meeting
Year(s) Of Engagement Activity 2016
 
Description Upenn lung imaging meeting 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Upenn lung imaging meeting 2019
Year(s) Of Engagement Activity 2019
URL https://www.med.upenn.edu/fmig-workshop-lung/
 
Description plenary talks at British Thoracic Society 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact plenary talks at British Thoracic Society 2019
Year(s) Of Engagement Activity 2019