Realising the benefits of structural and functional MRI at ultra-high-field

Lead Research Organisation: University of Nottingham
Department Name: Sch of Physics & Astronomy

Abstract

The quality of Magnetic Resonance Imaging (MRI) improves as the field strength of the scanner increases. Most hospitals in the UK have 1.5T scanners, but at the Sir Peter Mansfield Magnetic Resonance Centre in Nottingham we are exploring the potential of a 7T MRI scanner, currently the only one of its kind in the UK. We have already shown that this system gives significantly better quality pictures of the brain, and this will be further improved by the new hardware and software we plan to develop. This should enable us to find the ?missing lesions? in multiple sclerosis and to study changes in the brain associated with a range of neurodegenerative diseases, including Parkinson?s disease. We will validate some of the methodology using post mortem specimens, and then transfer it to patients. This will quickly lead to improved diagnosis and eventually to improved treatment. Ultra-high-field (7T) is particularly benefitial when MRI is used to study brain function. We will develop techniques for quantifying brain activity, and will combine images from MRI with data from other imaging methods, to identify networks of brain activity. Once developed, these techniques will provide a safe, non-invasive way for neuroscientists to explore and understand brain function, which remains one of our greatest scientific challenges. In Nottingham we will use these techniques to understand what the brain is doing when it is apparently resting, and how sequences of movement are learnt. We will also use them us to understand better the origins of some mental health problems. For example we will explore what happens when the brain fails to recruit a brain network appropriately, which is thought be the cause of inappropriate behavioural responses in Tourette?s syndrome, as well as some of the clinical symptoms of schizophrenia. Although our research involves leading edge facilities that are unlikely to become widely available in the near future, we anticipate that we will be able to find ways to transfer the most clinically promising methods to the lower field MRI systems that are to be found in almost every hospital in the UK.

Technical Summary

Ultra-high-field has delivered the expected improvement in sensitivity which we have exploited to increase the spatial resolution of structural and functional MRI (fMRI). In structural imaging, we are now fast approaching a resolution limit set by subject movement, which we aim to overcome by developing a motion tracking system. The limited performance of whole-body gradient systems poses a further restriction on achievable resolution. We will therefore exploit the potential of a novel insert gradient coil set to produce higher gradients at the threshold for peripheral nerve stimulation. Static (B0) and radiofrequency (B1) magnetic field inhomogeneities remain significant challenges at 7T; we will develop new B0-shimming strategies and explore ?multiple transmit? and ?travelling wave approaches for achieving B1-uniformity. Susceptibility effects contribute to enhanced contrast at 7T, but can be difficult to interpret. We will therefore develop quantitative methods for susceptibility mapping and relate the resulting maps to tissue iron content. We will also develop chemical exchange saturation transfer (CEST) techniques as a measure of myelination. We will validate these techniques using post mortem specimens and use them in vivo, together with more conventional MR contrast parameters, to detect boundaries between functional domains, to distinguish between white matter ischaemic and MS lesions, improve detection of cortical MS lesions and to measure iron content in the subcortical nuclei of patients with Parkinson?s disease. The improved spatial resolution we aim to achieve for fMRI will allow us to investigate the fine-grained functional organisation of the auditory cortex and to probe columnar organisation in other sensory areas. We will also develop improved methods of measuring haemodynamic parameters and use these to refine methods of calibrating the BOLD response at 7T. In linearity studies we will compare cerebral metabolic rate of oxygen (CMRO2) derived from the BOLD signal and other haemodynamic parameters with 13C MRS measurements of energy metabolism. We will also compare them to measures of electrical activity (MEG and EEG). We have already established a close correlation between electromagnetic and MR measures; we now wish to examine this relationship across different frequency bands and, using 1H and 13C MRS, relate it to the levels and turnover of excitatory and inhibitory neurotransmitters. We will develop muti-modal (MEG/EEG and EEG/fMRI) methods for this purpose. These methods will also be used to distinguish between network models of motor learning, and to compare the ?salience? network between control subjects and schizophrenics in whom it may be deficient.

Publications


10 25 50
 
Description EPSRC Neurodegeneration Committee
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description ICNIRP Scientific Expert Group (SEG)
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
 
Description ICNIRP document on movement in static fields
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
Impact Change in international guidelines on movements in static fields.
 
Description BBSRC fMRI grant
Amount £538,000 (GBP)
Funding ID BB/L000458/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 02/2014 
End 02/2017
 
Description Clinical Research Capabilities and Technologies Initiative
Amount £7,712,000 (GBP)
Funding ID MR/MR009122/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 04/2015 
End 03/2016
 
Description Dr Hadwen Trust Project Grant
Amount £124,788 (GBP)
Organisation Dr Hadwen Trust (DHT) 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2012 
End 06/2015
 
Description Experimental Medical Challenge Grant
Amount £4,200,000 (GBP)
Funding ID MR/K020803 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2014 
End 01/2018
 
Description Experimental Medicine for Mental Health
Amount £414,574 (GBP)
Funding ID MR/J01186X/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 07/2012 
End 06/2014
 
Description Experimental Medicine for Mental Health
Amount £414,574 (GBP)
Funding ID MR/J01186X/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 07/2012 
End 06/2014
 
Description Leverhulme Trust Early career fellowship
Amount £150,000 (GBP)
Organisation The Leverhulme Trust 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2010 
End 09/2013
 
Description Leverhulme Trust Project Grant
Amount £26,500 (GBP)
Organisation The Leverhulme Trust 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 03/2015 
End 06/2018
 
Description MRC Project grant
Amount £691,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 09/2015 
End 09/2018
 
Description New Investigator Research Grant
Amount £609,781 (GBP)
Funding ID MR/M006301/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 01/2015 
End 01/2018
 
Description Structure and function of the placenta from implantation to delivery; a next generation MRI approach
Amount $3,444,001 (USD)
Organisation National Institute for Health Research (NIHR) 
Department NIHR/BRC
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start  
 
Description Understanding and reducing artefacts in simultaneously acquired EEG and fMRI data
Amount £339,179 (GBP)
Funding ID EP/J006823/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 02/2012 
End 07/2015
 
Title Data analysis techniques for MEG 
Description Source localisation, and connectivity algorithms for MEG 
Type Of Material Improvements to research infrastructure 
Year Produced 2010 
Provided To Others? Yes  
Impact Collaborative papers with other research groups 
 
Title Jove Video on Best current practice for obtaining high quality EEG data during simultaneous FMRI. 
Description We collaborated with Brain Products GmbH in producing a JoVe video publication describing best current practice for obtaining high quality EEG data during simultaneous FMRI. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2013 
Provided To Others? Yes  
Impact This video has been used by Brain Products (and others) in advising new users how to carry out combined EEG-fMRI safely and efficiently. 
URL https://www.jove.com/video/50283/best-current-practice-for-obtaining-high-quality-eeg-data-during
 
Description Alzheimers 
Organisation University Hospitals of Leicester NHS Trust
Department Leicester General Hospital
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Hospitals 
PI Contribution Ultrahigh field MRI, development of imaging biomarkers
Collaborator Contribution Recruitment of patients, clinical need
Impact None
Start Year 2012
 
Description CInAPCe 
Organisation Universidade Estadual de Campinas
Country Brazil, Federative Republic of 
Sector Academic/University 
PI Contribution A tripartite agreement between the Universities of Nottingham and Birmingham and FAPESP in support of collaboration in the field of functional MRI with members of CInAPCe
Collaborator Contribution See above
Impact Exchange visits between participating centres.
Start Year 2012
 
Description CInAPCe 
Organisation University of Sao Paulo
Department Physics Institute of São Carlos
Country Brazil, Federative Republic of 
Sector Academic/University 
PI Contribution A tripartite agreement between the Universities of Nottingham and Birmingham and FAPESP in support of collaboration in the field of functional MRI with members of CInAPCe
Collaborator Contribution See above
Impact Exchange visits between participating centres.
Start Year 2012
 
Description Carbon 13 MRI/S 
Organisation University of Newcastle
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Clinical use of Carbon 13 MRS
Collaborator Contribution Demonstration of Carbon 13 studies of glutathione metabolism as a measure of oxidative stress.
Impact Research ongoing.
Start Year 2014
 
Description EuroBiomag 
Organisation University of Chieti-Pescara
Department Department of Neuroscience and Imaging
Country Italy, Italian Republic 
Sector Academic/University 
PI Contribution Access to 7T technical developments
Collaborator Contribution Novel 7T studies of spin echo and resting state analysis
Impact Collaboration as part of the EuroBiomag consortium
Start Year 2012
 
Description Functional connectivity analysis 
Organisation Radiology and Biomedical Imaging at UCSF
Department Biomagnetic Imaging Laboratory (BIL)
Country United States of America 
Sector Academic/University 
PI Contribution Collaborative work resulted in novel methods for identifying motor network connectivity
Impact PubMed No 21352925
Start Year 2009
 
Description High resolution visual fMRI 
Organisation University of Oxford
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution development of fMRI acquisitions
Collaborator Contribution Visual stimuli and patients
Impact Abstract and paper submitted
Start Year 2012
 
Description Huntingdon's disease 
Organisation University of Cambridge
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Ultrahigh field MRI, development of imaging biomarkers
Collaborator Contribution Recruitment of patients, clinical need
Impact None
Start Year 2012
 
Description International Training Network 
Organisation Basque Center on Cognition, Brain and Language (BCBL)
Country Spain, Kingdom of 
Sector Academic/University 
PI Contribution Training in MR methodologies
Collaborator Contribution Training in use of MR methodologies in cognitive neuroscience
Impact Ongoing
Start Year 2015
 
Description Multivariate analysis of MEG data 
Organisation The Wellcome Trust Ltd
Department Wellcome Centre for Neuroimaging
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Contribution of ideas to novel mathematical algorithms for data processing Provided data for testing algorithms
Impact PubMed Nos 21352925 and 21396438
Start Year 2011
 
Description ONBI CDT 
Organisation University of Oxford
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Joint MRC/EPSRC CDT
Collaborator Contribution Joint training programme
Impact Students recruited
Start Year 2012
 
Description University of Oxford 
Organisation University of Oxford
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Developing 7T imaging sequences for imaging the hippocampus in moving patients
Collaborator Contribution Clinical and psychological aspects
Impact Abstracts to neuroscience, clinical and imaging meetings
Start Year 2011
 
Description Use of independent component analysis in MEG 
Organisation University of Oxford
Department Oxford Centre for Human Brain Activity (OHBA)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Work on MEG network analysis. Data collection, development of ICA based tools for data processing
Impact PubMed ID No 21930901
Start Year 2010
 
Description Use of independent component analysis in MEG 
Organisation University of Oxford
Department Oxford Centre for Human Brain Activity (OHBA)
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Work on MEG network analysis. Data collection, development of ICA based tools for data processing
Impact PubMed ID No 21930901
Start Year 2010
 
Description Visual fMRI Cambridge 
Organisation University of Cambridge
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Acquisition of 7T high resolution fMRI data
Collaborator Contribution Data analysis methods for 7T fMRI data
Impact Multi-disciplinary - psychology and physics. Paper under review
Start Year 2014
 
Description fMRI applications - Birmingham 
Organisation University of Birmingham
Department School of Psychology Birmingham
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Access to 7 T scanner, high resolution fMRI methods and analysis
Collaborator Contribution Novel visual paradigms
Impact Multi-disciplinary
Start Year 2011
 
Description microstimulation 
Organisation University of Gothenburg
Country Sweden, Kingdom of 
Sector Academic/University 
PI Contribution To develop combined microstimulation and fMRI at 7T
Collaborator Contribution Partners are experts in microstimulation
Impact ISMRM abstract sfN abstract
Start Year 2012
 
Description microstimulation 
Organisation University of Sydney
Country Australia, Commonwealth of 
Sector Academic/University 
PI Contribution To develop combined microstimulation and fMRI at 7T
Collaborator Contribution Partners are experts in microstimulation
Impact ISMRM abstract sfN abstract
Start Year 2012
 
Description BBC Radio Nottingham Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Public awareness of research conducted

N/A
Year(s) Of Engagement Activity 2011
 
Description Expo 2010, Shanghai 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Policymakers/parliamentarians
Results and Impact Whole day event attended by approximately 100 Chinese scientific and healthcare policy makers. Two lectures were delivered with lunchtime open discussions followed by post event discussions with individual representatives.

Invitations to deliver lectures at two laboratories of the Chinese National Academy of Sciences.
Year(s) Of Engagement Activity 2010
 
Description Get on 4 Uni 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact 30 academically gifted school pupils whose parents had not attended university visited the Sir Peter Mansfield MR Centre for a 40 minute talk followed by a demonstration of the imaging facilities (3T, 7T MRI and MEG).

Feedback from pupils was very positive.
Year(s) Of Engagement Activity 2011,2012,2013
 
Description Media coverage of Nigrosome paper 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact PAG Interviewed on local TV, NB interviewed on local radio, coverage in National Newspapers

Requests for further information from general public
Year(s) Of Engagement Activity 2013
 
Description Ningbo Science Academy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact About 100 people attended to find out more about MRI.

Visit to a hospital in Ningbo and meeting radiographers there.
Year(s) Of Engagement Activity 2011
 
Description Public open day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Open day as part of national science week or University Community Open Day (in later years)

Improved public understanding of science
Year(s) Of Engagement Activity 2011,2012,2013,2014
 
Description Radio interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Radio 4 interview given as part of a series on 'Images that changed the world'.

Positive feedback from general public.
Year(s) Of Engagement Activity 2010
 
Description School visits 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Schools
Results and Impact A number of visits to schools throughout the year

Increased interest in science
Year(s) Of Engagement Activity 2010,2011,2012,2013
 
Description sixty symbols 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact 20,000 people have watched a video on MRI

Enhanced public understanding
Year(s) Of Engagement Activity 2010,2011,2012,2013