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.
Organisations
- University of Nottingham, United Kingdom (Lead Research Organisation)
- University of Oxford, United Kingdom (Collaboration)
- University Hospitals of Leicester NHS, United Kingdom (Collaboration)
- University College London, United Kingdom (Collaboration)
- University of Gothenburg, Sweden (Collaboration)
- University of California, San Francisco, United States (Collaboration)
- University of Sydney, Australia (Collaboration)
- State University of Campinas (Collaboration)
- Newcastle University, United Kingdom (Collaboration)
- University of Birmingham, United Kingdom (Collaboration)
- Universidade de São Paulo (Collaboration)
- University of Cambridge (Collaboration)
- Wellcome Trust, LONDON (Collaboration)
- Basque Center on Cognition, Brain and Language (Collaboration)
- University of Chieti Pescara, Italy (Collaboration)
Publications

Al-Radaideh AM
(2013)
Increased iron accumulation occurs in the earliest stages of demyelinating disease: an ultra-high field susceptibility mapping study in Clinically Isolated Syndrome.
in Multiple sclerosis (Houndmills, Basingstoke, England)

Allan TW
(2015)
Functional Connectivity in MRI Is Driven by Spontaneous BOLD Events.
in PloS one

Antunes A
(2012)
Magnetic field effects on the vestibular system: calculation of the pressure on the cupula due to ionic current-induced Lorentz force.
in Physics in medicine and biology

Balla DZ
(2014)
Functional quantitative susceptibility mapping (fQSM).
in NeuroImage

Bandettini PA
(2012)
Ultrahigh field systems and applications at 7 T and beyond: progress, pitfalls, and potential.
in Magnetic resonance in medicine

Barnes GR
(2011)
Controlling false positive rates in mass-multivariate tests for electromagnetic responses.
in NeuroImage

Barratt EL
(2017)
Abnormal task driven neural oscillations in multiple sclerosis: A visuomotor MEG study.
in Human brain mapping

Barratt EL
(2018)
Mapping the topological organisation of beta oscillations in motor cortex using MEG.
in NeuroImage

Bawden S
(2017)
Increased liver fat and glycogen stores after consumption of high versus low glycaemic index food: A randomized crossover study.
in Diabetes, obesity & metabolism

Bawden SJ
(2016)
Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: A (31)P MRS study.
in Clinical nutrition (Edinburgh, Scotland)
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 |
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 | Public |
Country | United Kingdom |
Start | 03/2015 |
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 |
Start | 01/2012 |
End | 06/2015 |
Description | Experimental Medical Challenge Grant |
Amount | £4,200,000 (GBP) |
Funding ID | MR/K020803/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
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 | Public |
Country | United Kingdom |
Start | 06/2012 |
End | 06/2014 |
Description | Experimental Medicine for Mental Health |
Amount | £414,574 (GBP) |
Funding ID | MR/J01186X/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2012 |
End | 06/2014 |
Description | Leverhulme Trust Early career fellowship |
Amount | £150,000 (GBP) |
Organisation | The Leverhulme Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2010 |
End | 09/2013 |
Description | Leverhulme Trust Project Grant |
Amount | £26,500 (GBP) |
Organisation | The Leverhulme Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2015 |
End | 06/2018 |
Description | MRC Project grant |
Amount | £691,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2015 |
End | 09/2018 |
Description | New Investigator Research Grant |
Amount | £609,781 (GBP) |
Funding ID | MR/M006301/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
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) |
Funding ID | HD087202-01 |
Organisation | National Institute for Health Research |
Department | NIHR Biomedical Research Centre |
Sector | Public |
Country | United Kingdom |
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 | Public |
Country | United Kingdom |
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 | Leicester General Hospital |
Country | United Kingdom |
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 | State University of Campinas |
Country | Brazil |
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 | Universidade de São Paulo |
Department | Physics Institute of São Carlos |
Country | Brazil |
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 | Australia |
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 |
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 | University of California, San Francisco |
Department | Biomagnetic Imaging Laboratory (BIL) |
Country | United States |
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 |
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 |
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 |
Country | Spain |
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 | Wellcome Trust |
Department | Wellcome Trust Cente for Neuroimaging |
Country | United Kingdom |
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 |
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 |
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 |
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 |
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 |
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 | Yoursy |
Organisation | University College London |
Department | Institute of Neurology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | High field MRI expertise, MR physics |
Collaborator Contribution | Posing the question, interpreting the images, MR physics |
Impact | None yet |
Start Year | 2012 |
Description | fMRI applications - Birmingham |
Organisation | University of Birmingham |
Department | School of Psychology Birmingham |
Country | United Kingdom |
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 |
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 |
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/politicians |
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 |