Development of clinically viable, calibrated FMRI
Lead Research Organisation:
University of Oxford
Department Name: Clinical Neurosciences
Abstract
Magnetic resonance imaging (MRI) can be used to view the brain working; this is called functional MRI (or FMRI). By imaging the brain during its normal baseline state and then comparing that with images obtained during an active state (such as during a task like tapping your fingers or viewing flashing lights) we can see regional changes in blood flow and oxygen use which correspond to the areas which have increased metabolism during any given activity. Currently the images produced by this method tend to give locations which are statistically likely to be used, but they provide no information about the underlying metabolic activity which causes these changes in blood flow. Recently, models have been developed which try to extrapolate from what we can measure to estimate an actual metabolic rate of oxygen consumption. To accurately measure the severity and extent of acquired brain injuries such as stroke we mean to develop improved models and measurements of cerebral metabolism based on MRI data obtained from healthy human subjects. We wish to create a MRI-based method of measuring metabolic activity in the brain which is simple, fast and easy to use so that it can be employed in hospitals and emergency rooms throughout the country.
Publications
Blockley NP
(2017)
Rapid cerebrovascular reactivity mapping: Enabling vascular reactivity information to be routinely acquired.
in NeuroImage
Blockley NP
(2015)
Sources of systematic error in calibrated BOLD based mapping of baseline oxygen extraction fraction.
in NeuroImage
Bluemke E
(2020)
Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma.
in Clinical and translational radiation oncology
Bright MG
(2019)
Multiparametric measurement of cerebral physiology using calibrated fMRI.
in NeuroImage
Bright MG
(2011)
The effect of basal vasodilation on hypercapnic and hypocapnic reactivity measured using magnetic resonance imaging.
in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Bright MG
(2009)
Characterization of regional heterogeneity in cerebrovascular reactivity dynamics using novel hypocapnia task and BOLD fMRI.
in NeuroImage
Bulte D
(2016)
Hyperoxia and Functional MRI.
in Advances in experimental medicine and biology
Bulte D
(2017)
Monitoring cardiac and respiratory physiology during FMRI.
in NeuroImage
| Description | The key finding has been the creation of 2 new MRI techniques that produces quantitative images of a multitude of fundamental physiological parameters in the human brain in under 20 minutes using patient-friendly methods. The technique is comparable to oxygen PET but much faster, at a fraction of the cost, much greater availability to patients, and uses no ionising radiation. |
| Exploitation Route | The technique has been designed to be used with patients in hospitals. It will potentially be useful in a wide range of neuroimaging for a number of different diseases and injuries. The technique is to be trialled at the John Radcliffe Hospital in Oxford on carefully selected patients in a research setting. It will also be trialled at the Addenbrooks hospital in Cambridge. If these prove successful then it will be disseminated to other hospitals around the country. The technique also has potential benefit in academic neuroscience research and will be shared with colleagues in other universities around the UK and Europe. |
| Sectors | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | The MRI techniques developed in this project have enabled the non-invasive measurement of multiple aspects of cerebral physiology using MRI scanners. The techniques have been used both by other researchers around the world, and by colleagues at Oxford. We have already published a paper showing a correlation between one of these parameters and an early biomarker of Alzheimer's disease. |
| First Year Of Impact | 2012 |
| Sector | Education,Healthcare |
| Impact Types | Societal |
| Description | New Directions for EPSRC Research Leaders initiative |
| Amount | £261,498 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2012 |
| End | 09/2014 |
| Title | Respiratory Calibrated MRI |
| Description | Two respiratory calibrated MRI sequences and protocols capable of measuring a range of cerebral physiological parameters including blood flow, oxygen extraction and cerebral metabolic rate of oxygen. |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2013 |
| Provided To Others? | Yes |
| Impact | The techniques have been shared with researchers at the University of Cambridge, and Cardiff University. |
| Title | Oxygen metabolism model for MRI |
| Description | A mathematical model for combining multimodal MRI imaging data to calculate quantitative images of cerebral blood flow, cerebral blood volume, oxygen extraction fraction, arterial arrival time and cerebral metabolic rate of oxygen. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2012 |
| Provided To Others? | Yes |
| Impact | 181 citations so far. This research contributed to the foundation of the ICP Network http://www.icp-network.org |
| URL | https://www.sciencedirect.com/science/article/pii/S1053811911014194 |
| Description | Comparison of calibrated Functional MRI and steady state 15Oxygen Positron Emission Tomography for quantitative measurement of cerebral physiology |
| Organisation | University of Cambridge |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Researchers from FMRIB in Oxford worked at WBIC in Cambridge to enable WBIC to perform gas calibrated FMRI scans, while using the WBIC PET facilities to validate the MRI method |
| Collaborator Contribution | The researchers from WBIC recruited and performed triple oxygen 15 PET scans on research volunteers for the validation study, they also analysed the data and are collaborating with writing papers from the results. |
| Impact | Analysis if imaging results and writing of subsequent papers is in progress. Collaboration is multi-disciplinary, and involves physicists, clinicians, radiographers, neuroscientists, computer scientists, mathematicians and statisticians. |
| Start Year | 2012 |
| Description | PVD study |
| Organisation | Oxford University Hospitals NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I designed an MRI protocol for measuring blood flow changes in the lower leg as a result of interventional vascular surgery for peripheral vascular disease patients. I loaned the study respiratory gas analysers (value ~£12,000), other respiratory hardware, and helped to acquire and analyse the data. |
| Collaborator Contribution | We obtained funding to cover the costs of the MRI scans from the Acute Vascular Imaging Centre at the John Radcliffe Hospital. The hospital collaborated closely to recruit subjects for the study and as imaging was performed immediately prior to and immediately after surgery they were essential to the research. This has been a powerful, direct test of the use of oxygen enhanced MRI in patients to measure blood volume. |
| Impact | Final data analysis is currently underway. The promising results will result in a joint larger grant application in the near future. |
| Start Year | 2016 |
| Title | Oxygen enhanced MRI for cancer imaging |
| Description | Using oxygen enhanced MRI to identify hypoxic regions within tumours. This had been shown in preclinical xenographs but we were one of the first sites in the world to use this in a clinical trial in humans. |
| Type | Diagnostic Tool - Imaging |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2020 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | The impact shown resulted in OE-MRI being incorporated into a second trial at Oxford which has recently completed and I am now collaborating with Imperial and Manchester on further oxygen enhanced imaging with cancer trials including https://ncita.org.uk |
| Title | Double Excitation (Dexi) pCASL MRI pulse sequence |
| Description | This is an MRI pulse sequence which was written by Hannah Hare for use with the project. It allows for the simultaneous measurement of cerebral blood flow and the fMRI BOLD signal, in an improved way to the previous dual-echo method. |
| Type Of Technology | New/Improved Technique/Technology |
| Year Produced | 2014 |
| Impact | The sequence has been shared with the Wolfson Brain Imaging Centre at the University of Cambridge, and with colleagues at the University of Heidelberg in Germany. |
| Description | Brain-imaging technique could offer invaluable prognostic data |
| 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 | I was interviewed for an article in The Engineer about my new MRI technique. None noted |
| Year(s) Of Engagement Activity | 2012 |
| URL | http://www.theengineer.co.uk/sectors/medical-and-healthcare/news/brain-imaging-technique-could-offer... |
| Description | Getting the measure of MRI |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | My research was featured on the University of Oxford Science Blog. I was directly contacted by media outlets to be interviewed about my research, which resulted in mainstream media publications. |
| Year(s) Of Engagement Activity | 2012 |
| URL | http://www.ox.ac.uk/media/science_blog/120213.html |
| Description | ISMRM Education Committee |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Appointed to the Education Committee of the International Society for Magnetic Resonance in Medicine. . Awarding Body - ISMRM, Name of Scheme - Education Committee Aspects of physiological MRI were included in the educational syllabus to the society. |
| Year(s) Of Engagement Activity | 2013 |
| Description | Magnetic Resonance Imaging Explained |
| 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 | I was asked to create an online video explaining the basics of how MRI works for new students, which was then uploaded to Youtube for the general public to view. To date (Feb 2016) it has been viewed in excess of 118,000 times. The video has been viewed over 65,000 times and I have been told by international colleagues that they direct all new students to it in order to learn the basics of MRI. |
| Year(s) Of Engagement Activity | 2011 |
| URL | http://www.youtube.com/watch?v=MiL0wCZr0Mw |