Water exchange in the vasculature of the brain (WEX-BRAIN)
Lead Research Organisation:
University College London
Department Name: Computer Science
Abstract
The blood-brain barrier separates blood vessels from brain tissue. It allows molecules critical to normal brain function to pass but blocks other, potentially toxic, molecules. Such toxic substances can pass into the brain when the blood-brain barrier if not functioning correctly. Abnormal blood-brain barrier function is associated with many brain conditions (for example, stroke, dementia and multiple sclerosis) and is thought to play an important role in the development of these conditions. It is important to be able to measure blood-brain barrier function as this may help with diagnosis, developing therapies and monitoring treatment. Unfortunately, currently there are no non-invasive and reliable methods to do this. Within this project we plan to develop new ways to measure blood-brain barrier function by measuring how easily water passes across it. We will develop new advanced magnetic resonance imaging (MRI) scanning and computer-based analysis to generate images that tell us how leaky the blood-brain barrier is. We will test these measurements using computational simulations and animal measurements. We will then apply these measurements in a small set of human volunteers and patients in order to demonstrate that these methods can detect blood brain barrier abnormalities and can do so in a clinical setting. The outcome of the project will be new tools to enable doctors to diagnose and treat patients with brain conditions more effectively.
Planned Impact
We anticipate short-term benefits to the academic community, scanner manufacturers and the pharmaceutical industry, with subsequent benefits for healthcare and patients. Biophysicists, imaging physicists and biomedical researchers are the initial WEX-BRAIN end-users, using our novel Blood-brain barrier (BBB) water exchange measurements to inspire further innovation and in mechanistic studies and clinical treatment trials. Clinicians will be longer-term end-users of this research, using BBB water exchange measurements to characterise disease early and select and monitor treatment on an individual basis. This should lead to earlier, effective intervention which is cost-effective, as it increases the time before the person starts drawing on health and social care services.
Publications
Al-Bachari S
(2020)
Blood-Brain Barrier Leakage Is Increased in Parkinson's Disease.
in Frontiers in physiology
Dickie B
(2020)
Measuring water exchange across the blood-brain barrier using MRI
in Progress in Nuclear Magnetic Resonance Spectroscopy
Dickie BR
(2022)
Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI.
in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Dickie BR
(2024)
A community-endorsed open-source lexicon for contrast agent-based perfusion MRI: A consensus guidelines report from the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).
in Magnetic resonance in medicine
Dickie BR
(2020)
Measuring water exchange across the blood-brain barrier using MRI.
in Progress in nuclear magnetic resonance spectroscopy
Elizabeth Powell
(2021)
Diffusion-filtered exchange measurements of blood-brain barrier permeability to water
Elizabeth Powell
(2021)
Blood-brain barrier water exchange estimation using optimised contrast-enhanced ASL
Harris WJ
(2023)
In vivo methods for imaging blood-brain barrier function and dysfunction.
in European journal of nuclear medicine and molecular imaging
Manning C
(2021)
Sources of systematic error in DCE-MRI estimation of low-level blood-brain barrier leakage.
in Magnetic resonance in medicine
| Description | - Diffusion MRI methods can be used to measure water exchange across the blood-brain barrier in the healthy brain. - Contrast-enhanced arterial spin labelling provides a potential alternative strategy for assessing subtle blow-brain barrier permeability to water. - Water exchange methods are sensitive to blood-brain barrier disruption caused by lung infection. |
| Exploitation Route | Application in a range of neurological diseases to probe subtle blood brain barrier involvement, potentially as an early marker of disease. |
| Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | We have been involved in a number of public engagement activities that have helped inform members of the public of the role that MRI plays in diagnosing neurological diseases. |
| First Year Of Impact | 2021 |
| Sector | Education |
| Impact Types | Societal |
| Description | BBB Water exchange in Camino: Pump-priming award from EPSRC platform grant EP/M020533/1 |
| Amount | £24,194 (GBP) |
| Organisation | University College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2021 |
| End | 06/2021 |
| Description | Blood-brain barrier dysfunction in post-stroke dementia |
| Amount | £552,808 (GBP) |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 01/2023 |
| Description | Imaging early blood-brain barrier dysfunction in dementia |
| Amount | £100,000 (GBP) |
| Funding ID | 2453618 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2020 |
| End | 03/2024 |
| Description | Lancaster University EPSRC Impact Acceleration Account & Lancashire Teaching Hospitals NHS Foundation Trust |
| Amount | £130,235 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2023 |
| End | 01/2026 |
| Description | Molecular imaging of neurodegenerative pathology using deuterium MRI (MINDER) |
| Amount | £179,542 (GBP) |
| Funding ID | BB/X004260/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2023 |
| End | 04/2024 |
| Description | Neurology Research Fellow |
| Amount | £178,000 (GBP) |
| Organisation | Lancaster University |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 07/2021 |
| End | 07/2024 |
| Description | Quantifying blood-brain barrier water exchange at 7 T |
| Amount | £7,500 (GBP) |
| Organisation | King's College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 06/2021 |
| End | 12/2021 |
| Description | Subtle blood-brain barrier dysfunction in MS: implementation and clinical application of a novel MRI technique |
| Amount | £49,929 (GBP) |
| Funding ID | 149 |
| Organisation | Multiple Sclerosis Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2023 |
| End | 12/2023 |
| Description | The Beat Goes On: imaging brain artery stiffness and the damage caused by poor buffering of pulsatile blood flow |
| Amount | £1,828,847 (GBP) |
| Funding ID | 224267/Z/21/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2022 |
| End | 05/2027 |
| Description | The impact of water exchange on measures of myocardial blood flow and extracellular volume by contrast-enhanced MRI |
| Amount | £203,700 (GBP) |
| Funding ID | PG/20/10008 |
| Organisation | British Heart Foundation (BHF) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 12/2024 |
| Description | Towards robust and sensitive MRI biomarkers of pericyte-mediated vascular dysfunction in dementia |
| Amount | £69,591 (GBP) |
| Organisation | Alzheimer's Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2023 |
| End | 05/2024 |
| Description | Understanding how the brain recovers from cerebral malaria |
| Amount | £529,919 (GBP) |
| Funding ID | MR/V034650/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2021 |
| End | 07/2024 |
| Description | Water Exchange in the Vasculature of the Brain (WEX-BRAIN) |
| Amount | £86,059 (GBP) |
| Funding ID | EP/S031375/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2019 |
| End | 10/2022 |
| Description | Water exchange in the vasculature of the brain (WEX-BRAIN) |
| Amount | £20,969 (GBP) |
| Funding ID | EP/S031332/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2019 |
| End | 10/2022 |
| Description | Water exchange in the vasculature of the brain (WEX-BRAIN) |
| Amount | £13,082 (GBP) |
| Funding ID | EP/S031367/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2019 |
| End | 07/2022 |
| Description | Wissenchaftkolleg Short Term fellow |
| Amount | £18,994 (GBP) |
| Organisation | Berlin Institute for Advanced Study |
| Sector | Academic/University |
| Country | Germany |
| Start | 08/2024 |
| End | 02/2025 |
| Title | Relaxation-time corrected FEXI method for blood brain barrier water exchange quantification |
| Description | Novel method based on the filter exchange imaging (FEXI) method. Uniquely our approach corrects for water relaxation times in calculation of water exchange rates using a 2-compartment model, allowing for more accurate estimates. This is deployed as a whole-brain multislice MRI imaging method. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | Improved quantification of water exchange, now being deployed in clinical studies of small vessel disease and multiple sclerosis. |
| URL | https://doi.org/10.1002/mrm.29616 |
| Description | International SVD Clinical Services Network |
| Organisation | University of Edinburgh |
| Department | Edinburgh Neuroscience |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Contribution to working group based on expertise in cerebral small vessel disease, including creation of core data set with the network members, review of papers, contribution of patient information leaflet on white matter lesions, etc. |
| Collaborator Contribution | As above |
| Impact | Core data set for standardisation of data collection in SVD clinic setting - in development Patient information - in development |
| Start Year | 2023 |
| Description | North West of England collaboration on cerebral small vessel disease. |
| Organisation | Salford Royal NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | WEX-BRAIN has catalysed a new collaboration on small vessel disease between the neuroscience centres in Lancashire and Greater Manchester. The addition of Salford Royal NHS Foundation Trust as a recruitment centre has led to joint working between Dr Sen (Greater Manchester), Prof Emsley (Lancashire Teaching Hospitals NHS Foundation Trust & Lancaster University) and Dr Maskery (Clinical Research Fellow, Lancaster University) on patient recruitment and SVD clinic collaboration. Collaborative abstracts describing SVD clinical services and burden have been submitted to the UK Association of British Neurologists Meeting 2023 and to the European Stroke Organisation Conference 2023. |
| Collaborator Contribution | Identification of research participants for the clinical WEX-BRAIN study New collaborative academic partnership Training opportunity through attendance of clinical research fellow at a dedicated SVD clinic in Manchester |
| Impact | Collaborative abstracts describing SVD clinical services and burden have been submitted to the UK Association of British Neurologists Meeting 2023 and to the European Stroke Organisation Conference 2023. |
| Start Year | 2022 |
| Description | The Beat Goes On: imaging brain artery stiffness and the damage caused by poor buffering of pulsatile blood flow |
| Organisation | Cardiff University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Water exchange measurements for probing damage to the blood-brain barrier associated with brain artery stiffness |
| Collaborator Contribution | New application area for water exchange measurements |
| Impact | None yet |
| Start Year | 2022 |
| Description | Water exchange measurements in Alzheimer's disease |
| Organisation | University College London |
| Department | Dementia Research Centre (DRC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Provision of expertise on water exchange measurements |
| Collaborator Contribution | Provision of expertise on Alzheimer's disease |
| Impact | None |
| Start Year | 2022 |
| Description | Water exchange measurements in multiple sclerosis |
| Organisation | University College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Contribution of methodological expertise on water exchange measurements based on those developed within the grant. |
| Collaborator Contribution | Funding and supervision for PhD studentship. |
| Impact | Collaboration is multidisciplinary, with physics and neurology input. |
| Start Year | 2019 |
| Title | Implementation of FEXI sequence on Connectom 300 mT/m MRI system |
| Description | This is implementation of the filtered exchange imaging (FEXI) sequence that is critical to the WEX-BRAIN project (EP/S031510/1). This sub-project to Cardiff was explicitly to implement the sequence on the Siemens Connectom scanner, one of just four in the world, with ultra-strong (300 mT/m) gradients. The sequence had to be built from basics and a working prototype has been created. This is still under evaluation in collaboration with the main WEX-BRAIN partners at UCL (EP/S031510/1) |
| Type Of Technology | New/Improved Technique/Technology |
| Year Produced | 2021 |
| Impact | None as yet - still under evaluation |
| Description | Bloomsbury Festival 2022 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | My group presented a range of exhibits to the general public over 2 days as part of the Bloomsbury Festival 'Breathe' Discovery Hub. Hundreds of members of the public attended, finding out about medical imaging. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://bloomsburyfestival.org.uk/2022-review/ |
| Description | Bloomsbury Festival stand |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Annual Bloomsbury Festival. Elizabeth Powell contributed to a stand showing the impact of medical imaging. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://stories.rosaproductions.co.uk/bloomsbury-festival-2023/index.html |
| Description | British Science Festival Award Lecture, winner for agricultural, biological and medical sciences. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | We are delighted to announce that Dr Yolanda Ohene, based at the University of Manchester, is the British Science Festival 2021 Award Lecture winner for agricultural, biological and medical sciences. Yolanda has been awarded this recognition for her fascinating research that explores our ability to see and understand what is going on inside the brain and how critical this is for the diagnosis and treatment of neurodegenerative illnesses, such as Alzheimer's disease. Yolanda has recorded a short video clip discussing her work here. In her talk at the British Science Festival in September, Yolanda will discuss how traditional techniques to observe the inner workings of our minds in a non-invasive and meaningful way, poses challenges for scientists and clinicians. She has used Magnetic Resonance Imaging (MRI) technology to develop new, ground-breaking techniques for getting inside the head. By visualising the way water molecules move through the blood vessels in the brain, she is bringing together biology and physics to revolutionise the way we approach brain health. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://britishsciencefestival.org/a-window-into-the-brain/ |
| Description | British Science Festival Award Lecture, winner for agricultural, biological and medical sciences. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | British Science Festival Award Lecture, winner for agricultural, biological and medical sciences. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://britishsciencefestival.org/a-window-into-the-brain/ |
| Description | Conference for undergraduate women in Physics 2021 - Intersectionality and Black Women in Physics |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Undergraduate students |
| Results and Impact | The CUWiP UK is aimed at undergraduates in physics and astronomy in the UK who identify as women, and is intended to empower and inspire delegates, giving them the confidence to express themselves and to pursue careers using their physics knowledge and skills. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://cuwip2021.soton.ac.uk |
| Description | IOP: Limitless School careers day - Physics in Medicine |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | IOP: Limitless School careers day - Physics in Medicine, Chair |
| Year(s) Of Engagement Activity | 2021 |
| URL | http://limitlesscareers.iopconfs.org/1019001 |
| Description | Imaging our insides |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | South Hampstead High School talk |
| Year(s) Of Engagement Activity | 2020 |
| Description | Lancaster Medical School research strategy event |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Around 40 attendees at an event to discuss Lancaster Medical School research strategy and the interface with regional NHS organisations. The attendees were drawn from a very mixed professional background linked to medical research and healthcare delivery, comprising a few clinicians, quite a few regional research directors/heads of R&D, senior research nurses, middle ranking and senior NHS managers and a couple of non-clinical university academics 10:00 Introduction 10:05 Opening remarks from Chief Executive of Lancashire Teaching Hospitals NHS Foundation Trust 10:10 A series of short presentations from Hedley Emsley and colleagues on examples of how clinical neuroscience research is facilitated in the region. This included a presentation from the clinical research fellow (and current PhD student) working on the WEX-BRAIN clinical study. 10:55 Comfort break 11:05 Q&A, discussion and idea sharing, to include: The long term strategic aims/desired outcomes of partnering across the region to facilitate clinical Neuroscience research What will enable us to engage and be successful? Next steps/quick wins? Please come to the day ready to share your thoughts on the above. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Limitless School careers day - Physics in Medicine |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | o celebrate National Careers Week (1-6 March 2021), teachers of students aged 12-14 across the UK and Ireland are invited to book their classes onto our programme of events exploring the opportunities that studying physics can unlock. This celebration is part of Limit Less, the new campaign from the Institute of Physics to support young people to change the world and fulfil their potential by doing physics. That's why, in National Careers Week, we want to show how studying physics can open the door to a vast range of careers that are creative, stimulating and relevant to the challenges facing us all as a society. Speakers taking part in Careers Week come from all over the world of physics, including research and industry, well-known organisations and innovative start-ups. During the events, your young people will hear about the diverse routes into these careers, including technical and vocational pathways, and the exciting possibilities that an apprenticeship could bring. |
| Year(s) Of Engagement Activity | 2021 |
| URL | http://limitlesscareers.iopconfs.org/1019001 |
| Description | Participation in the Bloomsbury Festival 2021 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | We hosted a large stand at the 2-day Bloomsbury Festival event on 22-23 October 2021. The stand included a range of items designed to present medical imaging and its relevance to a range of diseases and organs. The material was designed to appeal to a wide range of ages, and the stand was attended by primary and secondary school students, teachers, parents, and members of the general public of all ages. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://bloomsburyfestival.org.uk/2021-festival/ |
| Description | Royal Institution Masterclass - Looking into the Brain |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Royal Institution Masterclass - Looking into the Brain |
| Year(s) Of Engagement Activity | 2021 |
| Description | Update on SVD research in Lancashire |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Presentation to preclinical and clinical academic audience at a regional forum, with international representation (including visiting academics from a North American institute), on SVD. This was an update on SVD research activity in Lancashire, including WEX-BRAIN. |
| Year(s) Of Engagement Activity | 2023 |