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

10 25 50
 
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 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 08/2020 
End 03/2024
 
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 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 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 £800,509 (GBP)
Funding ID EP/S031510/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 11/2019 
End 11/2022
 
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 06/2019 
End 07/2022
 
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
 
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 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 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