Longitudinal assessment of healthy brain structure and function across the lifespan using 9.4T Magnetic Resonance Imaging

Lead Research Organisation: University of Edinburgh
Department Name: Centre for Cardiovascular Science

Abstract

Live Imaging of the human and animal brain, using Magnetic Resonance Imaging, has provided a wealth of information regarding the structural and functional properties of the brain across the lifespan, and identified markers associated with disease. Such specialised imaging modalities can also inform on the mechanisms and variance within populations across development and ageing. For this research to be world leading, the highest resolution scanners are required to provide accurate details of tissue structure and composition. We have an excellent, integrated infrastructure for human and animal brain imaging, but our old, animal MRI scanner needs to be replaced and upgraded, to allow us to see smaller changes in the brain structure, function, composition and connectivity and ensure our translational research remains world class.

Technical Summary

We seek part funding for an advanced, 9.4T MRI scanner and ancillary equipment central to the work of Edinburgh Neuroscience, incorporating newly emerging technology to remain at the international forefront of neuroimaging research that is informing our understanding of brain development, midlife risk factors and ageing in animal models.

The 9.4T MRI scanner will be equipped with high performance gradients, multinuclear capability and a range of head and body coils. Brain coils will increase resolution for high-resolution structural imaging (e.g. T1, T2, T2*, FLAIR) and wide-ranging specialist imaging techniques (diffusion tensor, perfusion, permeability and magnetisation transfer imaging, functional MRI, multinuclear spectroscopy, angiographic and flow quantification).

The 9.4T scanner will replace a 7T MRI scanner, which is outdated technology unsupported by the company. It no longer meets the high specifications needed to be internationally-leading in high resolution structural/functional imaging and spectroscopy. The new 9.4T scanner is essential to provide a comprehensive range of high resolution in vivo imaging for our programmes of work understanding healthy brain development and ageing; disease progression or resilience in response to environmental stress; and mechanistic understanding of molecular pathways crucial for healthy development and ageing in our rodent models.

Planned Impact

Magnetic Resonance Imaging (MRI) allows visualisation of brain size, integrity and function in humans, large animals and small animals. This is a non-invasive method that is invaluable to understand the brain as it changes through the lifecourse from development to ageing. At present we have an old, unreliable 7 Tesla MRI scanner and will replace it with a 9.4T MRI scanner. The proposed purchase of the 9.4T MRI scanner will significantly improve our preclinical small animal MRI service to academics, namely, increased reliability of service and enhanced imaging capabilities.

The enhanced imaging capabilities will enable novel advanced protocols to measure different aspects of the brain: its size, structural integrity and functional connectivity. MR physicists, biologists and image analysts will have the technology to develop novel methodology to acquire the images and analyse them.

The developmental and ageing biologists will have access to the novel methodology as users of the 9.4T MRI facility. This will enable longitudinal analysis of imaging markers of development and ageing in each animal and then determine the variance of these markers in a population. The impact of the high resolution imaging data combined with other neurotechnical approaches will generate an enhanced impact on the outcomes of the research, for example high impact publications and increased
numbers of successful grant applications involving high resolution Imaging.

The relevance to human and large animal health is unquestionable, as the population variance in developmental and ageing processes are translated from rodents to large animals and man.

Publications

10 25 50
 
Description The main objective of this grant was to purchase and install an upgrade of a 9.4T MRI in our Preclinical Imaging Facility. The new MRI scanner has now been installed and a wide dissemination of the importance and opportunities enabled by this new equipment to researchers across the University has been made. This upgraded MRI facility, partially funded by the BBSRC, will now enable cutting edge imaging of the live animal for our current users and encourage new researchers from across the University to incorporate MRI imaging as a powerful technique to facilitate their research.
Exploitation Route The 9.4T MRI scanner will allow high definition structural and functional scans of small animals. The imaging can be carried out on small animals of all ages, from fetus to old age. It can focus on whole body or follow the changes in structure of specific organs (eg. brain, heart, kidney) from fetus to old age, hence allowing a longitudinal analysis across the lifespan in normal animals and disease models. The high power of this imager enables very high resolution of the structure, but it also enables functional analysis - for example brain connectivity while carrying out specific tasks. The applicants of this grant have focussed on the brain structure and function across the lifespan but functional information on other organs, such as heart and kidney, will be investigated by other researchers in our MRI facility . The new MRI facility will be open to all researchers to advance their research goals.

Although the MRI scanner installation was delayed because of COVID, this award had a significant impact on the decision of Dr Axel Montagne to join the group of co-applicant Prof Giles Hardingham with Fellowship funding from the MRC (£1.5M). Furthermore, funding for using MRI to investigate blood-brain barrier integrity was obtained from the Rosetrees Trust. Therefore, this new equipment is already spurning new collaborations and research directions.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

URL https://www.ed.ac.uk/clinical-sciences/edinburgh-imaging/edinburgh-preclinical-imaging
 
Description Analysis of the role of endothelial autophagy in blood-brain barrier integrity by magnetic resonance imaging
Amount £9,408 (GBP)
Funding ID Seedcorn2021\100098 
Organisation Rosetrees Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2022 
End 03/2023
 
Description Interplay between brain endothelial cells and pericytes in brain
Amount £1,586,719 (GBP)
Funding ID MR/V032488/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2022 
End 12/2026
 
Description Small animal Magnetic Resonance Imaging of Lifecourse: from Developmental Diseases to Dementia
Amount £1,000,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2019 
End 06/2024
 
Description GEMRIC 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution Exchange of knowledge. Collaborated on project and project proposals for future research.
Collaborator Contribution Exchange of knowledge. Collaborated on project and project proposals for future research.
Impact publication: DOI 10.1371/journal.pone.0162545 DOI: 10.1136/heartjnl-2015-308734.16 DOI: 10.1136/heartjnl-2015-308066.170 DOI: 10.1016/j.mri.2016.10.013 BHF new horizons grant: Towards metabolic assessment of myocardial viability
Start Year 2008
 
Description Access facilities to drive innovation 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Explore the highly specialised expertise and facilities Edinburgh University has to offer academic colleagues and organisations to support your projects from bench to bedside. Discover how to get in touch directly for scientific questions or support via Edinburgh Innovations for pricing and contracting.
Year(s) Of Engagement Activity 2021
 
Description Roadshow to disseminate information on Preclinical Imaging 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact The roadshow highlights all of the new and existing preclinical imaging facilities to all interested researchers across the University. Special emphasis was made to provide a timeline for the introduction of the new MRI scanner and its capabilities
Year(s) Of Engagement Activity 2020
URL https://www.ed.ac.uk/clinical-sciences/edinburgh-imaging/edinburgh-preclinical-imaging/
 
Description Virtual Symposium on Update of Preclinical Imaging Facilities 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Preclinical Facilities update and opportunities for Research and Clinical staff at the University of Edinburgh.
Short talks about the 4 different preclinical imaging facilities, (MRI, PET/CT, Ultrasound and optical imaging) including the novel imaging opportunities generated by the new 9.4T MRI scanner. This led to increased interest in MRI imaging and new possibilities

You can join us on the day using the following link:
https://eu.bbcollab.com/guest/6a6d5a6612034a62a5f502697841860f
Year(s) Of Engagement Activity 2020
 
Description Website notification of arrival of new 9.4T MRI scanner 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The advertisment of the new BBSRC/WT funded MRI scanner will increase interest in using the scanner. Researchers could then plan for their new research studies involving the use of the scanner.
Year(s) Of Engagement Activity 2020
URL https://www.ed.ac.uk/clinical-sciences/edinburgh-imaging/edinburgh-preclinical-imaging/news/new-9-4t...