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(BBSRC DTP) Dynamic Contrast-enhanced MRI: robust measurements of blood-brain-barrier leakage


Faculty of Biology, Medicine and Health

About the Project

Magnetic Resonance Imaging (MRI) can produce exquisite pictures of the brain. It is used to diagnose a variety of neurological diseases. Current work is transforming this technology from a machine that takes pictures into a measurement device that can take precise and accurate measurements of brain physiology. This can reveal age-related changes in the brain that are not immediately visible from looking at the picture (e.g. see Montagne et al, 2016).

One such approach is to inject contrast agent into the blood and to track its progress through the brain with dynamic MRI. In certain disease such as stroke, as well as in normal ageing, the blood vessel walls, forming the so-called ‘blood-brain barrier’, become leaky and harmful substances can enter the brain. We can detect where this is happening with dynamic contrast-enhanced MRI because the MRI signal changes as the contrast agent leaks out of the blood. There is a lot of current interest in cases of very subtle long-term leakage of the blood-brain barrier where it is thought this might cause damage to the brain cells, contributing to loss of cognitive function and ultimately dementia (Nation et al, 2019).

We can build computational physics-based models describing how the MRI signal changes over time as the contrast agent moves from the blood compartment into the brain tissue compartment. We fit these models to the dynamic MRI data from each pixel in the brain image to produce a quantitative map of the degree of leakage throughout the brain (O’Connor et al, 2011).

In this PhD project you will test different acquisition approaches to detect very low levels of contrast agent leakage. You will use a mixture of computer simulations, measurements in ‘phantoms’ (physical models, e.g. two compartments separated by a semi-permeable membrane) and measurements in the brains of healthy volunteers and in patients after a stroke. You will also test different analysis models to improve the accuracy of leakage estimation. Initially, existing images from 40 patients after an intra-cerebral haemorrhage will be used.

The ideal candidate will have a physics/engineering degree with a keen interest in biology and the brain. Research experience in imaging would be great but not essential. The successful student will gain training in MRI acquisition and analysis, computer programming and modelling. They will join a growing number of methods-oriented PhD students within the Division of Neuroscience and Experimental Psychology. The student will attend weekly lab meetings with our highly multidisciplinary team of scientists including physicists, mathematicians, biologists and neurologists and will benefit from a regular seminar program.

https://www.research.manchester.ac.uk/portal/en/researchers/laura-parkes(4fc9d6b6-a245-40a8-ab6d-cea04f34b65d).html

https://www.research.manchester.ac.uk/portal/en/researchers/adrian-parryjones(8ef609da-f27e-45a3-9eff-fe874db190f1).html

https://sites.manchester.ac.uk/mcrneuroim/

Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website http://www.manchester.ac.uk/bbsrcdtpstudentships

Funding Notes

Funding will cover UK tuition fees/stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website View Website

References

Montagne A, Nation DA, Pa J, Sweeney MD, Toga AW, Zlokovic BV, ‘Brain imaging of neurovascular dysfunction in Alzheimer’s disease’, Acta Neuropathol. 2016 May ; 131(5): 687–707. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283382/pdf/nihms836226.pdf

Nation DA, Sweeney MD, Montagne A, Sagare AP, D’Orazio LM, Pachicano M, Sepehrband F, Nelson AR, Buennagel DP, Harrington MG, Benzinger TLS, Fagan AM, Ringman JM, Schneider LS, Morris JC, Chui HC, Law M, Toga AW, Zlokovic BV, ‘Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction’, Nat Med. 2019 Feb;25(2):270-276. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367058/pdf/nihms-1511919.pdf

O’Connor JPB, Tofts PS, Miles KA, Parkes LM, Thompson G, Jackson A, ‘Dynamic contrast-enhanced imaging techniques: CT and MRI’ Br J Radiol 84(2) S112-S120, Dec [2011].
https://www.birpublications.org/doi/pdfplus/10.1259/bjr/55166688

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