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Development of MRI markers of brain inflammation and application in traumatic brain injury


   Faculty of Biology, Medicine and Health

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  Dr A Greenhalgh, Dr L Parkes, Dr Hiren Patel  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

Manchester United Kingdom Biomedical Engineering Biophysics Immunology Medical Physics Neurology Neuroscience

About the Project

Neuroinflammation following brain injuries such as stroke and traumatic brain injury (TBI) is thought to be a key contributor to associated long-term problems, such as neurodegenerative disease, cognitive decline and dementia. Current neuroimaging tools do not adequately define neuroinflammation, therefore, there is an urgent need for improved techniques to understand the neuroinflammatory processes in the human brain.

Magnetic resonance imaging (MRI) can be used to image neuroinflammatory processes, such blood-brain barrier breakdown. For example, by injecting a contrast agent into the blood and tracking its progress through the brain we can build computational physics-based models describing how the brain MRI signal changes over time. Fitting these models to the dynamic MRI data allows us to estimate contrast agent leakage and produce quantitative brain images useful to clinicians.

In this PhD, we will address several important issues in this field.

We will improve the MRI acquisition approaches to increase our ability to rapidly detect very low levels of contrast agent in the brain. This will initially be performed using computer simulations and then by comparing different acquisition approaches in the brain of healthy volunteers. We will compare different analysis models and identify the most accurate method of quantifying and visualising regional blood-brain barrier breakdown.

We will evaluate other novel measurements of neuroinflammation, for example, ultra-small iron oxide particles that get taken up by circulating immune cells that then cross into the brain. We will test different MRI methods that are sensitive to the accumulation of iron oxide and use rodent models to optimise and validate these measurements.

Finally, a combination of these new and optimised measurements will be applied in patients with TBI to test their capability to identify hidden brain injury. The ability to visualise currently unseen injury would transform our understanding of neuroinflammation in brain injury. 

Entry Requirements:

Applicants are expected to hold (or about to obtain) a minimum upper second class undergraduate honours degree (or equivalent) in physics or engineering with a keen interest in biology and the brain. Research experience in imaging is desirable. 

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. You MUST also submit an online application form - choose PhD Biomedical Imaging Sciences.

Equality, Diversity & Inclusion

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 https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/ 


Funding Notes

This project is jointly funded by the University of Manchester and Philips Healthcare. Studentship funding is for a duration of three years to commence in September 2021 and covers UK tuition fees and a UKRI stipend (£15609 per annum 21/22). The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a scholarship that will enable full studentship to be awarded to international applicants. This full studentship will only be awarded to exceptional quality candidates, due to the competitive nature of this funding.

References

Daniel S. Albrecht, Cristina Granziera, Jacob M. Hooker, and Marco L. Loggia, ‘In vivo imaging of human neuroinflammation’, ACS Chem Neurosci: 2016, 7, 470-483.
Verboon LN, Patel HC, Greenhalgh AD. The Immune System's Role in the Consequences of Mild Traumatic Brain Injury (Concussion). Front Immunol. 2021 Feb 15; 12:620698
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