Development of MRI markers of brain inflammation

Neuroinflammation occurs as part of the normal physiological immune response in the nervous tissue, in which cells

respond to infection, toxins and injury in order to protect the brain. Throughout life, the brain is exposed to multiple insults such as viruses, pollution and impacts to the head, particularly in sport, which can lead to chronic neuroinflammation

involving blood-brain barrier breakdown and may affect healthy aging. There are very few in vivo measurements with which

we can study this process. The aim of this project is to develop quantitative, validated, magnetic resonance imaging (MRI) measurements of neuroinflammation during aging for use in rodents and people. The measurements developed will be ultimately deployed in rugby players who, being exposed to multiple impacts to the head, we hypothesise will have high

levels if neuroinflammation and accelerated brain aging, which will be useful to test our imaging measurements.

to protect the brain. Throughout life, the brain is exposed to multiple insults such as viruses, pollution, impacts to the head during sport, which can lead to chronic neuroinflammation involving blood-brain barrier breakdown. 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. 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 with reduced scan time. 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, measurements of water exchange across

the blood-brain barrier and the use of ultra-small iron oxide particles that get taken up by circulating immune cells that then cross into the brain. Diffusion-weighted MRI is another approach in which changes in cell morphology during

neuroinflammation can be detected by sensitising the MRI signal to microstructural barriers to diffusion. We will use rodent models of neuroinflammation to optimise and validate these measurements. Finally, a combination of these new and optimised measurements will be applied in rugby players who, being exposed to

multiple impacts to the head, we hypothesise will have high levels of neuroinflammation which will be useful to test our imaging measurements. We will compare measurements between rugby players and a young healthy active group (rowers) and also with an older healthy group to understand the relative contribution of head impact and ageing to

neuroinflammation.