Research (MRI physics)

The locus coeruleus (LC) is a small structure (or nucleus) within the brain that undergoes degeneration early on in the progression of Alzheimer’s disease (AD). Structural imaging of the LC and functional connectivity of the LC along with correlations to other clinical measures could serve as a biomarker for AD. (See image below)

Inflammation is a key component of the dementia pathway, and we are interested in how it changes the brain, using advanced imaging techniques. Inflammation may affect the brain via the blood brain barrier (BBB), with inflammation leading to a ‘leakier’ blood brain barrier. Dynamic contrast-enhanced MRI (DCE-MRI) is a non-invasive method of detecting subtle changes in BBB leakiness and we are measuring this parameter in AD patients compared to healthy controls, as well as in relation to other markers of inflammation and over a long time period, relating it to cognitive changes in this time period. This should enable us to both look at the mechanisms involved in AD, to help direct treatments, as well as developing an imaging tool to help with prognosis of AD.

Currently dementia diagnosis and severity are partly evaluated using perfusion measured using radionuclide techniques. We are beginning a study to see whether MRI measures of perfusion can be used for this purpose. The method we are using is called arterial spin labelling, and does not require the use of injected contrast agents.

We are working with a commercial company, Oxford Brain Diagnostics, to help them test their novel brain imaging technique, cortical disarray measurement (CDM), which looks at the tissue structure of the brain as a marker of AD. 

As well as inflammatory components of dementia, vascular issues are well known to be contributory to the disease process. We are interested in examining how the brain vasculature changes, both functionally and structurally, in relation to other factors, including inflammation, using a variety of MRI techniques.

Systemic inflammation induces immune responses that can cause damage to the the central nervous system. To investigate the impact of systemic inflammation on multiple sclerosis (MS) progression, we have been collaborating with researchers at the University of Southampton by measuring blood-brain barrier permeability using dynamic contrast-enhanced MRI.

Brain aneurysms are often identified accidentally when patients are being scanned for another purpose. It would be useful to be able to distinguish between those aneurysms which are stable and those which might rupture and would benefit from early intervention. We are exploring whether the leakiness of the aneurysms, measured using dynamic contrast-enhanced MRI, is useful for this application.

We are active in supporting various research projects in the departments of psychology and psychiatry at the University. These projects usually involve examining different brain functions and processes, using a technique called functional MRI.

Hydrocephalus patients have excess cerebrospinal fluids (CSF) in the brain and cannot drain promptly, causing tissue damage due to increased pressure. We are investigating whether resting-state functional MRI can be used to assess the patency of new CSF drainage pathway created by surgery such as endoscopic third ventriculostomy, and how the CSF flow signals couple with heart rate and breathing. We are also interested in how signals from various MRI techniques can be used to characterise changes in neurofluid (CSF, interstitial fluid and blood) properties, to elucidate mechanisms and interactions in a range of diseases, including dementia.

We have been involved in a range of projects in neonatal hypoxic ischaemic encephalopathy (a brain injury at birth). In a similar way to our dementia work, we are using a range of MRI techniques to look at disease mechanisms involved in HIE as well trying to improve prognosis for these children, using MRI data.

One of our first HIE projects was to look at the appearance of the veins in the brain in babies with HIE, using a technique called ‘susceptibility weighted imaging’ (SWI), which picks up the deoxygenated blood in the veins and highlights these structures well. We have collaborated with computer scientists at the University to perform detailed analysis of these images to see whether we can produce metrics that can be used to predict outcomes in these babies, reflective of brain oxygenation changes in the neonatal period.

Babies who have suffered hypoxic ischaemic encephalopathy (HIE) around the time of birth often appear to experience subsequent hyper perfusion (investigated here initially using SWI - see above), which is thought to be responsible for some of the subsequent tissue damage. We are testing whether more accurate MRI measurements of perfusion in sensitive brain structures correspond with neurodevelopmental outcome (measured at 1 and 2 years), and could therefore identify which babies would benefit from early intervention and which will do well without additional treatment. We are also using MR spectroscopy to test whether there are biochemical differences in brain tissues of different HIE babies, regarding the relative accumulations of lactate, which might correlate with subsequent clinical outcome.

We are applying machine learning techniques to the standard clinical MRI scans acquired in HIE patients within the first few days after birth, to predict outcomes at 2 years of age and are investigating factors that contribute to this prediction.

Another area of HIE research we have been peripherally involved in over the years is using diffusion MRI and functional MRI to highlight structural and functional brain networks in babies with HIE and how these change with disease severity and age (from neonates to school-age children). We have been working with mathematicians at the University to further interrogate these networks, using ‘topological’ approaches, to characterise these changes more fully.

Prostate cancer is the second most common cancer in males. Some cases develop only slowly, whilst others are more aggressive. Detection and progression increasingly utilise MRI in addition to tissue sampling and other clinical measures. We are part of the CLIMATE multi-centre study (Comparison of diagnostic accuracy of Luminal Index and Multi-parametric MRI for Accelerated deTEction of significant prostate cancer) which is testing a new MR imaging technique which reflects the amount of luminal water. Luminal water is high in normal prostate but very low in cancers, and so this relatively simple method is proposed to improve on sensitivity and specificity of detection and characterisation of the disease.

Traditionally, MRI has poor contrast in the lungs due to the low concentration of water molecules and rapid decay of the MR signal. Novel techniques have been developed to enable structural and functional imaging of the lungs. These could greatly benefit paediatric patients that currently require annual scans using imaging modalities with ionising radiation. We are interested in implementing these new lung imaging techniques to provide additional information about lung oxygenation, perfusion, ventilation and structure, to help monitor the development of various lung conditions across the life course

We have been involved in several projects over the years, looking at various aspects of liver disease, particularly non-alcoholic fatty liver disease (NAFLD). This has included quantifying fat in subcutaneous and visceral regions of the abdomen using MRI images, calculating fat fraction in the liver and helping establish quantification techniques to look at liver inflammation (in collaboration with Perspectum). We are also now involved in a project characterising liver tumours using advanced MRI techniques such as dynamic contrast enhanced MRI.

This is another area of work we have been involved in over the last two decades, mainly using MRI images to quantify soft tissue structures in the body. This has often been in conjunction with bioengineers at the University to elucidate biomechanics and tissue properties in different diseases or clinical scenarios, such as in amputees and in relation to finger joint prosthetics.