Realising the benefits of structural and functional MRI at ultra-high-field

The quality of Magnetic Resonance Imaging (MRI) improves as the field strength of the scanner increases. Most hospitals in the UK have 1.5T scanners, but at the Sir Peter Mansfield Magnetic Resonance Centre in Nottingham we are exploring the potential of a 7T MRI scanner, currently the only one of its kind in the UK. We have already shown that this system gives significantly better quality pictures of the brain, and this will be further improved by the new hardware and software we plan to develop. This should enable us to find the ?missing lesions? in multiple sclerosis and to study changes in the brain associated with a range of neurodegenerative diseases, including Parkinson?s disease. We will validate some of the methodology using post mortem specimens, and then transfer it to patients. This will quickly lead to improved diagnosis and eventually to improved treatment. Ultra-high-field (7T) is particularly benefitial when MRI is used to study brain function. We will develop techniques for quantifying brain activity, and will combine images from MRI with data from other imaging methods, to identify networks of brain activity. Once developed, these techniques will provide a safe, non-invasive way for neuroscientists to explore and understand brain function, which remains one of our greatest scientific challenges. In Nottingham we will use these techniques to understand what the brain is doing when it is apparently resting, and how sequences of movement are learnt. We will also use them us to understand better the origins of some mental health problems. For example we will explore what happens when the brain fails to recruit a brain network appropriately, which is thought be the cause of inappropriate behavioural responses in Tourette?s syndrome, as well as some of the clinical symptoms of schizophrenia. Although our research involves leading edge facilities that are unlikely to become widely available in the near future, we anticipate that we will be able to find ways to transfer the most clinically promising methods to the lower field MRI systems that are to be found in almost every hospital in the UK.

Ultra-high-field has delivered the expected improvement in sensitivity which we have exploited to increase the spatial resolution of structural and functional MRI (fMRI). In structural imaging, we are now fast approaching a resolution limit set by subject movement, which we aim to overcome by developing a motion tracking system. The limited performance of whole-body gradient systems poses a further restriction on achievable resolution. We will therefore exploit the potential of a novel insert gradient coil set to produce higher gradients at the threshold for peripheral nerve stimulation. Static (B0) and radiofrequency (B1) magnetic field inhomogeneities remain significant challenges at 7T; we will develop new B0-shimming strategies and explore ?multiple transmit? and ?travelling wave approaches for achieving B1-uniformity. Susceptibility effects contribute to enhanced contrast at 7T, but can be difficult to interpret. We will therefore develop quantitative methods for susceptibility mapping and relate the resulting maps to tissue iron content. We will also develop chemical exchange saturation transfer (CEST) techniques as a measure of myelination. We will validate these techniques using post mortem specimens and use them in vivo, together with more conventional MR contrast parameters, to detect boundaries between functional domains, to distinguish between white matter ischaemic and MS lesions, improve detection of cortical MS lesions and to measure iron content in the subcortical nuclei of patients with Parkinson?s disease. The improved spatial resolution we aim to achieve for fMRI will allow us to investigate the fine-grained functional organisation of the auditory cortex and to probe columnar organisation in other sensory areas. We will also develop improved methods of measuring haemodynamic parameters and use these to refine methods of calibrating the BOLD response at 7T. In linearity studies we will compare cerebral metabolic rate of oxygen (CMRO2) derived from the BOLD signal and other haemodynamic parameters with 13C MRS measurements of energy metabolism. We will also compare them to measures of electrical activity (MEG and EEG). We have already established a close correlation between electromagnetic and MR measures; we now wish to examine this relationship across different frequency bands and, using 1H and 13C MRS, relate it to the levels and turnover of excitatory and inhibitory neurotransmitters. We will develop muti-modal (MEG/EEG and EEG/fMRI) methods for this purpose. These methods will also be used to distinguish between network models of motor learning, and to compare the ?salience? network between control subjects and schizophrenics in whom it may be deficient.