Next Generation Electrophysiological Imaging - Development and Application in Epilepsy

Human brain health has been revolutionised by techniques like MRI, which provide a non-invasive window on brain structure. However, in many diseases, structure appears normal, and it is changes in the function of brain cells that underly symptoms. It follows that next generation healthcare critically requires the development of techniques to measure brain function. A good example is epilepsy, where abnormal electrical activity in neural networks underlies symptoms. Epilepsy affects ~900,000 people in the UK and in ~30% of cases, symptoms are not controlled by medication. Patients become candidates for surgery, where the tissue generating seizures is removed. Extensive assessment is required to identify the regions to be removed, however this is a significant challenge. EEG (the standard technique to diagnose epilepsy) has poor spatial precision and cannot pinpoint the target regions. MRI doesn't always detect abnormalities and when it does, multiple abnormalities are often found, and we don't know which is responsible for seizures. The "gold standard" measurement involves placing electrodes in the brain. This gives a measurement of activity with the highest possible sensitivity and spatial precision. However, it requires major surgery. We will develop a new technology, which will be completely non-invasive, yet will rival the performance of invasive electrodes. Our system will use "quantum" sensors, which exploit the quantum properties of atoms to detect magnetic fields generated by brain activity - a process called magnetoencephalography (MEG). MEG is already a proven tool in research and has significant clinical applications - especially epilepsy. However, conventional scanners use low temperature sensors. Consequently, sensors are kept a long way from the head - limiting sensitivity and spatial precision. Our system will use sensors called OPMs, which can detect magnetic fields without low temperature. OPMs can be sited much closer to the scalp, providing higher sensitivity and spatial accuracy. Furthermore, because OPMs are very small, we can pack large numbers together in a 'high density' (HD) array, further improving sensitivity and spatial precision. Theory suggests that our new system, which we call "HD-OPM-MEG" will rival the performance of implanted electrodes. There are significant technical challenges that must be overcome to make HD-OPM-MEG work. We must understand the spatial patterns of magnetic field generated by the brain, and how those patterns differ in children and adults - this will help us design the best possible sensor arrays. We must develop novel devices to ensure that the magnetic fields we measure are accurate. We also need new tools to ensure that magnetic interference cannot impact our data. Having collected data, we need techniques to turn the measured fields into 3D images of activity - this includes novel methods to determine where on the scalp our OPMs are located. We will solve these fundamental problems; we will then undertake studies in healthy children and adults, to show that our new HD-OPM-MEG system can map electrical brain function with performance that has never before been achieved using a non-invasive technology. Finally, we will apply our system in patients with epilepsy, showing that we can map the regions responsible for seizures with a precision comparable only to that of invasive electrodes. HD-OPM-MEG will be a non-invasive imaging technique with unprecedented performance. Although our demonstration will be in epilepsy, this technology will revolutionise the capability of imaging across a wide range of neurological and psychiatric conditions.