Development of MRI-compatible Graphene-based Probes for Rodent and Human Electrophysiology

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A common treatment for patients with severe, drug-resistant epilepsy is to surgically remove the abnormal brain tissue responsible for recurring seizures, often referred to as the epileptic focus. The identification of the focus can be achieved by recording brain waves within the brain using special electrodes implanted surgically. However, in many cases it is still not easy to discover which part of the brain to remove partly because the electrodes currently used were developed prior to the magnetic resonance imaging (MRI) era, and contain a large amount of metal which results in large artefacts in MRI images acquired after their implantation to verify their location. These artefacts obscure the electrodes' location, making it difficult to visualise the brain tissue around them, a limitation with important clinical implications. Metal-based electrodes within the MR environment also pose several safety concerns that arise from interactions between the probe and the fields used in MRI. We recently showed that a new type of electrode, called graphene-based (Graphene Solution-Gated Field-Effect Transistors, or gSGFET) probes, have several advantages over existing electrodes, including a much reduced amount of metal that can interfere with MRI and the ability to record brain waves in a radically new way due to their electronic design. For example, the new gSGFET are able to record brain oscillations that are much slower than those that can be recorded using the current metal electrodes. There is mounting evidence that it is important to be able to measure such slow electrical brain activity. Up to now, the new electrodes have been made for recording in small animals and we now want to move this technology towards the clinic, promising to shed new light on the brain regions responsible for epileptic seizures. The proposed developments will ensure the new probe technology's maximal scientific impact and clinical utility.We will develop, test and implement a modified gSGFET probe design by the addition of features that are specifically conceived to make them visible and localisable with great precision in MRI images. We will perform experiments to improve and validate the new design, with the aim of obtaining sub-millimetric accuracy. We will then demonstrate the probes' new capabilities in terms of localization, visualization and brain signal quality by performing recordings in preclinical models. Finally, we will build upscaled prototypes of clinical probes and subject these to technical tests.Success of this work will allow future first-in-human studies, where both the improved brain wave recording characteristics and MR compatibility of the new gSGFET probes could have a significant impact on epilepsy management including pre-surgical planning. Beyond specific epilepsy considerations, the strategy for improving the appearance of the probes on MRI images developed during this proposal will have applications for the investigation of other neurological conditions, and could be adapted to other nonmagnetic materials considered for more complex brain-machine interfaces to make them visible in MRI. For example, a similar approach to make MRI-compatible deep brain stimulation (DBS) electrodes used to treat movement disorders such as Parkinson's disease with graphene-based technology will allow improved probe targeting and visualisation, and more effective treatment as a result. In addition, the new electrode technology has important potential applications for the study of normal brain activity since data obtained from brain indwelling electrodes is also used to study the nature of brain signals such as functional MRI and scalp EEG, and their inter-relationship.