Ultra-high resolution 7T MRI mapping of basal ganglia connectivity on an individual patient basis for Paediatric Deep Brain Stimulation (DBS)

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Aims of the Project:This project will define clinical procedures to allow 7T imaging in children suffering from dystonia and collect preliminary data to address the question: 'does 7T MRI improve the localisation of basal ganglia nuclei and the of modelling the connectivity profile of implanted DBS electrodes, compared to standard-of-care 3T MRI'.Background:Dystonia is a painful disabling condition, characterised by uncontrollable muscle contractions. The commonest cause of dystonia in childhood is CP, affecting 2-3:1000 live births in the UK. Medications used to reduce dystonia are often ineffective, and significant side effects limit use. Symptoms of dystonia do not spontaneously remit for affected individuals, and so a lack of effective intervention leads to long term painful disability. DBS may be used to reduce dystonia in children with CP. Electrodes are implanted into the deep substance of the brain, connected to a neurostimulator placed under the skin (similar to a pace-maker). DBS delivers a continuous electrical stimulus, which effects the brain at the site of stimulation and beyond. Following DBS, improvements in dystonia seen in children with CP is variable. The basal ganglia nuclei targeted for electrode insertion are very small, with boundaries that can be difficult to see on 3T MRI. These nuclei have functional subdivisions, the motor area being the target for electrode insertion. Advanced neuroimaging techniques can allow us to examine how regions of the brain are connected, through "structural" and "functional" connectivity, which can allow us to identify the motor area. It is also possible to measure which areas of the brain are "connected" to DBS electrodes after they are implanted, helping us to understand how DBS works to improve dystonia.The Evelina London Children's Hospital runs the leading DBS service for Children in the UK, and has pioneered novel treatments for children with dystonia.Ultra-high field MRI7T MRI scanners provide much higher neuroanatomical definition, and will define the target nuclei and their connectivity profiles with greater precision. However 7T imaging is technically challenging and detailed preliminary work is needed to make clinical imaging of children possible and to assess its value in clinical practice. We have recently established the Wellcome Trust London Ultra-high Field MRI Centre at the St Thomas' Campus of King's College London (PI Hajnal), with a specific paediatric research theme (PI Edwards). Our group is funded to develop appropriate sequences for imaging infants and children (PI Carmichael). We have an established track record of MR research in children, including the ongoing 15 million Euro Developing Human Connectome Project, funded by the European Research Council. This combination of imaging facilities and researchers with the DBS service offers a unique opportunity to make significant progress.What we plan to do:We will recruit 10 children with CP due to undergo DBS surgery and obtain MRI images from both 3T and 7T MRI scanners. We will use these images to build and compare 3-dimensional models of the basal ganglia, and the white matter pathways that connects them. We will compare how these images show us the connections from implanted electrodes to different regions of the brain, to help us understand how DBS effects the brain. Following surgery we will also perform a technique called DBS Evoked Potential (DBSEP). This technique will allow us to measure how accurately the connections we measure from MRI scans reproduce the actual wiring of the brain.How will this help children:A better understanding of how the basal ganglia are connected will help us to understand why children with CP experience dystonia. A better understanding of how DBS works in children with CP will help us better select children for surgery, and to better plan the placement of DBS electrodes to make sure each child experiences the best outcome possible.