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

项目目的：该项目将定义临床程序，允许对患有肌张力障碍的儿童进行7T成像，并收集初步数据来解决以下问题：“与标准的3T MRI相比，7T MRI是否改善了基底神经节核的定位和植入DBS电极的连接谱建模？”背景：肌张力障碍是一种痛苦的残疾状况，其特征是无法控制的肌肉收缩。儿童期肌张力障碍最常见的原因是CP，在英国影响2-3:10 000活产婴儿。用于减轻肌张力障碍的药物通常无效，并且明显的副作用限制了使用。肌张力障碍的症状不会自发缓解，因此缺乏有效的干预会导致长期痛苦的残疾。DBS可用于减轻CP患儿的肌张力障碍。电极被植入大脑深层，与皮下的神经刺激器相连（类似于起搏器）。DBS提供持续的电刺激，对刺激部位及其他部位的大脑产生影响。DBS后，CP患儿肌张力障碍的改善情况不一。电极插入的基底神经节核非常小，在3T MRI上很难看到边界。这些核具有功能细分，运动区是电极插入的目标。先进的神经成像技术可以让我们通过“结构”和“功能”连接来检查大脑区域是如何连接的，这可以让我们识别运动区域。在植入DBS电极后，还可以测量大脑的哪些区域“连接”到DBS电极，这有助于我们了解DBS是如何改善肌张力障碍的。Evelina伦敦儿童医院为英国儿童提供领先的DBS服务，并开创了针对肌张力障碍儿童的新疗法。超高场MRI扫描仪提供了更高的神经解剖学清晰度，并将以更高的精度定义目标核及其连通性。然而，7T成像在技术上具有挑战性，需要详细的前期工作，使儿童临床成像成为可能，并评估其在临床实践中的价值。我们最近在伦敦国王学院圣托马斯校区（PI Hajnal）建立了威康信托伦敦超高场核磁共振中心，具有特定的儿科研究主题（PI Edwards）。我们的小组得到资助，开发适合婴幼儿成像的序列（PI Carmichael）。我们在儿童核磁共振研究方面有着良好的记录，包括正在进行的由欧洲研究委员会资助的1500万欧元的发展人类连接体项目。成像设备和研究人员与DBS服务的结合为取得重大进展提供了独特的机会。我们计划做的是：我们将招募10名即将接受DBS手术的CP患儿，通过3T和7T MRI扫描仪获取MRI图像。我们将使用这些图像来建立和比较基底神经节的三维模型，以及连接它们的白质通路。我们将比较这些图像如何显示从植入电极到大脑不同区域的连接，以帮助我们了解DBS是如何影响大脑的。手术后，我们还将进行一项名为DBS诱发电位（DBSEP）的技术。这项技术将使我们能够测量我们从核磁共振扫描中测量到的连接对大脑实际线路的再现有多准确。这对儿童有何帮助：更好地了解基底神经节是如何连接的，将有助于我们理解为什么患有CP的儿童会经历肌张力障碍。更好地了解DBS在CP儿童中的作用将有助于我们更好地选择儿童进行手术，并更好地计划DBS电极的放置，以确保每个孩子都能获得最好的结果。

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.