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

该项目的目的：该项目将定义临床程序，以便对患有肌张力障碍的儿童进行7T成像，并收集初步数据，以解决以下问题：与标准护理3T MRI相比，7T MRI是否改善了基底节核团的定位和对植入的DBS电极的连接性进行建模的能力。背景：肌张力障碍是一种痛苦的残疾状况，特征是无法控制的肌肉收缩。儿童肌张力障碍最常见的原因是CP，在英国，影响2-3：1000的活产儿。用来减少肌张力障碍的药物往往无效，而且严重的副作用限制了使用。肌张力障碍的症状不会对受影响的人自发缓解，因此缺乏有效的干预会导致长期的痛苦残疾。DBS可用于减轻脑性瘫痪患儿的肌张力障碍。电极被植入大脑的深层物质，连接到放置在皮肤下的神经刺激器(类似于起搏器)。DBS提供持续的电刺激，在刺激部位和更远的地方影响大脑。在DBS之后，CP儿童肌张力障碍的改善是不同的。以电极插入为靶点的基底节核非常小，边界在3T MRI上很难看到。这些核团有功能细分，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检查大脑的区域是如何连接的，通过“结构”和“功能”连接，可以让我们识别运动区。在植入DBS电极后，还可以测量大脑的哪些区域与DBS电极“连接”，帮助我们了解DBS是如何改善肌张力障碍的。Evelina伦敦儿童医院运营着英国领先的DBS儿童服务，并开创了针对肌张力障碍儿童的新型治疗方法。超高场MRI7T核磁共振扫描仪提供更高的神经解剖学清晰度，将更精确地定义靶核及其连接情况。然而，7T成像在技术上具有挑战性，需要详细的前期工作才能使儿童的临床成像成为可能，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建立了惠康信托伦敦超高场磁共振中心(Pi Hajner)，该中心有一个特定的儿科研究主题(Pi Edwards)。我们的小组被资助开发适当的婴儿和儿童成像序列(Pi Carmichael)。我们在儿童MR研究方面有既定的记录，包括由欧洲研究理事会资助的正在进行的1500万欧元发展人类连接组项目。影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一个独特的机会。我们计划做的是：我们将招募10名因接受DBS手术而患有脑瘫的儿童，并从3T和7T MRI扫描仪获得MRI图像。我们将使用这些图像来构建和比较基底神经节以及连接它们的白质通路的三维模型。我们将比较这些图像如何向我们展示从植入的电极到大脑不同区域的连接，以帮助我们了解DBS如何影响大脑。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通过核磁共振扫描测量的连接有多准确地再现了大脑的实际连接。这将如何帮助儿童：更好地了解基底神经节是如何连接的将帮助我们理解为什么患有CP的儿童会出现肌张力障碍。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，以确保每个儿童都能获得尽可能好的结果。

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.