Radiation and brain structure: how do these relate to cognitive and behavioural deficits in paediatric brain tumour survivors?

由于各种治疗策略的可用性，如手术和质子治疗，患有脑肿瘤的儿童的总体存活率急剧增加。然而，这些生存的改善伴随着严重的脑损伤。例如，在注意力、记忆力、在任务之间切换的能力、处理速度和读写能力方面的缺陷在幸存者中很常见。为了更好地理解这些损伤是如何产生的，成像技术已经被用来研究辐射对大脑结构的损害。磁共振成像（MRI）使我们能够拍摄大脑的照片。使用一种叫做扩散核磁共振成像的特殊技术，可以测量大脑结构的损伤程度，并绘制出空间图。目的和目标-具体目标是：本博士的目的是探索辐射剂量之间的关系，以及辐射剂量与大脑空间微结构损伤之间的关系，以及辐射剂量与治疗后缺陷之间的关系。研究样本将包括在UCLH接受质子治疗的颅咽管瘤、室管膜瘤或低级别胶质瘤的儿科患者。质子治疗数据将作为UCLH常规临床服务的一部分收集。定量MRI数据将作为GOSH常规临床服务的一部分收集。这分为以下几个目标：将MRI数据导入UCLH的放疗计划系统（Eclipse），并将其共同注册到治疗计划CT。根据剂量分布立方的逐点剂量对多壳扩散MRI得出的各种微结构参数进行评估。建立模型，对剂量、微观结构和认知之间的关系进行空间统计推断。研究方法的新颖性这项工作将利用最先进的成像方法在微观结构水平上绘制大脑损伤图。然后将采用新的图像配准技术将质子治疗剂量分布映射到这些损伤图。然后将开发新的和新颖的方法来模拟关于剂量、微观结构和认知之间关系的空间统计推断。与EPSRC的战略和研究领域保持一致本项目与以下EPSRC医疗技术重大挑战保持一致：物理干预的前沿；优化治疗。它还将建立以下交叉研究能力：新颖的计算和数学科学；新成像技术UCLH放射学系的任何公司或合作者。质子物理组组长Andy Poynter先生和UCLH质子治疗临床组长颜庆昌博士。大奥蒙德街医院放射科。放射学顾问Felice D'Arco博士

Brief description of the context of the research including potential impact The overall survival rate of children with brain tumours has increased dramatically due to the availability of various treatment strategies such as surgery and proton therapy. However, these improvements in survival are accompanied by serious brain impairments. For example, deficits in attention, memory, ability to switch between tasks, speed of processing and literacy are commonly seen in survivors. To better understand how these impairments arise, imaging techniques have been used to investigate damage to structure of the brain as a result of irradiation. Magnetic resonance imaging (MRI) allows us to take pictures of the brain. Using a special technique called diffusion MRI it is possible to measure the degree of damage to the brain structure and to map this spatially. Aims and Objectives -The specific objectives are to: The aim of this PhD is to explore the relationship between radiation dose and how this relates to microstructural damage in the brain spatially and in turn how this is associated with post-treatment deficits. The study sample will consist of paediatric patients with craniopharyngioma, ependymoma or low grade glioma undergoing proton therapy at UCLH. Proton therapy data will be collected as part of the routine clinical service at UCLH. Quantitative MRI data will be collected as part of the routine clinical service at GOSH. This is split into the following objectives: Import MRI data into the radiotherapy planning system (Eclipse) at UCLH and co-registering this to the treatment planning CT. Assessment of various microstructural parameters derived from multi-shell diffusion MRI against the point by point dose from the dose distribution cube. Development of models to make spatial statistical inferences regarding the relationships between dose, microstructure and cognition. Novelty of Research Methodology This work will utilise state-of-the-art imaging approaches to map damage to the brain at the microstructure level. Novel image registration techniques will then be employed to map proton therapy dose distributions to these damage maps. New and novel approaches will then be developed for modelling the spatial statistical inferences regarding the relationships between dose, microstructure and cognition. Alignment to EPSRC's strategies and research areas This project is aligned with the following EPSRC Healthcare Technologies Grand Challenges: Frontiers of Physical Intervention; and Optimising Treatment. It also will build the following Cross-cutting research capabilities: Novel computational and mathematical sciences; Novel Imaging Technologies Any companies or collaborators involved UCLH Radiotherapy Department. Mr Andy Poynter, Proton Physics Group Lead and Dr Yen Ching Chang, the clinical lead for proton therapy at UCLH. Great Ormond Street Hospital, Department of Radiology. Radiology Consultant Dr Felice D'Arco