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

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

The critical mass of scientists and engineers that i4health will produce will ensure the UK's continued standing as a world-leader in medical imaging and healthcare technology research. In addition to continued academic excellence, they will further support a future culture of industry and entrepreneurship in healthcare technologies driven by highly trained engineers with deep understanding of the key factors involved in delivering effective translatable and marketable technology. They will achieve this through high quality engineering and imaging science, a broad view of other relevant technological areas, the ability to pinpoint clinical gaps and needs, consideration of clinical user requirements, and patient considerations. Our graduates will provide the drive, determination and enthusiasm to build future UK industry in this vital area via start-ups and spin-outs adding to the burgeoning community of healthcare-related SMEs in London and the rest of the UK. The training in entrepreneurship, coupled with the vibrant environment we are developing for this topic via unique linkage of Engineering and Medicine at UCL, is specifically designed to foster such outcomes. These same innovative leaders will bolster the UK's presence in medical multinationals - pharmaceutical companies, scanner manufacturers, etc. - and ensure the UK's competitiveness as a location for future R&D and medical engineering. They will also provide an invaluable source of expertise for the future NHS and other healthcare-delivery services enabling rapid translation and uptake of the latest imaging and healthcare technologies at the clinical front line. The ultimate impact will be on people and patients, both in the UK and internationally, who will benefit from the increased knowledge of health and disease, as well as better treatment and healthcare management provided by the future technologies our trainees will produce.

In addition to impact in healthcare research, development, and capability, the CDT will have major impact on the students we will attract and train. We will provide our talented cohorts of students with the skills required to lead academic research in this area, to lead industrial development and to make a significant impact as advocates of the science and engineering of their discipline. The i4health CDT's combination of the highest academic standards of research with excellent in-depth training in core skills will mean that our cohorts of students will be in great demand placing them in a powerful position to sculpt their own careers, have major impact within our discipline, while influencing the international mindset and direction. Strong evidence demonstrates this in our existing cohorts of students through high levels of conference podium talks in the most prestigious venues in our field, conference prizes, high impact publications in both engineering, clinical, and general science journals, as well as post-PhD fellowships and career progression. The content and training innovations we propose in i4health will ensure this continues and expands over the next decade.