Advanced functional MRI for the characterisation of paediatric glioma and its response to therapy

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Advanced functional MRI for the characterisation of paediatric glioma and its response to therapy

Project Description:
We are seeking a motivated PhD student with a background in Physics, Engineering or Biological Sciences to pursue an exciting project to develop and assess functional magnetic resonance imaging (MRI) methods for the interrogation of tumour growth and response to therapy in vivo in mouse models of paediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG).
DIPG and pGBM are leading causes of tumour-related morbidity and mortality in children and young adults, with median survival of 12-15 months. When compared to histologically similar tumours in older adults, paediatric disease displays distinct underlying biology, which differs by anatomical location. However, current primary treatment options remain based on adult protocols, incorporating radiotherapy and, where possible, surgery and chemotherapy. A major contributing factor to the lack of effective treatments has been the deficiency, until recently, of appropriate tumour models that emulate DIPG and pGBM, and accompanying biomarkers with which to accurately assess their progression and response to new therapeutic approaches, which this project will address.

The aims of the project are to:
Implement advanced multi-parametric MRI protocols to spatially and temporally interrogate the growth patterns of intracranial models of pGBM and DIPG, and correlate the imaging data with histopathology.
MRI is routinely used for the diagnosis and monitoring of paediatric brain tumours, and this project will develop, optimise and apply structural, metabolic and vascular MRI strategies to assess the evolving phenotype of orthotopic pGBM and DIPG models, and to assess differential treatment response to both standard-of-care treatment regimens and rational therapeutics targeted towards the pathways dysregulated in pGBM/DIPG.

To optimise targeted irradiation protocols for brain tumour treatment and assess response to radiotherapy using multi-parametric MRI.
Radiotherapy plays a major role in the frontline treatment strategies for pGBM and DIPG, therefore radiotherapy will be included in therapeutic approaches assessed in vivo, and will be performed using a small animal radiation research platform (SARRP), which replicates modern clinical radiotherapy for conformal treatment of rodent tumour models, minimising the exposure of normal tissues to irradiation.

Design MRI-embedded combination treatment protocols encompassing irradiation, novel targeted therapeutics and, if appropriate, standard chemotherapeutics.
Rational novel therapeutic targets for the selected in vivo models will be guided by genomic and methylation profiling and in vitro drug screening against a panel of approved chemotherapeutics and small molecules.

The project will be based within the Centre for Cancer Imaging in Sutton, which provides an integrated environment for multi-modality preclinical imaging, co-locating the different imaging and therapy equipment. The studentship will provide opportunities to interact within a multi-disciplinary environment of staff within imaging, radiotherapy, drug development and molecular pathology teams.
Keywords /Subject Areas:
Magnetic resonance imaging
Brain tumours
Childhood cancer
Radiotherapy
Cancer therapeutics