Designing and Imaging Tumoroids to Test the Sensitivity of MRI Susceptibility Mapping to Hypoxia in Cancer
Hypoxia is found in many tumours and is emerging as a useful indicator of tumour grade and a biomarker for poor response to radiotherapy. The clinical challenge is to determine the oxygenation levels inside tumours non-invasively. MRI susceptibility mapping uses MRI phase images to calculate the local tissue magnetic susceptibility. The susceptibility of blood changes dramatically depending on its oxygenation making MRI susceptibility mapping an ideal candidate to reveal oxygenation in vivo. Work is underway to optimise MRI susceptibility mapping for tumours in vivo. However, there is no non-invasive way to validate this technique and test how sensitive it is to the very low oxygen levels commonly found in tumours.
The aim of this project is to design tumoroids – realistic 3D cellular models of tumours – with oxygen gradients mimicking those in real tumours and to image them to test the sensitivity of MRI susceptibility mapping to these low oxygenation levels. Oxygenation levels calculated from MRI susceptibility maps of tumoroids will be compared with oxygen levels measured independently using gold-standard fibre-optic oxygen probes in the same tumoroids.
This challenging project will involve design and fabrication of 3D tumoroids in vitro with realistic oxygenation gradients as well as optimising high-resolution MRI acquisition and susceptibility mapping techniques for tumoroids and performing calibrated fibre-optic oxygenation measurements.Dr Cheema’s lab is world-leading in tumoroid construction and evaluation and Dr Shmueli pioneered the technique of MRI magnetic susceptibility mapping and leads a group with expertise in this rapidly evolving field.
This vital work to demonstrate how sensitive MRI susceptibility maps are to tumour hypoxia will help move this cutting-edge technique further along the translational pipeline into the clinic. It may also provide an ideal model system for testing of therapeutic agents such as those designed to increase tumour oxygenation to improve the effectiveness of radiotherapy and chemotherapy.This project will focus on designing and constructing realistic 3D engineered tumour models containing cell cultures – tumoroids – and imaging them to help translate a non-invasive technique (MRI susceptibility mapping) for oxygenation imaging into the clinic. This MRI susceptibility mapping technique will help cancer imaging in future by providing a non-invasive, validated biomarker of the hypoxic status of cancers enabling targeting and/or sensitisation of hypoxic sites to maximise radiotherapeutic effect. The tumoroid + MRI model system may also be useful to test therapeutic agents designed to increase tumour oxygenation.
MRI of tumoroids is non-trivial, requiring careful set-up to ensure cell viability and temperature stability. It will also be challenging to develop artefact free susceptibility mapping MRI pulse sequences that provide high-resolution maps of tumoroid oxygenation. In addition to these image acquisition challenges, we will optimise the image processing methods required for image reconstruction: calculation of accurate susceptibility maps from MRI phase images using and developing the wide variety of exciting new susceptibility mapping techniques to solve this inverse problem.
Dr Steve Bandula (UCLH and UCL Centre for Medical Imaging) will also be involved in supervising this work, building on his preliminary published work on MRI of tumoroids.