Methodology for the robust in-vivo multi-centre Evaluation of glucose meTabolism with Hyperpolarised 13C-MRI: foundations towards avoiding unnecessary Overtreatment of inDolent prostate cancer (METHOD)

Background: Early detection of prostate cancer should be a combination of two unique challenges: the first, is localising the disease and this already had a significant amount of attention (mpMRI works well); the second is disease characterisation and remains a clinical challenge. There is a need for technology wherein the longitudinal outcome of organ confined early cancer can be better determined; avoiding unnecessary treatment and limiting the extent of treatment required. HP-MRI (HP-MR) is a novel, imaging technology, used for the in-vivo measurement of glucose metabolism. Early studies of the biology of prostate cancer and HP-MRI suggests that glucose metabolism is significant in aggressive cancers (1). It has been measured in the prostate with HP-MRI at multiple expert centres with all showing that it is higher in areas of cancer than surrounding prostate tissue (2,3). At UCL, we have demonstrated (unpublished) early results that men who progress on active surveillance within 2 years are more likely to have higher cancer metabolism on entry into the program i.e. metabolism may be a good prognostic indicator. The next step is to conduct a powered trial, which will require multi-centre data pooling, but different hardware/software across different sites results in measurement differences making pooling difficult. Aims: Within this fellowship, I will establish the foundations that will enable multi-centre HP-MRI studies, by developing the methodology that can allow for calibration clinical HP-MRI measures or metabolism across multiple centres. A calibration approach is unique in quantitative MRI, as most approaches to date have relied upon controlling all the technical factors that go into acquiring and creating MRI images to minimise variations in measurements, but these are difficult to implement in clinical practice and remain in the research domain. Methods: This planned body of work will involve: the technical development of phantoms, to identify an optimal metric for metabolic assessment and to calibrate measurements across multiple centres; a standardised data acquisition, processing, and analysis protocol. The fellowship will culminate in a proof of principle study whereby the phantom derived calibration will be applied to human HP-MRI scans performed with different hardware/software on the same patient volunteers. How results will be used: The work will also underpin further approaches for calibration across a range of quantitative MRI methods and also the specific application of the developed methodology across centres in a large prospective trial of the HP-MRI technology for prognostication in men with prostate cancer.