Title: Developing MRI Magnetic Susceptibility-Based Cancer Oxygenation Mapping (SBCOM) and Investigating its Clinical Potential to Measure Hypoxia in Prostate Cancer (PCa) and Head and Neck Squamous Cell Carcinoma (HNSCC)
Funder: Cancer Research UK

Abstract: Background Hypoxia predicts survival and poor therapeutic response in many tumours including prostate cancers (PCa) and head and neck squamous cell carcinoma (HNSCC). Therapeutic options are arising for correcting hypoxia to maximise radiotherapeutic effect but there is an unmet clinical need to measure tumour oxygenation levels non-invasively to identify and target treatment-resistant tissues. To meet this need, we aim to develop a new technology based on MRI quantitative magnetic susceptibility mapping (QSM), a recent technique we have pioneered. Although blood’s susceptibility is directly proportional to oxygenation and QSM is beginning to reveal cerebral venous oxygenation, there are many physics and engineering challenges to address to create a QSM-based technology to measure oxygenation within cancerous tissue. Aims We aim to develop a new technology: Susceptibility-Based Cancer Oxygenation Mapping (SBCOM) in HNSCC and PCa and to investigate its clinical potential to non-invasively determine these cancers’ hypoxic status. Methods Based on our expertise in MRI Physics and QSM, and our extensive clinical experience in translational cancer MRI, we will develop new QSM MRI acquisition techniques for the head-and-neck and prostate regions. We will incorporate flow compensation, suppression of fat-water phase cancellation artifacts and acceleration to reduce motion artifacts. Numerical phantoms will be used to optimise QSM reconstruction techniques for SBCOM. To investigate which combination of susceptibility values most closely reflects hypoxia, we will develop new QSM image analysis techniques to find reference tissue regions and segment MRI-visible veins which are bright in susceptibility maps. To investigate whether SBCOM can reveal clinically relevant hypoxia, we will test it in PCa patients against pimonidazole staining, the gold-standard invasive histological method of measuring oxygenation. We expect to see a strong correlation between SBCOM susceptibility-based measures and histologic tumour de-oxygenation. How the results of this research will be used This research will underpin the use of SBCOM for non-invasive identification of hypoxic tumours and nodes in patients to inform and improve treatment effectiveness. The translational pathway for SBCOM will follow CRUK’s imaging biomarker roadmap including multi-centre trials and exploit UCL/H’s proven translational pipeline for incorporating locally-developed innovative MRI techniques into clinical protocols. To facilitate this translation, SBCOM acquisition, reconstruction and analysis code will be streamlined into user-friendly, clinically-compatible software. SBCOM has the potential to assist treatment planning and monitoring, to significantly improve prognosis and to allow more personalised treatment according to hypoxic status for improved survival in PCa, HNSCC and many common solid cancers.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS