MRI Hypoxia Study for Glioblastoma Multiforme (GBM) Radiation Therapy

Magnetic Resonance Imaging of Hypoxia for Radiation Treatment Guidance in Glioblastoma Multiforme (MANGO)

This study is designed to evaluate the role of Oxygen Enhanced (OE) Magnetic resonance imaging (MRI) and Blood Oxygenation Level Dependent (BOLD) MRI in detecting regions of hypoxic tumour and to evaluate their use as imaging methods to selectively deliver targeted radiotherapy to regions of aggressive disease.

The ability to image tumour hypoxia at diagnosis and prior to radiotherapy is extremely important to appropriately adapt radiotherapy plans such that to selectively deliver higher doses of radiation to those more aggressive tumour subregions, thereby improving the chances to achieve better local tumour control. Preoperative imaging of tumour hypoxia also offers the opportunity for 'supra-marginal resections' in surgical planning beyond current neurosurgical standard of care. Additionally, accurately identifying regions of tumour hypoxia harbouring tumour progression at follow up is fundamental in patient follow-up, allowing multidisciplinary teams to more confidently intervene at an earlier stage of tumour recurrence and personalise therapy tailored to the tumour's response to treatment. Routine imaging of tumour hypoxia is currently challenging, as it requires [18F]-Fluoromisonidazole (18F-FMISO PET) imaging, which is not available in the majority of clinical centres. Today, the availability of accelerated quantitative MRI sequences on clinical MRI systems could enable quantification of tumour hypoxia without putting an unfeasible burden on patients' scan sessions. The next frontier in radiotherapy treatment will use these techniques to identify hypoxic tumour tissues and personalise treatments to the patient's unique tumour biology, maximising the probability of tumour control.

This clinical study will acquire additional images of brain cancer patients. The images will not change the patient's treatment. This study is designed to evaluate the role of oxygen enhanced (OE) MRI and BOLD MRI in detecting regions of hypoxic tumour and to evaluate their use as imaging methods to selectively deliver targeted radiotherapy to regions of aggressive disease.

Inclusion Criteria:

• Suspected high-grade glioma (HGG) / glioblastoma multiforme (WHO grade IV) at initial radiological examination
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
• Available for scanning on two separate days

Exclusion Criteria:

• Women lactating, pregnant or of childbearing potential who are not willing to avoid pregnancy during the study
• Patients with a history of severe renal disease(s) (eGFR <20) that cannot tolerate gadolinium chelate contrast agents.
• Geographically remote patients unable to agree to imaging schedule
• Patients who have received anti - vascular endothelial growth factor (anti-VEGF) monoclonal antibody therapy the 3 months prior to recruitment
• Patients with a history of psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.
• Patients with significant cardiac or pulmonary disease including cardiac arrythmias or Chronic Obstructive Pulmonary Disease (COPD) that are unable to tolerate high flow O2 for oxygen contrast.
• Patients taking carbonic anhydrase inhibitors (Acetazolamide)
• History of glaucoma
• Any implant, foreign body, 3 Tesla (3T) MRI incompatible device, or other contraindication to MRI imaging.