Oxygen Enhanced-MRI for Hypoxia Imaging in Head and Neck Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Hypoxia is an important predictor of treatment efficacy in head and neck (H&N) cancer. Oxygen-enhanced (OE)-MRI is a non-invasive method for mapping and quantifying the extent of regional hypoxia, by identifying tumor regions that are perfused but refractory to oxygen change (termed perfused oxygen refractory, or pOxy-R). The aim of this work was to develop OE-MRI in H&N carcinoma and measure pOxy-R during (chemo)radiotherapy ((C)RT) and to then translate OE-MRI onto an MRI-Linac (MRL), with a longer term aim of using the technique for biologically adaptive radiotherapy. We hypothesized that pOxy-R proportion would reduce during the treatment course, suggesting a reduction in regional tumor hypoxia. <h3>Materials/Methods</h3> The study received ethics approval. Imaging was performed on a 1.5 T MRI-RT simulator (MRSim) and a 1.5 T MRL system. OE-MRI gas delivery was administered during a dynamic series: scans 1-25 (21% O₂), 26-70 (100% O₂) and 71-91 (21% O₂). A low-flow gas blender ensured 15 L/min flow via a high concentration mask. In patients, DCE-MRI was acquired after OE-MRI, at the 8^th dynamic measurement (gadoterate meglumine, 0.1 mol/kg at 3 ml/s). The protocol was initially run in 6 healthy volunteers, each imaged twice on the MRSim. Next, 8 patients with H&N carcinoma (15 lesions in total, including primary tumor and lymph nodes) were imaged on the MRSim 1-2 times pre-treatment and then during standard-of-care (C)RT at weeks 2 and/or 4. Finally, 3 additional patients were imaged on the MRL system. <h3>Results</h3> The technique developed in 6 volunteers identified the nasal conchae as a suitable reference tissue to confirm oxygen delivery, as signals changed between air and 100% O₂ breathing (all p<0.001). In the 8 patients recruited to date (table 1), we observed a significant reduction in median cohort pOxy-R proportion at week 2 (41% to 25%, p<0.01, N=14 lesions, 7 patients). pOxy-R proportion was reduced at week 4 (43% to 31%, p=0.06, N=5 lesions, 3 patients). Coefficient of variation (wCV), was found to be 24% (N=6 lesions). Technique feasibility was demonstrated on the MRL, with all tumors showing signal change between air and 100% O₂ breathing (all p<0.001). <h3>Conclusion</h3> OE-MRI can identify and map oxygen refractory regions in patients with H&N carcinoma and may detect cohort-wide hypoxia modification induced by (C)RT. The technique can also be translated onto an MRL system, suggesting the potential feasibility of using OE-MRI for online adaptive radiotherapy.