Monitoring of tumor oxygenation variations using non invasive imaging based on lipid oxygen dependent relaxation in magnetic resonance : preclinical and clinical applications

Quantitative follow-up of changes in tumor oxygenation can find relevant applications in radiation therapy planning since oxygen is a critical determinant of tumor radiation response, both in terms of inter and intra-tumor heterogeneity. Variations in T1 and T2* are potentially valuable MRI parameters able to follow changes in oxygenation. T2* is sensitive to the relative Hb/HbO2 ratio in vessels and provides information on vascular oxygenation, whereas T1 is sensitive to dissolved oxygen in tissues which acts as a T1-shortening paramagnetic endogenous contrast agent. The MOBILE technique is based on the measurement of the longitudinal relaxation rate of lipids protons, in order to exploit the higher solubility of oxygen in lipids than in water in an attempt to enhance the sensitivity of the T1 mapping. In the preclinical setting on a 11.7T MRI system, the MOBILE technique demonstrated: (i) its ability to monitor muscle, liver, brain and tumor tissues changes in oxygenation; (ii) its quantitative properties, by benchmarking the technique with Electron Paramagnetic Resonance (EPR) oximetry, and (iii) its ability to probe changes in the tumor microenvironment induced by the administration of a vascular disrupting agent, in comparison with Dynamic Contrast Enhanced (DCE) MRI. In the clinical setting, MOBILE was implemented on a 3T MRI system to map oxygenation in patients with strokes, gliomas, or in healthy brains, and successfully highlighted differences in oxygenation status in those paradigmatic situations. However, several limitations of the method have been identified both in the preclinical and clinical settings. Further developments in the acquisition sequence and data processing are discussed that should lead to an improvement of the methodology.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201