Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study

Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre-therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high-grade glioma, where we directly compared the two currently most promising techniques, namely the MR-based relative oxygen extraction fraction (MR-rOEF) and the PET hypoxia marker H-1-(3-[F-18]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([F-18]-FMISO). MR-rOEF was determined from separate measurements of T-2, T-2* and relative cerebral blood volume (rCBV) employing a multi-parametric approach for quantification of the blood-oxygenation-level-dependent (BOLD) effect. With respect to [F-18]-FMISO-PET, besides the commonly used late uptake between 120 and 130 min ([F-18]-FMISO120-130 min), we also analyzed the hypoxia specific uptake rate [F-18]-FMISO-k(3), as obtained by pharmacokinetic modeling of dynamic uptake data. Since pharmacokinetic modeling of partially acquired dynamic [F-18]-FMISO data was sensitive to a low signal-to-noise-ratio, analysis was restricted to high-uptake tumor regions. Individual spatial analyses of deoxygenation and hypoxia-related parameter maps revealed that high MR-rOEF values clustered in (edematous) peritumoral tissue, while areas with high [F-18]-FMISO120-130 min concentrated in and around active tumor with disrupted blood-brain barrier, i.e. contrast enhancement in T-1-weighted MRI. Volume-of-interest-based correlations between MR-rOEF and [F-18]-FMISO120-130 min as well as [F-18]-FMISO-k(3), and voxel-wise analyses in individual patients, yielded limited correlations, supporting the notion that [F-18]-FMISO uptake, even after 2 h, might still be influenced by perfusion while [F-18]-FMISO-k(3) was severely hampered by noise. According to these results, vascular deoxygenation, as measured by MR-rOEF, and severe tissue hypoxia, as measured by [F-18]-FMISO, show a poor spatial correspondence. Overall, the two methods appear to rather provide complementary than redundant information about high-grade glioma biology.