FMISO-PET-derived brain oxygen tension maps: application to glioblastoma and less aggressive gliomas

Quantitative imaging modalities for the analysis of hypoxia in brain tumors are lacking. The objective of this study was to generate absolute maps of tissue p_tO₂ from [¹⁸F]-FMISO images in glioblastoma and less aggressive glioma patients in order to quantitatively assess tumor hypoxia. An ancillary objective was to compare estimated p_tO₂ values to other biomarkers: perfusion weighted imaging (PWI) and tumor metabolism obtained from ¹H-MR mono-voxel spectroscopy (MRS). Ten patients with glioblastoma (GBM) and three patients with less aggressive glioma (nGBM) were enrolled. All patients had [¹⁸F]-FMISO and multiparametric MRI (anatomic, PWI, MRS) scans. A non-linear regression was performed to generate p_tO₂ maps based on normal appearing gray (NAGM) and white matter (NAWM) for each patient. As expected, a marked [¹⁸F]-FMISO uptake was observed in GBM patients. The p_tO₂ based on patient specific calculations was notably low in this group (4.8 ± 1.9 mmHg, p < 0.001) compared to all other groups (nGBM, NAGM and NAWM). The rCBV was increased in GBM (1.4 ± 0.2 when compared to nGBM tumors 0.8 ± 0.4). Lactate (and lipid) concentration increased in GBM (27.8 ± 13.8%) relative to nGBM (p < 0.01). Linear, nonlinear and ROC curve analyses between p_tO₂ maps, PWI-derived rCBV maps and MRS-derived lipid and lactate concentration strengthens the robustness of our approaches.