Delineation techniques of tumor hypoxia volume with 18F-FMISO PET imaging

18F-fluoromisonidazole (18F-FMISO) is the most extensively used Positron Emission Tomography (PET) hypoxia biomarker. Uptake of 18F-FMISO by tumors provides a quantitative map of hypoxia, which can be used for dose escalation in radiotherapy. Several techniques have been developed to quantify and delineate the tumor hypoxia volumes such as tumor-to-blood ratio (TBR), tumor-to-normal tissue ratio (TNR) and compartmental modeling approaches. This study aims to report quantitative analyzes aiming at delineating hypoxia in tumors. Scanning protocols involved a 15 or 30 min dynamic scan followed by 10 min static scan at 2 h, 3 h and 4 h in order to allow accumulation of 18F-FMISO in the tumors. The quantitative analyzes were performed with spectral analysis (SA) and also with different threshold levels of TBR and TNR. TBR and TNR images were obtained by normalizing the measured images with respect to the concentration of 18F-FMISO in blood and in normal tissue, respectively, with multiple threshold levels of 1.2, 1.4, 2 and 2.5. A similarity index (SI) approach was chosen to quantitatively compare the TBR, TNR and SA images. The results showed that the TBR technique produced less spatially constrained volumes around the tumor than TNR with the same threshold level. TBR was found to be more dependent on the accuracy of the concentration in blood. SA images show the decomposed components of tumor as accumulative regions in the center of the tumor while the perfused regions were seen on the peripheries. The hypoxia defined with SA was more accurate since it is not sensitive to input function artefacts such as the partial volume effect. We found some similarities at specific thresholding levels and imaging times between TBR and TNR. In one subject, at 3 h, TBR at a levels of 1.4, 2 and 2.5 were respectively close to TNR at 1.4, 1.4 and 2, and TNR at 2 h and 3 h with a level of 1.2 presented a high similarity (SI > 85%). Despite these similarities, more interventions are expected for proper decisions on hypoxia localisation.