Complex relationship between changes in oxygenation status and changes in R*2: the case of insulin and NS-398, two inhibitors of oxygen consumption.

Insulin and NS-398 have been reported to inhibit oxygen consumption in experimental tumor models, thereby increasing oxygenation and radiosensitization. The aim of this work was to use MRI to study changes in murine FSaII tumor hemodynamics after administration of those oxygen consumption inhibitors. A multiple-echo gradient-echo (GRE) MRI sequence (4.7 T) was used to map changes in three factors: the GRE signal (at TE=20 ms), the parameter S0 (theoretical signal at TE=0 ms), and the relaxation rate R2. Perfusion maps were obtained by dynamic contrast-enhanced (DCE) MRI. Insulin caused a significant decrease in the tumor blood oxygen level-dependent (BOLD) signal over time. factor This was likely the result of decreased blood flow, since both S0 and the percentage of perfused tumor decreased as well. Tumor R2 did not change significantly in response to the treatments, which is surprising considering that other non-MRI techniques (electron paramagnetic resonance (EPR) oximetry and fiber-optic probes) have shown that tumor oxygenation increases after treatment. This suggests that metabolic changes associated with vasoactive challenges may have an unpredictable influence on blood saturation and R2. In conclusion, this study further emphasizes the fact that changes in BOLD signal and R2 in tumors do not depend uniquely on changes in oxygenation status.