Assessment of vascular reactivity in rat brain glioma by measuring regional blood volume during graded hypoxic hypoxia

While morphological and molecular events during angiogenesis in brain glioma have been extensively studied, the functional properties of tumour vessels have yet received little attention. We have determined changes in regional blood volume (BV) during graded hypoxic hypoxia using susceptibility contrast magnetic resonance imaging in a model of rat brain glioma. Nine anaesthetised and ventilated rats with C6 glioma were subjected to incremental reduction in the fraction of inspired oxygen (FiO2): 0.35, 0.25, 0.15, 0.12, 0.10 and reoxygenation to 0.35. At each episode, BV was determined in peritumoral, intratumoral and contralateral regions. Baseline BV values (FiO2 of 0.35) were higher in peritumoral than in the contralateral and intratumoral regions. Progressive hypoxia resulted in a graded increase in BV in contralateral and peritumoral regions. At FiO2 of 0.10, BV increases were comparable between these two regions: 49±22% (s.d.) and 28±17% with respect of control values, respectively. These BV changes reversed during the reoxygenation episode. By contrast, the intratumoral region had a significant increase in BV at FiO2 of 0.10 only, with no evidence of return to the basal value during reoxygenation. Immunohistochemical staining of α-smooth muscle actin confirmed reactivity of vessels in the peritumoral region. Our findings indicate that peritumoral vessels present a vascular reactivity to hypoxia, which is comparable to that of nontumoral vessels. A method is thus available for noninvasively demonstrating whether any particular vascular modifying strategy results in the desired outcome in terms of tumour blood volume changes.