Quantitative MRI assessment of VX2 tumour oxygenation changes in response to hyperoxia and hypercapnia

Magnetic resonance imaging (MRI) relaxation times provide indirect estimates of tissue O(2) for monitoring tumour oxygenation. This study provides insight into mechanisms underlying longitudinal (R(1) = 1/T(1)) and transverse effective (R(2)* = 1/T(2)*) relaxation rate changes during inhalation of 100% O(2) and 3%, 6% and 9% CO(2) (balanced O(2)) in a rabbit tumour model. Quantitative R(1), R(2)*, and dynamic contrast-enhanced (DCE) imaging was performed in six rabbits 12-23 days following implantation of VX2 carcinoma cells in the quadricep muscle. Invasive measurements of tissue partial pressure of O(2) (pO(2)) and perfusion were also performed, which revealed elevated pO(2) levels in all tumour regions for all hyperoxic gases compared to baseline (air) and reduced perfusion for carbogen. During 100% O(2) breathing, an R(1) increase and R(2)* decrease consistent with elevated pO(2) were observed within tumours. DCE-derived blood flow was weakly correlated with R(1) changes from air to 100% O(2). Further addition of CO(2) (carbogen) did not introduce considerable changes in MR relaxation rates, but a trend towards higher R(1) relative to breathing 100% O(2) was observed, while R(2)* changes were inconsistent. This observation supports the predominance of dissolved O(2) on R(1) sensitivity and demonstrates the value of R(1) over R(2)* for tissue oxygenation measures.