Methodology for quantifying interactions between perfusion evaluated by DCE-US and hypoxia throughout tumor growth.

The objective was to validate a combination of two new technologies to depict tumor physiology both temporally and spatially with dynamic contrast-enhanced sonography and an oximeter. Human cancer prostate tumors xenografted onto mice were followed for three weeks using dynamic contrast-enhanced ultrasonography (DCE-US) to detect tumor perfusion. Time intensity curves in linear data were quantified on four regions-of-interest (ROI, main tumor section and its anterior, central and posterior intra-tumoral areas) to extract three indices of perfusion. An oxygen sensor was guided by sonography to obtain accurate pO(2) measurements in the three predefined areas of tumors during their development. No impact on tumor growth of subsequent pO(2) probe insertion was detected. Among the four ROIs studied, the local central tumor showed significant perfusion and oxygenation variations throughout the experiment. A correlation was observed between local central tumor perfusion and pO(2), both of them decreasing through time (p = 0.0068; r = 0.66). The methodology which we developed demonstrated the potential of combining DCE-US with direct tissue pO(2) measurements, improving the description of complex intratumoral dynamic behavior.