Effect of carbogen on tumor oxygenation: Combined fluorine-19 and proton MRI measurements

Purpose: Blood oxygen level dependent (BOLD) contrast in magnetic resonance imaging (MRI) has been widely used for noninvasive evaluation of the effects of tumor-oxygenating agents. However, there have been few tests of the validity of this method. The goal of the present work was to use the T-1 of fluorine-19 in perfluorocarbon (PFC) emulsions as a "gold standard" for comparison with BOLD MRI. Methods and Materials: Rats bearing R3230AC tumors implanted in the hind limb were injected with an emulsion of perfluoro-15-crown-5-ether for 2-3 days before experiments, which ensured that the PFC emulsion concentrated in the tumors. We correlated changes in tumor oxygenation caused by carbogen inhalation measured by 1 H BOLD MRI with quantitative F-19 measurements. The F-19 spin-lattice relaxation rate R-1 (= 1/T-1) was measured to determine initial oxygen tension (pO(2)) in each image pixel containing the PFC, and changes in pO(2) during carbogen (95% O-2, 5% CO2) breathing. In a second carbogen breathing period, changes in water signal linewidth were measured using high spectral and spatial resolution imaging. F-19 and H-1 measurements were used to classify pixels as responders to carbogen (pixels where oxygen increased significantly) or nonresponders (no significant change in tumor oxygenation). Results: The F-19 and H-1 measurements agreed in 65% +/- 11% of pixels (n = 14). Agreement was even stronger among pixels where H-1 showed increased oxygenation; F-19 measurements agreed with 1H measurements in over 79% +/- 11% of these pixels. Similarly, there was strong agreement between the two modalities in pixels where F-19 reported no change in pO(2); H-1 also showed no changes in 76% +/- 18% of these pixels. Quantitative correlation of changes T-2* (DeltaT(2)*) in H-1 and changes R-1 (DeltaR(1)) in F-19 was weak during carbogen breathing, and averaged over the whole tumor was similar to0.40 for 14 experiments. However, the spatial patterns of H-1 and F-19 changes were qualitatively very similar. In hypoxic regions that were identified based on long F-19 T-1 (> 2.53 s), F-19 and 111 MRI agreed that carbogen had relatively weak effects. Conclusions: These results suggest that H-1 BOLD MRI reliably identifies increases in tumor pO(2) In hypoxic regions where increases in pO(2) are most desirable, carbogen was ineffective. The data suggest that F-19 and H-1 MRI can be used individually or in combination to guide the design of improved tumor-oxygenating agents. (C) 2002 Elsevier Science Inc.