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Effect of carbogen on tumor oxygenation: combined fluorine-19 and proton MRI measurementsby: X. Fan
International Journal of Radiation Oncology*Biology*Physics, Vol. 54, No. 4. (15 November 2002), pp. 1202-1209.
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Abstract: 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. : 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 19 F measurements. The 19 F 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% CO 2 ) breathing. In a second carbogen breathing period, changes in water signal linewidth were measured using high spectral and spatial resolution imaging. 19 F and 1 H measurements were used to classify pixels as responders to carbogen (pixels where oxygen increased significantly) or nonresponders (no significant change in tumor oxygenation). : The 19 F and 1 H measurements agreed in 65% ± 11% of pixels ( n = 14). Agreement was even stronger among pixels where 1 H showed increased oxygenation; 19 F measurements agreed with 1 H measurements in over 79% ± 11% of these pixels. Similarly, there was strong agreement between the two modalities in pixels where 19 F reported no change in pO 2 ; 1 H also showed no changes in 76% ± 18% of these pixels. Quantitative correlation of changes T 2 * (ΔT 2 *) in 1 H and changes R 1 (ΔR 1 ) in 19 F was weak during carbogen breathing, and averaged over the whole tumor was 0.40 for 14 experiments. However, the spatial patterns of 1 H and 19 F changes were qualitatively very similar. In hypoxic regions that were identified based on long 19 F T 1 (>2.53 s), 19 F and 1 H MRI agreed that carbogen had relatively weak effects. : These results suggest that 1 H 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 19 F and 1 H MRI can be used individually or in combination to guide the design of improved tumor-oxygenating agents.
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