Fan Xiaobing, River Jonathan N, Zamora Marta, Al-Hallaq Hania A, Karczmar Gregory S
Department of Radiology, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
Int J Radiat Oncol Biol Phys. 2002 Nov 15;54(4):1202-9. doi: 10.1016/s0360-3016(02)03035-3.
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. MATHODS 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 (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)* (DeltaT(2)*) in (1)H and changes R(1) (DeltaR(1)) in (19)F was weak during carbogen breathing, and averaged over the whole tumor was approximately 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.
磁共振成像（MRI）中的血氧水平依赖（BOLD）对比已被广泛用于无创评估肿瘤充氧剂的效果。然而，对该方法有效性的测试却很少。本研究的目的是将全氟化碳（PFC）乳剂中氟 - 19的T(1)作为“金标准”，与BOLD MRI进行比较。
将R3230AC肿瘤植入后肢的大鼠在实验前2 - 3天注射全氟 - 15 - 冠 - 5 - 醚乳剂，以确保PFC乳剂集中在肿瘤中。我们将通过氢质子BOLD MRI测量的吸入混合气（95% O₂，5% CO₂）引起的肿瘤氧合变化与氟 - 19的定量测量结果相关联。测量氟 - 19的自旋晶格弛豫率R(1)（= 1/T(1)），以确定每个含有PFC的图像像素中的初始氧分压（pO₂），以及在吸入混合气期间pO₂的变化。在第二个吸入混合气期间，使用高光谱和空间分辨率成像测量水信号线宽的变化。氟 - 19和氢质子测量用于将像素分类为对吸入混合气有反应的像素（氧含量显著增加的像素）或无反应的像素（肿瘤氧合无显著变化）。
氟 - 19和氢质子测量在65% ± 11%的像素中一致（n = 14）。在氢质子显示氧合增加的像素中，一致性更强；氟 - 19测量与氢质子测量在超过79% ± 11%的这些像素中一致。同样，在氟 - 19报告pO₂无变化的像素中，两种模式之间也有很强的一致性；氢质子在这些像素中的76% ± 18%中也显示无变化。在吸入混合气期间，氢质子中T(2)（ΔT(2)）的变化与氟 - 19中R(1)（ΔR(1)）的变化之间的定量相关性较弱，在14个实验中，整个肿瘤的平均值约为0.40。然而，氢质子和氟 - 19变化的空间模式在定性上非常相似。在基于长氟 - 19 T(1)（>2.53 s）确定的缺氧区域，氟 - 19和氢质子MRI一致认为吸入混合气的效果相对较弱。
这些结果表明，氢质子BOLD MRI能够可靠地识别肿瘤pO₂的增加。在最需要增加pO₂的缺氧区域，吸入混合气无效。数据表明，氟 - 19和氢质子MRI可单独使用或联合使用，以指导改进肿瘤充氧剂的设计。
