Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study
Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study
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DOI：
10.1002/nbm.3775
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发表时间：
2017-11-01
影响因子：
2.9
通讯作者：
Foerster, Stefan
中科院分区：
文献类型：
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作者：
Preibisch, Christine;Shi, Kuangyu;Foerster, Stefan
缺氧对肿瘤的预后和治疗反应起着重要的作用。因此，缺氧成像将是治疗前评估肿瘤恶性的一种有价值的工具。然而，目前还没有临床应用的标准验证技术。因此，我们在12例高级别胶质瘤患者中进行了一项研究，我们直接比较了两种目前最有前途的技术，即基于mr的相对氧提取分数（MR-rOEF）和PET缺氧标记物H-1-（3-[F-18]-氟-2-羟丙基）-2-硝基咪唑（[F-18]- fmiso）。MR-rOEF通过单独测量T-2、T-2*和相对脑血容量（rCBV）来确定，采用多参数方法量化血氧水平依赖性（BOLD）效应。对于[F-18]-FMISO-PET，除了常用的后期摄取时间为120-130 min （[F-18]-FMISO120-130 min）外，我们还通过对动态摄取数据的药代动力学建模，分析了缺氧特定摄取速率[F-18]-FMISO-k(3)。由于部分获取的动态[F-18]-FMISO数据的药代动力学建模对低信噪比敏感，因此分析仅限于高摄取肿瘤区域。脱氧和缺氧相关参数图的个体空间分析显示，高MR-rOEF值集中在（水肿）肿瘤周围组织，而高[F-18]-FMISO120-130 min区域集中在活动性肿瘤内和周围，血脑屏障被破坏，即t -1加权MRI的对比增强。MR-rOEF与[F-18]-FMISO120-130分钟以及[F-18]-FMISO-k(3)之间基于兴趣体积的相关性，以及个体患者的体素分析，得出了有限的相关性，支持了[F-18]-FMISO摄取即使在2小时后仍可能受到灌注的影响，而[F-18]-FMISO-k(3)受到噪声的严重阻碍的观点。根据这些结果，MR-rOEF测量的血管缺氧和[F-18]-FMISO测量的严重组织缺氧在空间上的对应关系很差。总的来说，这两种方法似乎提供了关于高级胶质瘤生物学的补充而不是多余的信息。
Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre-therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high-grade glioma, where we directly compared the two currently most promising techniques, namely the MR-based relative oxygen extraction fraction (MR-rOEF) and the PET hypoxia marker H-1-(3-[F-18]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([F-18]-FMISO). MR-rOEF was determined from separate measurements of T-2, T-2* and relative cerebral blood volume (rCBV) employing a multi-parametric approach for quantification of the blood-oxygenation-level-dependent (BOLD) effect. With respect to [F-18]-FMISO-PET, besides the commonly used late uptake between 120 and 130 min ([F-18]-FMISO120-130 min), we also analyzed the hypoxia specific uptake rate [F-18]-FMISO-k(3), as obtained by pharmacokinetic modeling of dynamic uptake data. Since pharmacokinetic modeling of partially acquired dynamic [F-18]-FMISO data was sensitive to a low signal-to-noise-ratio, analysis was restricted to high-uptake tumor regions. Individual spatial analyses of deoxygenation and hypoxia-related parameter maps revealed that high MR-rOEF values clustered in (edematous) peritumoral tissue, while areas with high [F-18]-FMISO120-130 min concentrated in and around active tumor with disrupted blood-brain barrier, i.e. contrast enhancement in T-1-weighted MRI. Volume-of-interest-based correlations between MR-rOEF and [F-18]-FMISO120-130 min as well as [F-18]-FMISO-k(3), and voxel-wise analyses in individual patients, yielded limited correlations, supporting the notion that [F-18]-FMISO uptake, even after 2 h, might still be influenced by perfusion while [F-18]-FMISO-k(3) was severely hampered by noise. According to these results, vascular deoxygenation, as measured by MR-rOEF, and severe tissue hypoxia, as measured by [F-18]-FMISO, show a poor spatial correspondence. Overall, the two methods appear to rather provide complementary than redundant information about high-grade glioma biology.