Preibisch Christine, Shi Kuangyu, Kluge Anne, Lukas Mathias, Wiestler Benedikt, Göttler Jens, Gempt Jens, Ringel Florian, Al Jaberi Mohamed, Schlegel Jürgen, Meyer Bernhard, Zimmer Claus, Pyka Thomas, Förster Stefan
Department of Diagnostic and Interventional Neuroradiology, Technische Universität München, Munich, Germany.
Clinic for Neurology, Technische Universität München, Munich, Germany.
NMR Biomed. 2017 Nov;30(11). doi: 10.1002/nbm.3775. Epub 2017 Aug 14.
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]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([ F]-FMISO). MR-rOEF was determined from separate measurements of T , T * 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]-FMISO-PET, besides the commonly used late uptake between 120 and 130 min ([ F]-FMISO ), we also analyzed the hypoxia specific uptake rate [ F]-FMISO-k , as obtained by pharmacokinetic modeling of dynamic uptake data. Since pharmacokinetic modeling of partially acquired dynamic [ F]-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]-FMISO concentrated in and around active tumor with disrupted blood-brain barrier, i.e. contrast enhancement in T -weighted MRI. Volume-of-interest-based correlations between MR-rOEF and [ F]-FMISO as well as [ F]-FMISO-k , and voxel-wise analyses in individual patients, yielded limited correlations, supporting the notion that [ F]-FMISO uptake, even after 2 h, might still be influenced by perfusion while [ F]-FMISO-k was severely hampered by noise. According to these results, vascular deoxygenation, as measured by MR-rOEF, and severe tissue hypoxia, as measured by [ F]-FMISO, show a poor spatial correspondence. Overall, the two methods appear to rather provide complementary than redundant information about high-grade glioma biology.
缺氧对癌症的预后和治疗反应起着重要作用。因此，缺氧成像将成为肿瘤恶性程度治疗前评估的一项有价值的工具。然而，目前尚无标准的、经过验证的临床应用技术。因此，我们对12例高级别胶质瘤患者进行了一项研究，直接比较了目前最有前景的两种技术，即基于磁共振成像的相对氧摄取分数（MR-rOEF）和PET缺氧标志物H-1-(3-[F]-氟-2-羟丙基)-2-硝基咪唑（[F]-FMISO）。MR-rOEF通过采用多参数方法分别测量T1、T2*和相对脑血容量（rCBV）来确定，以量化血氧水平依赖（BOLD）效应。关于[F]-FMISO-PET，除了常用的120至130分钟之间的延迟摄取（[F]-FMISO）外，我们还分析了通过动态摄取数据的药代动力学建模获得的缺氧特异性摄取率[F]-FMISO-k。由于部分获取的动态[F]-FMISO数据的药代动力学建模对低信噪比敏感，分析仅限于高摄取肿瘤区域。对脱氧和缺氧相关参数图的个体空间分析显示，高MR-rOEF值聚集在（水肿的）瘤周组织中，而高[F]-FMISO区域集中在血脑屏障破坏的活跃肿瘤内及其周围，即T1加权MRI中的对比增强区域。基于感兴趣区的MR-rOEF与[F]-FMISO以及[F]-FMISO-k之间的相关性，以及个体患者的体素分析，得出的相关性有限，支持了这样一种观点，即即使在2小时后，[F]-FMISO摄取仍可能受灌注影响，而[F]-FMISO-k则受到噪声的严重阻碍。根据这些结果，通过MR-rOEF测量的血管脱氧和通过[F]-FMISO测量的严重组织缺氧显示出较差的空间对应性。总体而言，这两种方法似乎提供的是关于高级别胶质瘤生物学的互补而非冗余信息。
