Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery
Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery
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DOI：
10.1073/pnas.1404724111
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发表时间：
2014-07-29
影响因子：
11.1
通讯作者：
Agar, Nathalie Y. R.
中科院分区：
文献类型：
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作者：
Santagata, Sandro;Eberlin, Livia S.;Agar, Nathalie Y. R.
对于许多手术中的决定，外科医生依赖于冰冻切片病理，这是150多年前发展起来的一项技术。需要能够在手术时对组织样本进行快速分子表征的技术创新。在这里，我们使用解吸电喷雾电离(DESI)MS，在不需要复杂或耗时的准备的情况下，在环境条件下从手术切除的胶质瘤组织切片中快速检测肿瘤代谢物2-羟基戊二酸(2-HG)。使用DESI MS，我们可以在几分钟内以高灵敏度和高特异度识别异柠檬酸脱氢酶1突变肿瘤，立即提供关键的诊断、预后和预测信息。DESI MS成像组织切片显示，2-HG信号与肿瘤区域重叠，2-HG水平与肿瘤内容物相关，从而指示肿瘤边缘。将2-HG信号映射到肿瘤的3D MRI重建上，可以整合分子和放射学信息，以增强临床决策。我们还验证了该方法及其在手术室中的部署：我们在高级多模式图像引导手术(AMIGO)套件中安装了质谱仪，并演示了脑外科手术过程中手术组织的分子分析。这项工作表明，代谢成像MS可以改变外科护理的许多方面。
For many intraoperative decisions surgeons depend on frozen section pathology, a technique developed over 150 y ago. Technical innovations that permit rapid molecular characterization of tissue samples at the time of surgery are needed. Here, using desorption electrospray ionization (DESI) MS, we rapidly detect the tumor metabolite 2-hydroxyglutarate (2-HG) from tissue sections of surgically resected gliomas, under ambient conditions and without complex or time-consuming preparation. With DESI MS, we identify isocitrate dehydrogenase 1-mutant tumors with both high sensitivity and specificity within minutes, immediately providing critical diagnostic, prognostic, and predictive information. Imaging tissue sections with DESI MS shows that the 2-HG signal overlaps with areas of tumor and that 2-HG levels correlate with tumor content, thereby indicating tumor margins. Mapping the 2-HG signal onto 3D MRI reconstructions of tumors allows the integration of molecular and radiologic information for enhanced clinical decision making. We also validate the methodology and its deployment in the operating room: We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite and demonstrate the molecular analysis of surgical tissue during brain surgery. This work indicates that metabolite-imaging MS could transform many aspects of surgical care.