Department of Chemistry and Bindley Biosciences Center, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907-1393, USA.
Department of Neurological Surgery, Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Anal Bioanal Chem. 2019 Dec;411(30):7929-7933. doi: 10.1007/s00216-019-02198-y. Epub 2019 Nov 21.
Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. Graphical abstract.
脑肿瘤患者异柠檬酸脱氢酶（IDH）突变状态的知识可以为脑外科手术中的决策提供依据。然而，病理检查无法在手术过程中提供此类信息。本文首次描述了将微型质谱仪（MS）应用于术中检测脑肿瘤 IDH 突变状态。该仪器经过改装，可在手术室中使用。对致癌代谢物 2-羟基戊二酸和不参与 IDH 突变的参考代谢物谷氨酸进行串联 MS，测量碎片离子强度比以计算 IDH 突变评分，用于区分 IDH 突变型和野生型组织。对 13 名患者的 25 个活检样本进行分析的结果表明，可靠地确定了 IDH 突变状态（使用 Kruskal-Wallis 非参数检验，p=0.0001）。这种微型质谱仪的应用具有体积小、功耗和噪声水平低的特点，是一种简单且具有成本效益的平台，可用于重要的术中测量。
