Noninvasive assessment of isocitrate dehydrogenase mutation status in cerebral gliomas by magnetic resonance spectroscopy in a clinical setting.
Noninvasive assessment of isocitrate dehydrogenase mutation status in cerebral gliomas by magnetic resonance spectroscopy in a clinical setting.
复制标题
DOI：
10.3171/2016.10.jns161793
复制
发表时间：
2018-02-01
影响因子：
4.1
通讯作者：
von Oettingen, Gorm
中科院分区：
文献类型：
--
作者：
Tietze, Anna;Choi, Changho;von Oettingen, Gorm
目的 异柠檬酸脱氢酶 (IDH) 基因突变对于脑胶质瘤具有诊断和预后意义。本研究的目的是评估使用最近描述的通过磁共振波谱 (MRS) 检测突变 IDH 酶的代谢产物 2-羟基戊二酸 (2HG) 的存在来确定 IDH 突变状态的方法的临床可行性。方法 通过将成像时间延长 6 分钟，作者能够将点分辨光谱 (PRESS) MRS 序列纳入其常规神经胶质瘤成像方案中。在使用这一修订方案的 35 名患者中，有 30 名患者的病变随后在组织学上被诊断为神经胶质瘤。其余 5 名患者中，1 名患有神经节细胞瘤，1 名患有原发性中枢神经系统淋巴瘤，3 名患有非肿瘤性病变。使用免疫组织化学和/或聚合酶链反应来检测切除的神经胶质瘤组织中IDH突变的存在。结果 2HG 体内 MRS 正确识别了 88.6% 患者的 IDH 突变状态。当使用 2 mM 2HG 作为阈值来区分 IDH 突变和野生型肿瘤时，敏感性和特异性分别为 89.5% 和 81.3%。两种 2HG 水平升高的胶质母细胞瘤没有可检测到的 IDH 突变，而在 2 个 IDH 突变的胶质瘤中，无法可靠地检测到 2HG。结论 通过 MRS 对假定神经胶质瘤的 IDH 突变状态进行无创测定，可以纳入常规诊断成像方案中，并可用于获取患者护理的附加信息。
OBJECTIVE Mutations in the isocitrate dehydrogenase (IDH) genes are of proven diagnostic and prognostic significance for cerebral gliomas. The objective of this study was to evaluate the clinical feasibility of using a recently described method for determining IDH mutation status by using magnetic resonance spectroscopy (MRS) to detect the presence of 2-hydroxyglutarate (2HG), the metabolic product of the mutant IDH enzyme. METHODS By extending imaging time by 6 minutes, the authors were able to include a point-resolved spectroscopy (PRESS) MRS sequence in their routine glioma imaging protocol. In 30 of 35 patients for whom this revised protocol was used the lesions were subsequently diagnosed histologically as gliomas. Of the remaining 5 patients, 1 had a gangliocytoma, 1 had a primary CNS lymphoma, and 3 had nonneoplastic lesions. Immunohistochemistry and/or polymerase chain reaction were used to detect the presence of IDH mutations in the glioma tissue resected. RESULTS In vivo MRS for 2HG correctly identified the IDH mutational status in 88.6% of patients. The sensitivity and specificity was 89.5% and 81.3%, respectively, when using 2 mM 2HG as threshold to discriminate IDH-mutated from wildtype tumors. Two glioblastomas that had elevated 2HG levels did not have detectable IDH mutations, and in 2 IDH-mutated gliomas 2HG was not reliably detectable. CONCLUSIONS The noninvasive determination of the IDH mutation status of a presumed glioma by means of MRS may be incorporated into a routine diagnostic imaging protocol and can be used to obtain additional information for patient care.