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使用频谱编辑磁共振波谱术术前测定胶质瘤中的异柠檬酸脱氢酶突变:一项前瞻性研究

Preoperative Determination of Isocitrate Dehydrogenase Mutation in Gliomas Using Spectral Editing MRS: A Prospective Study.

作者信息

Nguyen Thanh B, Melkus Gerd, Taccone Michael, Moldovan Ioana D, Ghinda Diana, Gotfrit Ryan, Torres Carlos H, Zakhari Nader, Chakraborty Santanu, Woulfe John, Jansen Gerard, McInnes Matthew Df, Thornhill Rebecca E, Cameron Ian, AlKherayf Fahad

机构信息

Department of Radiology, The Ottawa Hospital, Ottawa, Ontario, Canada.

University of Ottawa, Ottawa, Ontario, Canada.

出版信息

J Magn Reson Imaging. 2021 Feb;53(2):416-426. doi: 10.1002/jmri.27366. Epub 2020 Sep 17.

DOI:10.1002/jmri.27366
PMID:32940938
Abstract

BACKGROUND

The edited magnetic resonance spectroscopy (MRS) technique has not yet been formally evaluated for the in vivo detection of 2-hydroxyglutarate (2-HG) in patients with gliomas of various grades.

PURPOSE

To evaluate the diagnostic accuracy of edited MRS in the preoperative identification of the isocitrate dehydrogenase (IDH) mutation status in patients with gliomas.

STUDY TYPE

Prospective.

POPULATION

Fifty-eight subjects (31 glioblastomas, 27 grade II and III gliomas).

FIELD STRENGTH/SEQUENCE: Mescher-Garwood (MEGA)-PRESS and routine clinical brain tumor MR sequences were used at 3T.

ASSESSMENT

Data were analyzed using an advanced method for accurate, robust, and efficient spectral fitting (AMARES) from jMRUI software. The amplitudes of the 2-HG, N-acetyl-aspartate (NAA), choline (Cho), and creatine/phosphocreatine (Cr) resonances were calculated with their associated Cramer-Rao lower bound (CRLB). The IDH1 R132H mutation status was assessed by immunohistochemistry for all patients. Patients with grades II and III gliomas with negative immunohistochemistry underwent DNA sequencing to further interrogate IDH mutation status.

STATISTICAL TEST

The differences in 2-HG amplitudes, 2-HG/NAA, 2-HG/Cho, and 2-HG/Cr between IDH-mutant and IDH-wildtype gliomas were assessed using Mann-Whitney U-tests. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of each parameter.

RESULTS

The 2-HG amplitudes, 2-HG/NAA, and 2-HG/Cho were higher for IDH-mutant gliomas than IDH-wildtype gliomas (P < 0.007). Using a CRLB threshold <30%, a 2-HG cutoff greater than 0 had a sensitivity of 80% (95% confidence interval [CI]: 52-96%) and a specificity of 81% (95% CI: 54-96%) in identifying IDH-mutant gliomas. In the subset of patients with grades II and III gliomas, the sensitivity was 80% (95% CI: 52-96%) and specificity was 100% (95% CI: 40-100%). Among 2-HG ratios, the highest AUC for the identification of IDH mutant status was achieved using the 2-HG/NAA (AUC = 0.8, 95% CI 0.67-.89).

DATA CONCLUSION

Preoperative edited MRS appears to be able to help identify IDH-mutant gliomas with high specificity. Level of Evidence 1 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:416-426.

摘要

背景

编辑磁共振波谱(MRS)技术尚未针对不同级别胶质瘤患者体内2-羟基戊二酸(2-HG)的检测进行正式评估。

目的

评估编辑MRS在术前识别胶质瘤患者异柠檬酸脱氢酶(IDH)突变状态的诊断准确性。

研究类型

前瞻性研究。

研究对象

58名受试者(31例胶质母细胞瘤,27例II级和III级胶质瘤)。

场强/序列:在3T条件下使用Mescher-Garwood(MEGA)-PRESS序列和常规临床脑肿瘤MR序列。

评估

使用jMRUI软件中的先进方法进行准确、稳健和高效的谱拟合(AMARES)分析数据。计算2-HG、N-乙酰天门冬氨酸(NAA)、胆碱(Cho)和肌酸/磷酸肌酸(Cr)共振峰幅度及其相关的克拉美-罗下限(CRLB)。通过免疫组织化学评估所有患者的IDH1 R132H突变状态。免疫组织化学阴性的II级和III级胶质瘤患者进行DNA测序以进一步确定IDH突变状态。

统计学检验

采用Mann-Whitney U检验评估IDH突变型和IDH野生型胶质瘤之间2-HG幅度、2-HG/NAA、2-HG/Cho和2-HG/Cr的差异。进行受试者操作特征曲线分析以评估各参数的诊断准确性。

结果

IDH突变型胶质瘤的2-HG幅度、2-HG/NAA和2-HG/Cho高于IDH野生型胶质瘤(P < 0.007)。使用CRLB阈值<30%,2-HG截断值大于0在识别IDH突变型胶质瘤时的灵敏度为80%(95%置信区间[CI]:52-96%),特异性为81%(95% CI:54-96%)。在II级和III级胶质瘤患者亚组中,灵敏度为80%(95% CI:52-96%),特异性为100%(95% CI:40-100%)。在2-HG比值中,使用2-HG/NAA识别IDH突变状态时的曲线下面积最高(AUC = 0.8,95% CI 0.67-.89)。

数据结论

术前编辑MRS似乎能够以高特异性帮助识别IDH突变型胶质瘤。证据水平1 技术效能2期 J.MAGN.RESON.IMAGING 2021;53:416-426。

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