Purpose: The isocitrate dehydrogenase (IDH) mutation has become one of the most important prognostic biomarkers in glioma management, indicating better treatment response and prognosis.IDHmutations confer neomorphic activity leading to the conversion of alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2HG). The purpose of this study was to investigate the clinical potential of proton MR spectroscopy (1H-MRS) in identifyingIDH-mutant gliomas by detecting characteristic resonances of 2HG and its complex interplay with other clinically relevant metabolites. Materials and Methods: Thirty-two patients with suspected infiltrative glioma underwent a single-voxel (SVS, n = 17) and/or single-slice-multivoxel (1H-MRSI, n = 15) proton MR spectroscopy (1H-MRS) sequence with an optimized echo-time (97 ms) on 3T-MRI. Spectroscopy data were analyzed using the linear combination (LC) model. Cramér–Rao lower bound (CRLB) values of <40% were considered acceptable for detecting 2HG and <20% for other metabolites. Immunohistochemical analyses for determiningIDHmutational status were subsequently performed from resected tumor specimens and findings were compared with the results from spectral data. Mann–Whitney and chi-squared tests were performed to ascertain differences in metabolite levels betweenIDH-mutant andIDH-wild-type gliomas. Receiver operating characteristic (ROC) curve analyses were also performed. Results: Data from eight cases were excluded due to poor spectral quality or non-tumor-related etiology, and final data analyses were performed from 24 cases. Of these cases, 9/12 (75%) were correctly identified asIDH-mutant orIDH-wildtype gliomas through SVS and 10/12 (83%) through1H-MRSI with an overall concordance rate of 79% (19/24). The sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 77%, 86%, and 70%, respectively. The metabolite 2HG was found to be significant in predictingIDH-mutant gliomas through the chi-squared test (p< 0.01). TheIDH-mutant gliomas also had a significantly higher NAA/Cr ratio (1.20 ± 0.09 vs. 0.75 ± 0.12p= 0.016) and lower Glx/Cr ratio (0.86 ± 0.078 vs. 1.88 ± 0.66;p= 0.029) than those withIDHwild-type gliomas. The areas under the ROC curves for NAA/Cr and Glx/Cr were 0.808 and 0.786, respectively. Conclusions: Noninvasive optimized1H-MRS may be useful in predictingIDHmutational status and 2HG may serve as a valuable diagnostic and prognostic biomarker in patients with gliomas
目的：异柠檬酸脱氢酶（IDH）突变已成为胶质瘤诊疗中最重要的预后生物标志物之一，提示更好的治疗反应和预后。IDH突变赋予肿瘤细胞新形态活性，导致α-酮戊二酸（α-KG）转化为2-羟基戊二酸（2HG）。本研究旨在探讨质子磁共振波谱（1H-MRS）通过检测2HG特征性共振峰及其与其他临床相关代谢物的复杂相互作用，在识别IDH突变型胶质瘤中的临床应用潜力。材料与方法：32例疑似浸润性胶质瘤患者接受3T-MRI扫描，采用优化回波时间（97 ms）进行单体素（SVS，n=17）和/或单层多体素（1H-MRSI，n=15）质子磁共振波谱序列采集。使用线性组合模型分析波谱数据，2HG的克拉美-罗下界值<40%、其他代谢物<20%被视为可接受范围。对切除肿瘤标本进行免疫组化分析确定IDH突变状态，并将结果与波谱数据进行比对。采用曼-惠特尼检验和卡方检验分析IDH突变型与野生型胶质瘤代谢物水平差异，同时进行受试者工作特征曲线分析。结果：8例因波谱质量不佳或非肿瘤性病因被排除，最终对24例数据进行分析。通过SVS正确识别IDH突变型/野生型胶质瘤9/12例（75%），通过1H-MRSI正确识别10/12例（83%），总体符合率达79%（19/24）。检测的敏感性、特异性、阳性预测值和阴性预测值分别为80%、77%、86%和70%。卡方检验显示2HG对预测IDH突变型胶质瘤具有显著意义（p<0.01）。与IDH野生型胶质瘤相比，突变型肿瘤具有显著更高的NAA/Cr比值（1.20±0.09 vs. 0.75±0.12，p=0.016）和更低的Glx/Cr比值（0.86±0.078 vs. 1.88±0.66，p=0.029）。NAA/Cr与Glx/Cr的ROC曲线下面积分别为0.808和0.786。结论：无创优化的1H-MRS技术可用于预测IDH突变状态，2HG可能成为胶质瘤患者有价值的诊断和预后生物标志物。
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