de Godoy Laiz Laura, Lim Kheng Choon, Rajan Archith, Verma Gaurav, Hanaoka Mauro, O'Rourke Donald M, Lee John Y K, Desai Arati, Chawla Sanjeev, Mohan Suyash
Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Neuroradiology, Singapore General Hospital, Singapore 169609, Singapore.
Cancers (Basel). 2023 Sep 7;15(18):4453. doi: 10.3390/cancers15184453.
The isocitrate dehydrogenase () mutation has become one of the most important prognostic biomarkers in glioma management, indicating better treatment response and prognosis. mutations 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 (H-MRS) in identifying -mutant gliomas by detecting characteristic resonances of 2HG and its complex interplay with other clinically relevant metabolites.
Thirty-two patients with suspected infiltrative glioma underwent a single-voxel (SVS, n = 17) and/or single-slice-multivoxel (H-MRSI, n = 15) proton MR spectroscopy (H-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 determining mutational 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 between -mutant and -wild-type gliomas. Receiver operating characteristic (ROC) curve analyses were also performed.
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 as -mutant or -wildtype gliomas through SVS and 10/12 (83%) through H-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 predicting -mutant gliomas through the chi-squared test ( < 0.01). The -mutant gliomas also had a significantly higher NAA/Cr ratio (1.20 ± 0.09 vs. 0.75 ± 0.12 = 0.016) and lower Glx/Cr ratio (0.86 ± 0.078 vs. 1.88 ± 0.66; = 0.029) than those with wild-type gliomas. The areas under the ROC curves for NAA/Cr and Glx/Cr were 0.808 and 0.786, respectively.
Noninvasive optimized H-MRS may be useful in predicting mutational status and 2HG may serve as a valuable diagnostic and prognostic biomarker in patients with gliomas.
异柠檬酸脱氢酶（IDH）突变已成为胶质瘤治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突变赋予新功能活性，导致α-酮戊二酸（α-KG）转化为2-羟基戊二酸（2HG）。本研究的目的是通过检测2HG的特征共振及其与其他临床相关代谢物的复杂相互作用，探讨质子磁共振波谱（H-MRS）在识别IDH突变型胶质瘤中的临床潜力。
32例疑似浸润性胶质瘤患者在3T磁共振成像上接受了单体素（SVS，n = 17）和/或单层面多体素（H-MRSI，n = 15）质子磁共振波谱（H-MRS）序列，回波时间优化为97 ms。使用线性组合（LC）模型分析波谱数据。检测2HG时，克莱姆-拉奥下界（CRLB）值<40%被认为可接受，检测其他代谢物时<20%被认为可接受。随后从切除的肿瘤标本中进行免疫组织化学分析以确定IDH突变状态，并将结果与波谱数据结果进行比较。进行曼-惠特尼检验和卡方检验以确定IDH突变型和IDH野生型胶质瘤之间代谢物水平的差异。还进行了受试者操作特征（ROC）曲线分析。
8例患者的数据因波谱质量差或与肿瘤无关的病因被排除，最终对24例患者进行了数据分析。在这些病例中，通过SVS有9/12（75%）被正确鉴定为IDH突变型或IDH野生型胶质瘤，通过H-MRSI有10/12（83%）被正确鉴定，总体一致率为79%（19/24）。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%。通过卡方检验发现代谢物2HG在预测IDH突变型胶质瘤方面具有显著性（P < 0.01）。IDH突变型胶质瘤的NAA/Cr比值也显著高于IDH野生型胶质瘤（1.20 ± 0.09 vs. 0.75 ± 0.12；P = 0.016），Glx/Cr比值显著低于IDH野生型胶质瘤（0.86 ± 0.078 vs. 1.88 ± 0.66；P = 0.029）。NAA/Cr和Glx/Cr的ROC曲线下面积分别为0.808和0.786。
无创优化的H-MRS可能有助于预测IDH突变状态，2HG可能是胶质瘤患者有价值的诊断和预后生物标志物。
