JESSENIUS-Diagnostic Center, Nitra, Slovakia.
Medical Faculty, Comenius University in Bratislava, Bratislava, Slovakia.
MAGMA. 2022 Feb;35(1):45-52. doi: 10.1007/s10334-021-00989-y. Epub 2022 Jan 5.
Oncometabolite D-2-hydroxyglutarate (2HG) is pooled in isocitrate dehydrogenase (IDH)-mutant glioma cells. Detecting 2HG by MR spectroscopy (MRS) has been proven viable in the last decade but has not entirely found its way into the clinical routine. This study aimed to explore the adoption of 2HG MRS while acknowledging factors that influence its performance in the clinical environment.
Thirty-nine MR spectra were acquired and reported prospectively in patients with suspected glioma using a 3 T system with Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence utilizing averaged free induction decay (FID) signals. Postprocessing and evaluation of spectra were performed with jMRUI and LCModel. 2HG concentration estimates, 2HG/Cr ratio, together with quality measures, including Cramér-Rao lower bounds (CRLBs), full-width at half-maximum (FWHM) values, and signal-to-noise ratio (SNR) were calculated using LCModel. Immunohistochemistry and genomic analysis results used as a ground truth were available for 15 patients.
The threshold for test positivity was set according to the ROC curve at 1 mM. Calculated sensitivity was 57.14% (95% CI 0.20-0.88), specificity 87.5% (95% CI 0.46-0.99), positive predictive value 80%, and negative predictive value 70%. Overall diagnostic accuracy was 73.33% (95% CI 0.45-0.92). The 2HG/Cr ratio with the cutoff value 0.085 significantly improved sensitivity and overall diagnostic accuracy [85.71%, 95% CI 0.42-1.00 and 86.67%, (95% CI 0.60-0.98), respectively].
Multiple factors compromising spectral quality in the clinical adoption of edited 2HG MRS resulted in diminished sensitivity but clinically acceptable specificity. Furthermore, the 2HG/Cr ratio performs better than the sole 2HG concentration estimate in the pre-operative setting.
代谢物 D-2-羟基戊二酸(2HG)在异柠檬酸脱氢酶(IDH)突变型神经胶质瘤细胞中积累。在过去的十年中,通过磁共振波谱(MRS)检测 2HG 已被证明是可行的,但尚未完全纳入临床常规。本研究旨在探讨在承认影响其在临床环境中性能的因素的情况下采用 2HG MRS。
使用 3T 系统和 Mescher-Garwood 点分辨波谱(MEGA-PRESS)序列采集并前瞻性报告了 39 例疑似神经胶质瘤患者的 MR 光谱,该序列利用平均自由感应衰减(FID)信号进行。使用 jMRUI 和 LCModel 对光谱进行后处理和评估。使用 LCModel 计算 2HG 浓度估计值、2HG/Cr 比值以及质量指标,包括克拉默-劳下限(CRLB)、半峰全宽(FWHM)值和信噪比(SNR)。共有 15 例患者的免疫组织化学和基因组分析结果可用作基准。
根据 ROC 曲线将测试阳性的阈值设定为 1mM。计算的灵敏度为 57.14%(95%CI 0.20-0.88),特异性为 87.5%(95%CI 0.46-0.99),阳性预测值为 80%,阴性预测值为 70%。总体诊断准确性为 73.33%(95%CI 0.45-0.92)。截断值为 0.085 的 2HG/Cr 比值显著提高了灵敏度和总体诊断准确性[85.71%,95%CI 0.42-1.00 和 86.67%,(95%CI 0.60-0.98)]。
编辑 2HG MRS 在临床应用中多种因素影响光谱质量,导致灵敏度降低,但特异性可接受。此外,在术前环境中,2HG/Cr 比值的性能优于单独的 2HG 浓度估计值。