Alcicek Seyma, Simicic Dunja, Blair Lindsay, Saint-Germain Max, Zöllner Helge J, Davies-Jenkins Christopher W, Holdhoff Matthias, Laterra John, Bettegowda Chetan, Schreck Karisa C, Lin Doris D, Barker Peter B, Kamson David O, Oeltzschner Georg
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany.
medRxiv. 2025 Apr 1:2025.03.31.25324828. doi: 10.1101/2025.03.31.25324828.
In-vivo magnetic resonance spectroscopy (MRS) of 2-hydroxyglutarate (2HG) may provide diagnostic and monitoring biomarkers in isocitrate dehydrogenase (IDH)-mutated glioma. A previous meta-analysis has shown good diagnostic accuracy of TE-optimized PRESS for IDH-mutated glioma, but most studies feature IDH-wildtype glioma as a comparison. However, when considering newly identified brain lesions that may mimic glioma, full characterization of its diagnostic utility should also consider the accuracy of 2HG measurement in non-tumor tissue. Therefore, we tested how well TE-optimized 2HG levels distinguish between IDH-mutated glioma and non-tumor tissue, in this case, normal-appearing brain. We further examined the impact of different spectral modeling strategies (baseline stiffness, macromolecule inclusion, and basis set composition).
48 patients with diagnosed/suspected IDH-mutated glioma were enrolled. 3T MRS data were acquired from tumor and contralateral non-tumor tissue with PRESS localization (TE = 97 ms, optimized for 2HG detection) and analyzed with 'LCModel' software. Receiver operating characteristic analysis evaluated 2HG estimates' ability to distinguish IDH-mutated glioma from non-tumor brain tissue. Modeling interactions between 2HG and other metabolites were evaluated to identify reasons for potential false-positive 2HG detection.
TE-optimized PRESS distinguished IDH-mutated glioma from non-tumor tissue with lower sensitivity (range 0.76-0.62) and specificity (0.85-0.78) than literature suggests for IDH-mutated vs. IDH-wildtype glioma. Strong negative correlations between gamma-aminobutyric acid (GABA) and 2HG persisted across all modeling strategies and may lead to false-positive 2HG detection in non-tumor tissue. We further present a cautionary example from a patient on a ketogenic diet, showing that the ketone body acetone can interfere with 2HG detection.
Spectral overlap with GABA and acetone can lead to false-positive 2HG detection in non-tumor tissue. Clinicians need to be mindful of these pitfalls when interpreting 2HG estimates.
2-羟基戊二酸（2HG）的体内磁共振波谱（MRS）可为异柠檬酸脱氢酶（IDH）突变型胶质瘤提供诊断和监测生物标志物。先前的一项荟萃分析显示，TE优化的点分辨表面线圈（PRESS）序列对IDH突变型胶质瘤具有良好的诊断准确性，但大多数研究以IDH野生型胶质瘤作为对照。然而，当考虑可能模仿胶质瘤的新发现脑病变时，对其诊断效用的全面表征还应考虑非肿瘤组织中2HG测量的准确性。因此，我们测试了TE优化的2HG水平在区分IDH突变型胶质瘤和非肿瘤组织（在本研究中为外观正常的脑）方面的效果。我们进一步研究了不同光谱建模策略（基线硬度、大分子纳入和基组组成）的影响。
纳入48例诊断/怀疑为IDH突变型胶质瘤的患者。采用PRESS定位（TE = 97 ms，针对2HG检测进行优化）从肿瘤和对侧非肿瘤组织获取3T MRS数据，并用“LCModel”软件进行分析。通过受试者操作特征分析评估2HG估计值区分IDH突变型胶质瘤与非肿瘤脑组织的能力。评估2HG与其他代谢物之间的建模相互作用，以确定2HG检测出现潜在假阳性的原因。
与文献报道的IDH突变型与IDH野生型胶质瘤相比，TE优化的PRESS序列区分IDH突变型胶质瘤与非肿瘤组织的敏感性（范围为0.76 - 0.62）和特异性（0.85 - 0.78）较低。在所有建模策略中，γ-氨基丁酸（GABA）与2HG之间均存在强负相关，这可能导致非肿瘤组织中2HG检测出现假阳性。我们还给出了一位采用生酮饮食患者的警示案例，表明酮体丙酮可干扰2HG检测。
与GABA和丙酮的光谱重叠可导致非肿瘤组织中2HG检测出现假阳性。临床医生在解释2HG估计值时需注意这些陷阱。
