作为代谢失调间接标志物的肿瘤空间特征：利用混合[18F]FET-PET/MRI对胶质瘤进行无创异柠檬酸脱氢酶（IDH）基因分型的评估
Spatial tumour characteristics as an indirect marker of metabolic dysregulation: evaluation for non-invasive IDH-genotyping of glioma using hybrid [18 F]FET-PET/MRI.
作者信息
Lohmeier Johannes, Meinhardt Jenny, Radbruch Helena, Reyes Mauricio, Brenner Winfried, Tietze Anna, Makowski Marcus R
机构信息
Institute of Neuroradiology, Campus Charité Mitte (CCM), Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Department of Neuropathology, Campus Charité Mitte (CCM, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, Berlin, 10117, Germany.
出版信息
Eur J Nucl Med Mol Imaging. 2025 Aug 28. doi: 10.1007/s00259-025-07520-8.
PURPOSE
The isocitrate dehydrogenase (IDH) genotype is crucial for diagnosing and managing adult-type diffuse glioma. We investigated spatial tumour characteristics in treatment-naïve glioma using an U-Net-based CNN and evaluated associations with metabolic dysfunction and IDH genotype.
METHODS
Between 2015 and 2024 patients with confirmed contrast-enhancing glioma were pre-operatively investigated using MRI or [18 F]FET PET/MRI. Automated morphometry using a U-Net-based CNN on standard MRI sequences (T1c, T1, T2, FLAIR) was performed. Contrast-enhancing tumour fraction (CTF), metabolic tumour volume (MTV), total tumour volume (TTV) were determined. Dice coefficient assessed volume intersections. Comparative and statistical analyses included non-parametric tests, ROC curves, regression, and correlation.
RESULTS
A total of 180 patients (male, 114; female, 66; age, M ± SD = 54 ± 15y; IDH-mutant, 63; IDH wild-type, 117) with treatment-naïve glioma were evaluated. [18 F]FET-PET metabolic activity correlated significantly with CTF (p < .05). IDH-mutant gliomas had lower CTF (p < .001) due to higher non-enhancing tumour mass (p < .001) relative to the enhancing mass, unlike IDH wild-type glioblastoma. The CTF predicted IDH genotype with high accuracy (AUC = 0.85, sensitivity 78%, specificity 90%) across datasets. Combining CTF with patient age or SUVmax further improved the classification (ΔAUC = 0.12, p = .02; ΔAUC = 0.09, p > .05). Subgroup analyses showed consistent performance across IDH-mutant subtypes. MTV from [18 F]FET-PET exceeded structurally apparent TTV (p = .033).
CONCLUSION
Spatial mapping of treatment-naïve glioma identified a non-invasive biomarker, which is linked to metabolic dysfunction and enabled robust IDH-genotype classification from standard MRI, suggesting a central role for radiogenomic assessment in adult-type diffuse gliomas prior to surgery.
目的
异柠檬酸脱氢酶（IDH）基因型对于诊断和管理成人型弥漫性胶质瘤至关重要。我们使用基于U-Net的卷积神经网络（CNN）研究了未经治疗的胶质瘤的肿瘤空间特征，并评估了其与代谢功能障碍和IDH基因型的关联。
方法
在2015年至2024年期间，对确诊为强化胶质瘤的患者在术前进行了MRI或[18F]FET PET/MRI检查。使用基于U-Net的CNN对标准MRI序列（T1c、T1、T2、FLAIR）进行自动形态测量。测定强化肿瘤分数（CTF）、代谢肿瘤体积（MTV）、总肿瘤体积（TTV）。Dice系数评估体积交集。比较和统计分析包括非参数检验、ROC曲线、回归和相关性分析。
结果
共评估了180例未经治疗的胶质瘤患者（男性114例，女性66例；年龄，M±SD = 54±15岁；IDH突变型63例，IDH野生型117例）。[18F]FET-PET代谢活性与CTF显著相关（p < 0.05）。与IDH野生型胶质母细胞瘤不同，IDH突变型胶质瘤由于相对于强化肿块更高的非强化肿瘤质量（p < 0.001）而具有较低的CTF（p < 0.001）。CTF在各数据集中对IDH基因型的预测准确率较高（AUC = 0.85，敏感性78%，特异性90%）。将CTF与患者年龄或SUVmax相结合可进一步改善分类（ΔAUC = 0.12，p = 0.02；ΔAUC = 0.09，p > 0.05）。亚组分析显示在IDH突变亚型中表现一致。[18F]FET-PET的MTV超过了结构上明显的TTV（p = 0.033）。
结论
未经治疗的胶质瘤的空间映射确定了一种非侵入性生物标志物，其与代谢功能障碍相关，并能够从标准MRI中进行可靠的IDH基因型分类，这表明放射基因组评估在成人型弥漫性胶质瘤术前具有核心作用。
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