Borges de Almeida Gonçalo, Pascuzzo Riccardo, Mambrin Francesca, Aquino Domenico, Verri Mattia, Moscatelli Marco, Del Bene Massimiliano, DiMeco Francesco, Silvani Antonio, Pollo Bianca, Grisoli Marina, Doniselli Fabio Martino
Department of Neuroradiology, Hospital de São José, 1150-199 Lisbon, Portugal.
Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy.
Cancers (Basel). 2024 Aug 29;16(17):3014. doi: 10.3390/cancers16173014.
Amide Proton Transfer-weighted (APTw) imaging is a molecular MRI technique used to quantify protein concentrations in gliomas, which have heterogeneous components with varying cellularity and metabolic activity. This study aimed to assess the correlation between the component-specific APT signal of the neoplasm and WHO grade, molecular profile and survival status. Sixty-one patients with adult-type diffuse gliomas were retrospectively analyzed. APT values were semi-automatically extracted from tumor solid and, whenever present, necrotic components. APT values were compared between groups stratified by WHO grade, IDH-mutation, MGMT promoter methylation and 1- and 2-year survival status using Wilcoxon rank-sum test, adjusting for multiple comparisons. Overall survival (OS) was analyzed in the subgroup of 48 patients with grade 4 tumors using Cox proportional-hazards models. Random-effects models were used to assess inter-subject heterogeneity of the mean APT values in each tumor component. APT values of the solid component significantly differed between patients with grades 2-3 and 4 tumors (mean 1.58 ± 0.50 vs. 2.04 ± 0.56, = 0.028) and correlated with OS after 1 year (1.81 ± 0.58 in survivors vs. 2.17 ± 0.51 in deceased patients, = 0.030). APT values did not differ by IDH-mutation, MGMT methylation, and 2-year survival status. Within grade 4 glioma patients, higher APT kurtosis of the solid component was a negative prognostic factor (hazard ratio = 1.60, = 0.040). Mean APT values of the necrosis showed high inter-subject variability, although most necrotic tumors were grade 4 and IDH wildtype. In conclusion, APTw imaging in the solid component provided metrics associated with glioma grade and survival status but showed weak correlation with IDH-mutation and MGMT promoter methylation status, in contrast to previous works. Further research is needed to understand APT signal variability within the necrotic component of high-grade gliomas.
酰胺质子转移加权（APTw）成像技术是一种分子磁共振成像技术，用于量化胶质瘤中的蛋白质浓度，胶质瘤具有异质性成分，其细胞密度和代谢活性各不相同。本研究旨在评估肿瘤成分特异性APT信号与世界卫生组织（WHO）分级、分子特征和生存状态之间的相关性。对61例成人型弥漫性胶质瘤患者进行回顾性分析。APT值从肿瘤实性成分中半自动提取，如有坏死成分也一并提取。使用Wilcoxon秩和检验比较按WHO分级、异柠檬酸脱氢酶（IDH）突变、O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化以及1年和2年生存状态分层的组间APT值，并对多重比较进行校正。使用Cox比例风险模型分析48例4级肿瘤患者亚组的总生存期（OS）。采用随机效应模型评估各肿瘤成分中平均APT值的受试者间异质性。2-3级和4级肿瘤患者的实性成分APT值存在显著差异（平均值分别为1.58±0.50和2.04±0.56，P=0.028），且与1年后的OS相关（存活患者为1.81±0.58，死亡患者为2.17±0.51，P=0.030）。APT值在IDH突变、MGMT甲基化和2年生存状态方面无差异。在4级胶质瘤患者中，实性成分较高的APT峰度是一个负性预后因素（风险比=1.60，P=0.040）。坏死成分的平均APT值显示出较高的受试者间变异性，尽管大多数坏死性肿瘤为4级且IDH野生型。总之，与以往研究不同，实性成分的APTw成像提供了与胶质瘤分级和生存状态相关的指标，但与IDH突变和MGMT启动子甲基化状态的相关性较弱。需要进一步研究以了解高级别胶质瘤坏死成分内的APT信号变异性。
