Durmo Faris, Lätt Jimmy, Rydelius Anna, Englund Elisabet, Salomonsson Tim, Liebig Patrick, Bengzon Johan, van Zijl Peter C M, Knutsson Linda, Sundgren Pia C
Department of Clinical Sciences/Division of Radiology, Lund University, SE-221 00 Lund, Sweden.
Department of Medical Imaging and Physiology, Skåne University Hospital, SE-221 85 Lund, Sweden.
Tomography. 2025 May 31;11(6):64. doi: 10.3390/tomography11060064.
To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid. A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression. The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG, = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%, = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%, = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal. : APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making.
评估酰胺质子转移加权（APTw）磁共振成像（MRI）在区分不同α-地中海贫血/智力发育迟缓X连锁（ATRX）表达、肿瘤抑制蛋白p53表达（p53）、O6-甲基鸟嘌呤-DNA甲基转移酶启动子（MGMTp）甲基化、异柠檬酸脱氢酶（IDH）状态以及增殖标志物Ki-67（Ki-67指数）的高级别胶质瘤方面的能力，作为术前诊断辅助手段。前瞻性评估了总共42例世界卫生组织4级高级别胶质瘤（HGG）患者（30例男性和12例女性）。所有患者均使用传统MRI进行检查，包括以下内容：T1w-MPRAGE对比剂注射前后、传统T2w和3D FLAIR，以及使用3T MR扫描仪进行APTw成像。针对不同分子生物标志物的APTw%均值、中位数和最大信号计算了受试者操作特征（ROC）曲线。构建了一个逻辑回归模型，用于p53表达的APTw%均值和中位数信号的组合。全肿瘤最大APTw%信号能够显著区分MGMTp甲基化与非MGMTp甲基化的HGG，P = 0.035。最大APTw%信号截断值为4.28%时，曲线下面积（AUC）= 0.702，敏感性为70.6%，特异性为66.7%。p53正常与p53过表达的HGG中，APTw%均值/中位数信号存在显著差异：分别为1.81%/1.83%与1.15%/1.18%，P分别为0.002/0.006。APTw%均值/中位数信号截断值为1.25%/1.33%时，AUC分别为0.786/0.757，敏感性为76.9%/76.9%，特异性为50%/66.2%，P分别为0.002/0.006。一个用于p53状态的APTw%均值和中位数信号组合的逻辑回归模型，AUC = 0.788，敏感性为76.9%，特异性为66.2%。ATRX、IDH野生型（wt）与突变型（mut）以及Ki-67水平无显著差异，但发现了一些趋势：IDH-wt和低Ki-67分别显示出比IDH-mut和高Ki-67更高的APTw%均值/中位数/最大信号。ATRX-wt与突变型相比，显示出更高的APTw%均值和中位数信号，但最大APTw%信号更低。结论：APTw成像可能是术前高级别胶质瘤中p53表达和MGMT状态分层的有用标志物，并可能有助于手术决策。
