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体内人类脑胶质瘤分子特征分析:使用动态磁敏感对比磁共振灌注成像的横断面观察性研究。

In Vivo Molecular Profiling of Human Glioma : Cross-Sectional Observational Study Using Dynamic Susceptibility Contrast Magnetic Resonance Perfusion Imaging.

机构信息

Department of Neuroradiology, Eberhard Karls University, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Institute of Neuropathology, Eberhard Karls University, Tübingen, Germany.

出版信息

Clin Neuroradiol. 2019 Sep;29(3):479-491. doi: 10.1007/s00062-018-0676-2. Epub 2018 Feb 21.

DOI:10.1007/s00062-018-0676-2
PMID:29468261
Abstract

PURPOSE

To assess the diagnostic performance of dynamic susceptibility contrast perfusion magnetic resonance perfusion imaging (DSC-MRI) for in vivo human glioma molecular profiling.

METHODS

In this study 100 patients with histopathologically confirmed glioma who provided written informed consent were retrospectively assessed between January 2016 and February 2017 in two prospective trials that were approved by the local institutional review board. Cerebral blood volume (CBV) measurements from DSC-MRI were assessed, and histogram parameters of relative CBV (rCBV) results were compared among World Health Organization (WHO) 2016 based histological findings and molecular characteristics. A classification and regression tree (CART) algorithm with 10-fold cross-validation was used to calculate the diagnostic accuracy.

RESULTS

The 90th percentile (C90) of rCBV was significantly lower in patients with the isocitrate dehydrogenase 1/2 (IDH1/2) mutation (2.86 ± 1.21; p < 0.001) and loss of alpha-thalassemia mental retardation syndrome X‑linked (ATRX) expression (2.23 ± 0.91; p < 0.001) than in those with the IDH1/2 wild type (4.78 ± 2.34) and maintained ATRX expression (4.30 ± 2.02). The standard deviation (SD) of rCBV was significantly higher in glioblastoma (GBM) with methylated O6-methylguanine DNA methyltransferase (MGMT; 1.99 ± 0.73; p = 0.001) than in those with unmethylated MGMT (1.20 ± 0.45). In CART analysis, rCBV predicted the molecular subgroup in 76.3% of astroglial tumors; however, the diagnostic performance was reduced to 48.1% by including oligodendrogliomas with chromosome 1p/19q co-deletion in the analysis due to substantial overlap of rCBV values between OD and IDH GBM.

CONCLUSION

The DSC-MRI procedure may provide insight into the IDH1/2 mutation and ATRX expression status and MGMT methylation profile of diffuse glioma; however, taking integrated oligodendroglioma into account limits the diagnostic performance of rCBV in non-invasively predicting the molecular subtype.

摘要

目的

评估动态磁敏感对比灌注磁共振灌注成像(DSC-MRI)在人胶质瘤分子谱分析中的诊断性能。

方法

本研究回顾性评估了 2016 年 1 月至 2017 年 2 月期间在两项经当地机构审查委员会批准的前瞻性试验中提供书面知情同意的 100 名经组织病理学证实的胶质瘤患者。评估 DSC-MRI 的脑血容量(CBV)测量值,并比较基于 2016 年世界卫生组织(WHO)的组织学发现和分子特征的相对 CBV(rCBV)结果的直方图参数。使用 10 倍交叉验证的分类回归树(CART)算法计算诊断准确性。

结果

IDH1/2 突变(2.86±1.21;p<0.001)和 ATRX 表达缺失(2.23±0.91;p<0.001)患者的 rCBV 第 90 百分位数(C90)明显低于 IDH1/2 野生型(4.78±2.34)和 ATRX 表达保持者(4.30±2.02)。胶质母细胞瘤(GBM)中 rCBV 的标准差(SD)明显高于甲基化 O6-甲基鸟嘌呤 DNA 甲基转移酶(MGMT;1.99±0.73;p=0.001),低于未甲基化 MGMT(1.20±0.45)。在 CART 分析中,rCBV 预测了 76.3%的星形细胞瘤的分子亚群;然而,由于 IDH 型 GBM 和 ODG 之间 rCBV 值存在大量重叠,当将染色体 1p/19q 共缺失的少突胶质细胞瘤纳入分析时,诊断性能降低至 48.1%。

结论

DSC-MRI 检查程序可提供关于弥漫性胶质瘤 IDH1/2 突变和 ATRX 表达状态以及 MGMT 甲基化谱的信息;然而,考虑到整合性少突胶质细胞瘤,rCBV 在非侵入性预测分子亚型方面的诊断性能受到限制。

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