Han Lichy, Kamdar Maulik R
Program in Biomedical Informatics, Stanford University, Stanford, CA 94305, USA,
Pac Symp Biocomput. 2018;23:331-342.
Glioblastoma Multiforme (GBM), a malignant brain tumor, is among the most lethal of all cancers. Temozolomide is the primary chemotherapy treatment for patients diagnosed with GBM. The methylation status of the promoter or the enhancer regions of the O6-methylguanine methyltransferase (MGMT) gene may impact the efficacy and sensitivity of temozolomide, and hence may affect overall patient survival. Microscopic genetic changes may manifest as macroscopic morphological changes in the brain tumors that can be detected using magnetic resonance imaging (MRI), which can serve as noninvasive biomarkers for determining methylation of MGMT regulatory regions. In this research, we use a compendium of brain MRI scans of GBM patients collected from The Cancer Imaging Archive (TCIA) combined with methylation data from The Cancer Genome Atlas (TCGA) to predict the methylation state of the MGMT regulatory regions in these patients. Our approach relies on a bi-directional convolutional recurrent neural network architecture (CRNN) that leverages the spatial aspects of these 3-dimensional MRI scans. Our CRNN obtains an accuracy of 67% on the validation data and 62% on the test data, with precision and recall both at 67%, suggesting the existence of MRI features that may complement existing markers for GBM patient stratification and prognosis. We have additionally presented our model via a novel neural network visualization platform, which we have developed to improve interpretability of deep learning MRI-based classification models.
多形性胶质母细胞瘤(GBM)是一种恶性脑肿瘤,是所有癌症中致死率最高的癌症之一。替莫唑胺是诊断为GBM患者的主要化疗药物。O6-甲基鸟嘌呤甲基转移酶(MGMT)基因启动子或增强子区域的甲基化状态可能会影响替莫唑胺的疗效和敏感性,进而可能影响患者的总体生存期。微观基因变化可能表现为脑肿瘤的宏观形态变化,可通过磁共振成像(MRI)检测到,MRI可作为确定MGMT调控区域甲基化的非侵入性生物标志物。在本研究中,我们使用从癌症影像存档(TCIA)收集的GBM患者脑部MRI扫描数据集,并结合来自癌症基因组图谱(TCGA)的甲基化数据,来预测这些患者中MGMT调控区域的甲基化状态。我们的方法依赖于双向卷积循环神经网络架构(CRNN),该架构利用了这些三维MRI扫描的空间特征。我们的CRNN在验证数据上的准确率为67%,在测试数据上的准确率为62%,精确率和召回率均为67%,这表明存在一些MRI特征,可能补充用于GBM患者分层和预后的现有标志物。我们还通过一个新颖的神经网络可视化平台展示了我们的模型,该平台是我们为提高基于MRI的深度学习分类模型的可解释性而开发的。