IEEE Trans Med Imaging. 2018 Aug;37(8):1775-1787. doi: 10.1109/TMI.2018.2807590. Epub 2018 Feb 19.
The O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase 1 (IDH1) mutation in high-grade gliomas (HGG) have proven to be the two important molecular indicators associated with better prognosis. Traditionally, the statuses of MGMT and IDH1 are obtained via surgical biopsy, which has limited their wider clinical implementation. Accurate presurgical prediction of their statuses based on preoperative multimodal neuroimaging is of great clinical value for a better treatment plan. Currently, the available data set associated with this study has several challenges, such as small sample size and complex, nonlinear (image) feature-to-(molecular) label relationship. To address these issues, we propose a novel multi-label nonlinear matrix completion (MNMC) model to jointly predict both MGMT and IDH1 statuses in a multi-task framework. Specifically, we first employ a nonlinear random Fourier feature mapping to improve the linear separability of the data, and then use transductive multi-task feature selection (performed in a nonlinearly transformed feature space) to refine the imputed soft labels, thus alleviating the overfitting problem caused by small sample size. We further design an optimization algorithm with a guaranteed convergence ability based on a block prox-linear method to solve the proposed MNMC model. Finally, by using a single-center, multimodal brain imaging and molecular pathology data set of HGG, we derive brain functional and structural connectomics features to jointly predict MGMT and IDH1 statuses. Results demonstrate that our proposed method outperforms the previously widely used single- and multi-task machine learning methods. This paper also shows the promise of utilizing brain connectomics for HGG prognosis in a non-invasive manner.
O6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)启动子甲基化和异柠檬酸脱氢酶 1(IDH1)突变已被证明是与更好的预后相关的两个重要分子指标。传统上,MGMT 和 IDH1 的状态是通过手术活检获得的,这限制了它们更广泛的临床应用。基于术前多模态神经影像学准确预测它们的状态对制定更好的治疗计划具有重要的临床价值。目前,与这项研究相关的可用数据集存在几个挑战,例如样本量小和复杂的非线性(图像)特征到(分子)标签关系。为了解决这些问题,我们提出了一种新的多标签非线性矩阵补全(MNMC)模型,以在多任务框架中联合预测 MGMT 和 IDH1 状态。具体来说,我们首先采用非线性随机傅里叶特征映射来提高数据的线性可分离性,然后使用传递性多任务特征选择(在非线性变换的特征空间中执行)来细化推断的软标签,从而减轻由于样本量小而导致的过拟合问题。我们进一步设计了一种基于块逐线性方法的具有保证收敛能力的优化算法来解决所提出的 MNMC 模型。最后,通过使用 HGG 的单中心、多模态脑成像和分子病理学数据集,我们推导出脑功能和结构连接组学特征,以联合预测 MGMT 和 IDH1 状态。结果表明,我们提出的方法优于以前广泛使用的单任务和多任务机器学习方法。本文还展示了利用脑连接组学无创地预测 HGG 预后的潜力。