A weakly supervised NMF method to decipher molecular subtype-related dynamic patterns in breast DCE-MR images

Abstract

Objective. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an important imaging modality for breast cancer diagnosis. Intratumoral heterogeneity causes a major challenge in the interpretation of breast DCE-MRI. Previous studies have introduced decomposition methods on DCE-MRI to reveal intratumoral heterogeneity by analyzing distinct dynamic patterns within each tumor. However, these methods estimated the dynamic patterns and their corresponding component coefficients in an unsupervised manner, without considering any clinically relevant information. Approach. To decipher molecular subtype-related dynamic patterns, we propose a weakly supervised nonnegative matrix factorization method (WSNMF), which is able to decompose the pixel kinetics of DCE-MRI with image-level subtype labels. The WSNMF is developed based on a discriminant NMF to utilize coarse-grained subtype information, in which between- and within-class scatters are defined on the mean vector of component coefficients over all pixels in each tumor, rather than directly on the vector of component coefficients of each pixel. Main results. Experiments demonstrated that the dynamic patterns identified by WSNMF had superior performance in distinguishing between luminal A and the other subtype tumors. The classification performance was evaluated using the area under the receiver operating characteristic curve (AUC). WSNMF yielded better classification performance (AUC = 0.822) than other heterogeneity analysis methods, including two partitioning based methods (KPC with AUC = 0.697 and TTP with AUC =0.760) and two unsupervised decomposition-based methods (PCA with AUC = 0.774 and NMF with AUC = 0.797). Significance. Our method adds a valuable new perspective into DCEMRI decomposition-based heterogeneity analysis by taking advantage of intrinsic tumor characteristics to improve the diagnosis of breast cancer.