S. D. Price

Xiaofei Wang, Stephen Price, Chao Li

Most recently, the pathology diagnosis of cancer is shifting to integrating molecular makers with histology features. It is a urgent need for digital pathology methods to effectively integrate molecular markers with histology, which could lead to more accurate diagnosis in the real world scenarios. This paper presents a first attempt to jointly predict molecular markers and histology features and model their interactions for classifying diffuse glioma bases on whole slide images. Specifically, we propose a hierarchical multi-task multi-instance learning framework to jointly predict histology and molecular markers. Moreover, we propose a co-occurrence probability-based label correction graph network to model the co-occurrence of molecular markers. Lastly, we design an inter-omic interaction strategy with the dynamical confidence constraint loss to model the interactions of histology and molecular markers. Our experiments show that our method outperforms other state-of-the-art methods in classifying diffuse glioma,as well as related histology and molecular markers on a multi-institutional dataset.

Lipei Zhang, Yiran Wei, Ying Fu et al.

Whole slide images (WSI) provide valuable phenotypic information for histological assessment and malignancy grading of tumors. The WSI-based grading promises to provide rapid diagnostic support and facilitate digital health. Currently, the most commonly used WSIs are derived from formalin-fixed paraffin-embedded (FFPE) and Frozen section. The majority of automatic tumor grading models are developed based on FFPE sections, which could be affected by the artifacts introduced by tissue processing. The frozen section exists problems such as low quality that might influence training within single modality as well. To overcome this problem in a single modal training and achieve better multi-modal and discriminative representation disentanglement in brain tumor, we propose a mutual contrastive low-rank learning (MCL) scheme to integrate FFPE and frozen sections for glioma grading. We first design a mutual learning scheme to jointly optimize the model training based on FFPE and frozen sections. In this proposed scheme, we design a normalized modality contrastive loss (NMC-loss), which could promote to disentangle multi-modality complementary representation of FFPE and frozen sections from the same patient. To reduce intra-class variance, and increase inter-class margin at intra- and inter-patient levels, we conduct a low-rank (LR) loss. Our experiments show that the proposed scheme achieves better performance than the model trained based on each single modality or mixed modalities and even improves the feature extraction in classical attention-based multiple instances learning methods (MIL). The combination of NMC-loss and low-rank loss outperforms other typical contrastive loss functions.

Xiaofei Wang, Hanyu Liu, Yupei Zhang et al.

Cancers are characterized by remarkable heterogeneity and diverse prognosis. Accurate cancer classification is essential for patient stratification and clinical decision-making. Although digital pathology has been advancing cancer diagnosis and prognosis, the paradigm in cancer pathology has shifted from purely relying on histology features to incorporating molecular markers. There is an urgent need for digital pathology methods to meet the needs of the new paradigm. We introduce a novel digital pathology approach to jointly predict molecular markers and histology features and model their interactions for cancer classification. Firstly, to mitigate the challenge of cross-magnification information propagation, we propose a multi-scale disentangling module, enabling the extraction of multi-scale features from high-magnification (cellular-level) to low-magnification (tissue-level) whole slide images. Further, based on the multi-scale features, we propose an attention-based hierarchical multi-task multi-instance learning framework to simultaneously predict histology and molecular markers. Moreover, we propose a co-occurrence probability-based label correlation graph network to model the co-occurrence of molecular markers. Lastly, we design a cross-modal interaction module with the dynamic confidence constrain loss and a cross-modal gradient modulation strategy, to model the interactions of histology and molecular markers. Our experiments demonstrate that our method outperforms other state-of-the-art methods in classifying glioma, histology features and molecular markers. Our method promises to promote precise oncology with the potential to advance biomedical research and clinical applications. The code is available at https://github.com/LHY1007/M3C2

Yifan Li, Chao Li, Yiran Wei et al.

Glioblastoma is profoundly heterogeneous in regional microstructure and vasculature. Characterizing the spatial heterogeneity of glioblastoma could lead to more precise treatment. With unsupervised learning techniques, glioblastoma MRI-derived radiomic features have been widely utilized for tumor sub-region segmentation and survival prediction. However, the reliability of algorithm outcomes is often challenged by both ambiguous intermediate process and instability introduced by the randomness of clustering algorithms, especially for data from heterogeneous patients. In this paper, we propose an adaptive unsupervised learning approach for efficient MRI intra-tumor partitioning and glioblastoma survival prediction. A novel and problem-specific Feature-enhanced Auto-Encoder (FAE) is developed to enhance the representation of pairwise clinical modalities and therefore improve clustering stability of unsupervised learning algorithms such as K-means. Moreover, the entire process is modelled by the Bayesian optimization (BO) technique with a custom loss function that the hyper-parameters can be adaptively optimized in a reasonably few steps. The results demonstrate that the proposed approach can produce robust and clinically relevant MRI sub-regions and statistically significant survival predictions.