Cancer diagnosis, prognosis, and therapy response predictions from tissue specimens highly depend on the phenotype and topological distribution of constituting histological entities. Thus, adequate tissue representations for encoding histological entities is imperative for computer aided cancer patient care. To this end, several approaches have leveraged cell-graphs, capturing the cell-microenvironment, to depict the tissue. These allow for utilizing graph theory and machine learning to map the tissue representation to tissue functionality, and quantify their relationship. Though cellular information is crucial, it is incomplete alone to comprehensively characterize complex tissue structure. We herein treat the tissue as a hierarchical composition of multiple types of histological entities from fine to coarse level, capturing multivariate tissue information at multiple levels. We propose a novel multi-level hierarchical entity-graph representation of tissue specimens to model the hierarchical compositions that encode histological entities as well as their intra- and inter-entity level interactions. Subsequently, a hierarchical graph neural network is proposed to operate on the hierarchical entity-graph and map the tissue structure to tissue functionality. Specifically, for input histology images, we utilize well-defined cells and tissue regions to build HierArchical Cell-to-Tissue (HACT) graph representations, and devise HACT-Net, a message passing graph neural network, to classify the HACT representations. As part of this work, we introduce the BReAst Carcinoma Subtyping (BRACS) dataset, a large cohort of Haematoxylin & Eosin stained breast tumor regions-of-interest, to evaluate and benchmark our proposed methodology against pathologists and state-of-the-art computer-aided diagnostic approaches. Through comparative assessment and ablation studies, our proposed method is demonstrated to yield superior classification results compared to alternative methods as well as individual pathologists. The code, data, and models can be accessed at https://github.com/histocartography/hact-net.

Explainability of deep learning methods is imperative to facilitate their clinical adoption in digital pathology. However, popular deep learning methods and explainability techniques (explainers) based on pixel-wise processing disregard biological entities’ notion, thus complicating comprehension by pathologists. In this work, we address this by adopting biological entity-based graph processing and graph explainers enabling explanations accessible to pathologists. In this context, a major challenge becomes to discern meaningful explainers, particularly in a standardized and quantifiable fashion. To this end, we propose herein a set of novel quantitative metrics based on statistics of class separability using pathologically measurable concepts to characterize graph explainers. We employ the proposed metrics to evaluate three types of graph explainers, namely the layer-wise relevance propagation, gradient-based saliency, and graph pruning approaches, to explain Cell-Graph representations for Breast Cancer Subtyping. The proposed metrics are also applicable in other domains by using domain-specific intuitive concepts. We validate the qualitative and quantitative findings on the BRACS dataset, a large cohort of breast cancer RoIs, by expert pathologists. The code, data, and models can be accessed here1.

Variations in the shape and appearance of anatomical structures in medical images are often relevant radiological signs of disease. Automatic tools can help automate parts of this manual process. A cloud-based evaluation framework is presented in this paper including results of benchmarking current state-of-the-art medical imaging algorithms for anatomical structure segmentation and landmark detection: the VISCERAL Anatomy benchmarks. The algorithms are implemented in virtual machines in the cloud where participants can only access the training data and can be run privately by the benchmark administrators to objectively compare their performance in an unseen common test set. Overall, 120 computed tomography and magnetic resonance patient volumes were manually annotated to create a standard Gold Corpus containing a total of 1295 structures and 1760 landmarks. Ten participants contributed with automatic algorithms for the organ segmentation task, and three for the landmark localization task. Different algorithms obtained the best scores in the four available imaging modalities and for subsets of anatomical structures. The annotation framework, resulting data set, evaluation setup, results and performance analysis from the three VISCERAL Anatomy benchmarks are presented in this article. Both the VISCERAL data set and Silver Corpus generated with the fusion of the participant algorithms on a larger set of non-manually-annotated medical images are available to the research community.

We propose a texture learning approach that exploits local organizations of scales and directions. First, linear combinations of Riesz wavelets are learned using kernel support vector machines. The resulting texture signatures are modeling optimal class-wise discriminatory properties. The visualization of the obtained signatures allows verifying the visual relevance of the learned concepts. Second, the local orientations of the signatures are optimized to maximize their responses, which is carried out analytically and can still be expressed as a linear combination of the initial steerable Riesz templates. The global process is iteratively repeated to obtain final rotation-covariant texture signatures. Rapid convergence of class-wise signatures is observed, which demonstrates that the instances are projected into a feature space that leverages the local organizations of scales and directions. Experimental evaluation reveals average classification accuracies in the range of 97% to 98% for the Outex_TC_00010, the Outex_TC_00012, and the Contrib_TC_00000 suites for even orders of the Riesz transform, and suggests high robustness to changes in images orientation and illumination. The proposed framework requires no arbitrary choices of scales and directions and is expected to perform well in a large range of computer vision applications.