Adalberto Claudio Quiros

Adalberto Claudio Quiros, Nicolas Coudray, Anna Yeaton et al.

Definitive cancer diagnosis and management depend upon the extraction of information from microscopy images by pathologists. These images contain complex information requiring time-consuming expert human interpretation that is prone to human bias. Supervised deep learning approaches have proven powerful for classification tasks, but they are inherently limited by the cost and quality of annotations used for training these models. To address this limitation of supervised methods, we developed Histomorphological Phenotype Learning (HPL), a fully blue{self-}supervised methodology that requires no expert labels or annotations and operates via the automatic discovery of discriminatory image features in small image tiles. Tiles are grouped into morphologically similar clusters which constitute a library of histomorphological phenotypes, revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer tissues, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. We then demonstrate that these properties are maintained in a multi-cancer study. These results show the clusters represent recurrent host responses and modes of tumor growth emerging under natural selection. Code, pre-trained models, learned embeddings, and documentation are available to the community at https://github.com/AdalbertoCq/Histomorphological-Phenotype-Learning

Adalberto Claudio Quiros, Nicolas Coudray, Anna Yeaton et al.

Deep learning based analysis of histopathology images shows promise in advancing the understanding of tumor progression, tumor micro-environment, and their underpinning biological processes. So far, these approaches have focused on extracting information associated with annotations. In this work, we ask how much information can be learned from the tissue architecture itself. We present an adversarial learning model to extract feature representations of cancer tissue, without the need for manual annotations. We show that these representations are able to identify a variety of morphological characteristics across three cancer types: Breast, colon, and lung. This is supported by 1) the separation of morphologic characteristics in the latent space; 2) the ability to classify tissue type with logistic regression using latent representations, with an AUC of 0.97 and 85% accuracy, comparable to supervised deep models; 3) the ability to predict the presence of tumor in Whole Slide Images (WSIs) using multiple instance learning (MIL), achieving an AUC of 0.98 and 94% accuracy. Our results show that our model captures distinct phenotypic characteristics of real tissue samples, paving the way for further understanding of tumor progression and tumor micro-environment, and ultimately refining histopathological classification for diagnosis and treatment. The code and pretrained models are available at: https://github.com/AdalbertoCq/Adversarial-learning-of-cancer-tissue-representations

Adalberto Claudio Quiros, Roderick Murray-Smith, Ke Yuan

Histopathological images of tumors contain abundant information about how tumors grow and how they interact with their micro-environment. Better understanding of tissue phenotypes in these images could reveal novel determinants of pathological processes underlying cancer, and in turn improve diagnosis and treatment options. Advances of Deep learning makes it ideal to achieve those goals, however, its application is limited by the cost of high quality labels from patients data. Unsupervised learning, in particular, deep generative models with representation learning properties provides an alternative path to further understand cancer tissue phenotypes, capturing tissue morphologies. In this paper, we develop a framework which allows GANs to capture key tissue features and uses these characteristics to give structure to its latent space. To this end, we trained our model on two different datasets, an H&E colorectal cancer tissue from the National Center for Tumor diseases (NCT) and an H&E breast cancer tissue from the Netherlands Cancer Institute (NKI) and Vancouver General Hospital (VGH). Composed of 86 slide images and 576 TMAs respectively. We show that our model generates high quality images, with a FID of 16.65 (breast cancer) and 32.05 (colorectal cancer). We further assess the quality of the images with cancer tissue characteristics (e.g. count of cancer, lymphocytes, or stromal cells), using quantitative information to calculate the FID and showing consistent performance of 9.86. Additionally, the latent space of our model shows an interpretable structure and allows semantic vector operations that translate into tissue feature transformations. Furthermore, ratings from two expert pathologists found no significant difference between our generated tissue images from real ones. The code, images, and pretrained models are available at https://github.com/AdalbertoCq/Pathology-GAN

Adalberto Claudio Quiros, Roderick Murray-Smith, Ke Yuan

Application of deep learning in digital pathology shows promise on improving disease diagnosis and understanding. We present a deep generative model that learns to simulate high-fidelity cancer tissue images while mapping the real images onto an interpretable low dimensional latent space. The key to the model is an encoder trained by a previously developed generative adversarial network, PathologyGAN. We study the latent space using 249K images from two breast cancer cohorts. We find that the latent space encodes morphological characteristics of tissues (e.g. patterns of cancer, lymphocytes, and stromal cells). In addition, the latent space reveals distinctly enriched clusters of tissue architectures in the high-risk patient group.