Update on the current opinion, status and future development of digital pathology in Switzerland in light of COVID-19.

The transition from analogue to digital pathology (DP) in Switzerland has coincided with the COVID-19 crisis. The Swiss Digital Pathology Consortium conducted a national survey to assess the experience of pathologists in dealing with the challenges of the pandemic and how this has influenced the outlook and adoption of DP. A survey containing 20 questions relating to DP, personal experiences and challenges during the pandemic was addressed to Swiss pathologists at different experience stages in private practice, community and university hospitals. All 74 respondents were pathologists, with 81.1% reporting more than 5 years of diagnostic service experience. 32.5% reported having read 100 digital slides or more in a diagnostic context. 39.2% reported using whole slide imaging systems at their primary workplace. Key DP use cases before the COVID-19 lockdown were tumour boards (39.2%), education (60.8%) and research (44.6%), with DP used for primary diagnosis in 13.5%. During the COVID-19 crisis, the use of DP for primary diagnostics more than doubled (30% vs 13.5%), with internal consults as important drivers (22.5% vs 16.5%), while research use (25% vs 44.6%) and external consults (17.5% vs 41.9%) strongly decreased. Key challenges identified included a lack of established standard operating procedures and availability of specialised hardware and software. This survey indicates that the crisis acted as a catalyst in promoting DP adoption in centres where basic workflows were already established while posing major technical and organisational challenges in institutions that were at an early stage of DP implementation

Quick Annotator: an open-source digital pathology based rapid image annotation tool.

Image-based biomarker discovery typically requires accurate segmentation of histologic structures (e.g. cell nuclei, tubules, and epithelial regions) in digital pathology whole slide images (WSIs). Unfortunately, annotating each structure of interest is laborious and often intractable even in moderately sized cohorts. Here, we present an open-source tool, Quick Annotator (QA), designed to improve annotation efficiency of histologic structures by orders of magnitude. While the user annotates regions of interest (ROIs) via an intuitive web interface, a deep learning (DL) model is concurrently optimized using these annotations and applied to the ROI. The user iteratively reviews DL results to either (1) accept accurately annotated regions or (2) correct erroneously segmented structures to improve subsequent model suggestions, before transitioning to other ROIs. We demonstrate the effectiveness of QA over comparable manual efforts via three use cases. These include annotating (1) 337,386 nuclei in 5 pancreatic WSIs, (2) 5,692 tubules in 10 colorectal WSIs, and (3) 14,187 regions of epithelium in 10 breast WSIs. Efficiency gains in terms of annotations per second of 102×, 9×, and 39× were, respectively, witnessed while retaining f-scores >0.95, suggesting that QA may be a valuable tool for efficiently fully annotating WSIs employed in downstream biomarker studies

Structure Preserving Stain Normalization of Histopathology Images Using Self Supervised Semantic Guidance

© 2020, Springer Nature Switzerland AG. Although generative adversarial network (GAN) based style transfer is state of the art in histopathology color-stain normalization, they do not explicitly integrate structural information of tissues. We propose a self-supervised approach to incorporate semantic guidance into a GAN based stain normalization framework and preserve detailed structural information. Our method does not require manual segmentation maps which is a significant advantage over existing methods. We integrate semantic information at different layers between a pre-trained semantic network and the stain color normalization network. The proposed scheme outperforms other color normalization methods leading to better classification and segmentation performance

A prognostic model for overall survival of patients with early-stage non-small cell lung cancer: a multicentre, retrospective study.

Intratumoural heterogeneity has been previously shown to be related to clonal evolution and genetic instability and associated with tumour progression. Phenotypically, it is reflected in the diversity of appearance and morphology within cell populations. Computer-extracted features relating to tumour cellular diversity on routine tissue images might correlate with outcome. This study investigated the prognostic ability of computer-extracted features of tumour cellular diversity (CellDiv) from haematoxylin and eosin (H&E)-stained histology images of non-small cell lung carcinomas (NSCLCs). In this multicentre, retrospective study, we included 1057 patients with early-stage NSCLC with corresponding diagnostic histology slides and overall survival information from four different centres. CellDiv features quantifying local cellular morphological diversity from H&E-stained histology images were extracted from the tumour epithelium region. A Cox proportional hazards model based on CellDiv was used to construct risk scores for lung adenocarcinoma (LUAD; 270 patients) and lung squamous cell carcinoma (LUSC; 216 patients) separately using data from two of the cohorts, and was validated in the two remaining independent cohorts (comprising 236 patients with LUAD and 335 patients with LUSC). We used multivariable Cox regression analysis to examine the predictive ability of CellDiv features for 5-year overall survival, controlling for the effects of clinical and pathological parameters. We did a gene set enrichment and Gene Ontology analysis on 405 patients to identify associations with differentially expressed biological pathways implicated in lung cancer pathogenesis. For prognosis of patients with early-stage LUSC, the CellDiv LUSC model included 11 discriminative CellDiv features, whereas for patients with early-stage LUAD, the model included 23 features. In the independent validation cohorts, patients predicted to be at a higher risk by the univariable CellDiv model had significantly worse 5-year overall survival (hazard ratio 1·48 [95% CI 1·06-2·08]; p=0·022 for The Cancer Genome Atlas [TCGA] LUSC group, 2·24 [1·04-4·80]; p=0·039 for the University of Bern LUSC group, and 1·62 [1·15-2·30]; p=0·0058 for the TCGA LUAD group). The identified CellDiv features were also found to be strongly associated with apoptotic signalling and cell differentiation pathways. CellDiv features were strongly prognostic of 5-year overall survival in patients with early-stage NSCLC and also associated with apoptotic signalling and cell differentiation pathways. The CellDiv-based risk stratification model could potentially help to determine which patients with early-stage NSCLC might receive added benefit from adjuvant therapy. National Institue of Health and US Department of Defense

TriResNet: A Deep Triple-stream Residual Network for Histopathology Grading

While microscopic analysis of histopathological slides is generally considered as the gold standard method for performing cancer diagnosis and grading, the current method for analysis is extremely time consuming and labour intensive as it requires pathologists to visually inspect tissue samples in a detailed fashion for the presence of cancer. As such, there has been significant recent interest in computer aided diagnosis systems for analysing histopathological slides for cancer grading to aid pathologists to perform cancer diagnosis and grading in a more efficient, accurate, and consistent manner. In this work, we investigate and explore a deep triple-stream residual network (TriResNet) architecture for the purpose of tile-level histopathology grading, which is the critical first step to computer-aided whole-slide histopathology grading. In particular, the design mentality behind the proposed TriResNet network architecture is to facilitate for the learning of a more diverse set of quantitative features to better characterize the complex tissue characteristics found in histopathology samples. Experimental results on two widely-used computer-aided histopathology benchmark datasets (CAMELYON16 dataset and Invasive Ductal Carcinoma (IDC) dataset) demonstrated that the proposed TriResNet network architecture was able to achieve noticeably improved accuracies when compared with two other state-of-the-art deep convolutional neural network architectures. Based on these promising results, the hope is that the proposed TriResNet network architecture could become a useful tool to aiding pathologists increase the consistency, speed, and accuracy of the histopathology grading process.Comment: 9 page

Bringing Open Data to Whole Slide Imaging

Supplementary information associated with Besson et al. (2019) ECDP 2019 Faced with the need to support a growing number of whole slide imaging (WSI) file formats, our team has extended a long-standing community file format (OME-TIFF) for use in digital pathology. The format makes use of the core TIFF specification to store multi-resolution (or "pyramidal") representations of a single slide in a flexible, performant manner. Here we describe the structure of this format, its performance characteristics, as well as an open-source library support for reading and writing pyramidal OME-TIFFs

Towards a national strategy for digital pathology in Switzerland.

Precision medicine is entering a new era of digital diagnostics; the availability of integrated digital pathology (DP) and structured clinical datasets has the potential to become a key catalyst for biomedical research, education and business development. In Europe, national programs for sharing of this data will be crucial for the development, testing, and validation of machine learning-enabled tools supporting clinical decision-making. Here, the Swiss Digital Pathology Consortium (SDiPath) discusses the creation of a Swiss Digital Pathology Infrastructure (SDPI), which aims to develop a unified national DP network bringing together the Swiss Personalized Health Network (SPHN) with Swiss university hospitals and subsequent inclusion of cantonal and private institutions. This effort builds on existing developments for the national implementation of structured pathology reporting. Opening this national infrastructure and data to international researchers in a sequential rollout phase can enable the large-scale integration of health data and pooling of resources for research purposes and clinical trials. Therefore, the concept of a SDPI directly synergizes with the priorities of the European Commission communication on the digital transformation of healthcare on an international level, and with the aims of the Swiss State Secretariat for Economic Affairs (SECO) for advancing research and innovation in the digitalization domain. SDPI directly addresses the needs of existing national and international research programs in neoplastic and non-neoplastic diseases by providing unprecedented access to well-curated clinicopathological datasets for the development and implementation of novel integrative methods for analysis of clinical outcomes and treatment response. In conclusion, a SDPI would facilitate and strengthen inter-institutional collaboration in technology, clinical development, business and research at a national and international scale, promoting improved patient care via precision medicine

A high-throughput active contour scheme for segmentation of histopathological imagery

In this paper a minimally interactive high-throughput system which employs a color gradient based active contour model for rapid and accurate segmentation of multiple target objects on very large images is presented. While geodesic active contours (GAC) have become very popular tools for image segmentation, they tend to be sensitive to model initialization. A second limitation of GAC models is that the edge detector function typically involves use of gray scale gradients; color images usually being converted to gray scale, prior to gradient computation. For color images, however, the gray scale gradient image results in broken edges and weak boundaries, since the other channels are not exploited in the gradient computation. To cope with these limitations, we present a new GAC model that is driven by an accurate and rapid object initialization scheme; hierarchical normalized cuts (HNCut). HNCut draws its strength from the integration of two powerful segmentation strategies-mean shift clustering and normalized cuts. HNCut involves first defining a color swatch (typically a few pixels) from the object of interest. A multi-scale, mean shift coupled normalized cuts algorithm then rapidly yields an initial accurate detection of all objects in the scene corresponding to the colors in the swatch. This detection result provides the initial contour for a GAC model. The edge-detector function of the GAC model employs a local structure tensor based color gradient, obtained by calculating the local min/max variations contributed from each color channel. We show that the color gradient based edge-detector function results in more prominent boundaries compared to the classical gray scale gradient based function. By integrating the HNCut initialization scheme with color gradient based GAC (CGAC), HNCut-CGAC embodies five unique and novel attributes: (1) efficiency in segmenting multiple target structures; (2) the ability to segment multiple objects from very large images; (3) minimal human interaction; (4) accuracy; and (5) reproducibility. A quantitative and qualitative comparison of the HNCut-CGAC model against other state of the art active contour schemes (including a Hybrid Active Contour model (Paragios-Deriche) and a region-based AC model (Rousson-Deriche)), across 196 digitized prostate histopathology images, suggests that HNCut-CGAC is able to outperform state of the art hybrid and region based AC techniques. Our results show that HNCut-CGAC is computationally efficient and may be easily applied to a variety of different problems and applications. (C) 2011 Elsevier B.V. All rights reserved