Visinity: Visual Spatial Neighborhood Analysis for Multiplexed Tissue Imaging Data.

New highly-multiplexed imaging technologies have enabled the study of tissues in unprecedented detail. These methods are increasingly being applied to understand how cancer cells and immune response change during tumor development, progression, and metastasis, as well as following treatment. Yet, existing analysis approaches focus on investigating small tissue samples on a per-cell basis, not taking into account the spatial proximity of cells, which indicates cell-cell interaction and specific biological processes in the larger cancer microenvironment. We present Visinity, a scalable visual analytics system to analyze cell interaction patterns across cohorts of whole-slide multiplexed tissue images. Our approach is based on a fast regional neighborhood computation, leveraging unsupervised learning to quantify, compare, and group cells by their surrounding cellular neighborhood. These neighborhoods can be visually analyzed in an exploratory and confirmatory workflow. Users can explore spatial patterns present across tissues through a scalable image viewer and coordinated views highlighting the neighborhood composition and spatial arrangements of cells. To verify or refine existing hypotheses, users can query for specific patterns to determine their presence and statistical significance. Findings can be interactively annotated, ranked, and compared in the form of small multiples. In two case studies with biomedical experts, we demonstrate that Visinity can identify common biological processes within a human tonsil and uncover novel white-blood cell networks and immune-tumor interactions.

Scope2Screen: Focus+Context Techniques for Pathology Tumor Assessment in Multivariate Image Data.

Inspection of tissues using a light microscope is the primary method of diagnosing many diseases, notably cancer. Highly multiplexed tissue imaging builds on this foundation, enabling the collection of up to 60 channels of molecular information plus cell and tissue morphology using antibody staining. This provides unique insight into disease biology and promises to help with the design of patient-specific therapies. However, a substantial gap remains with respect to visualizing the resulting multivariate image data and effectively supporting pathology workflows in digital environments on screen. We, therefore, developed Scope2Screen, a scalable software system for focus+context exploration and annotation of whole-slide, high-plex, tissue images. Our approach scales to analyzing 100GB images of 109 or more pixels per channel, containing millions of individual cells. A multidisciplinary team of visualization experts, microscopists, and pathologists identified key image exploration and annotation tasks involving finding, magnifying, quantifying, and organizing regions of interest (ROIs) in an intuitive and cohesive manner. Building on a scope-to-screen metaphor, we present interactive lensing techniques that operate at single-cell and tissue levels. Lenses are equipped with task-specific functionality and descriptive statistics, making it possible to analyze image features, cell types, and spatial arrangements (neighborhoods) across image channels and scales. A fast sliding-window search guides users to regions similar to those under the lens; these regions can be analyzed and considered either separately or as part of a larger image collection. A novel snapshot method enables linked lens configurations and image statistics to be saved, restored, and shared with these regions. We validate our designs with domain experts and apply Scope2Screen in two case studies involving lung and colorectal cancers to discover cancer-relevant image features.