IEEE Trans Vis Comput Graph. 2023 Jan;29(1):106-116. doi: 10.1109/TVCG.2022.3209378. Epub 2022 Dec 16.
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.
新的高度多重化成像技术使研究组织细节成为可能。这些方法越来越多地被用于了解癌细胞和免疫反应在肿瘤发展、进展和转移过程中以及治疗后的变化。然而,现有的分析方法侧重于逐个细胞地研究小的组织样本,而没有考虑到细胞的空间邻近性,这表明细胞间的相互作用和更大的癌症微环境中的特定生物学过程。我们提出了 Visinity,这是一种可扩展的可视化分析系统,用于分析整个幻灯片多重化组织图像队列中的细胞相互作用模式。我们的方法基于快速的区域邻域计算,利用无监督学习来量化、比较和根据其周围细胞邻域对细胞进行分组。这些邻域可以在探索性和验证性工作流程中进行可视化分析。用户可以通过可扩展的图像查看器和突出显示细胞邻域组成和空间排列的协调视图来探索组织中存在的空间模式。为了验证或完善现有的假设,用户可以查询特定模式以确定其存在和统计显著性。发现可以以小倍数的形式进行交互式注释、排名和比较。在与生物医学专家的两项案例研究中,我们证明了 Visinity 可以识别人扁桃体中的常见生物学过程,并揭示新的白细胞网络和免疫-肿瘤相互作用。