Mixed Magnification Aggregation for Generalizable Region-Level Representations in Computational Pathology

In recent years, a standard computational pathology workflow has emerged where whole slide images are cropped into tiles, these tiles are processed using a foundation model, and task-specific models are built using the resulting representations. At least 15 different foundation models have been proposed, and the vast majority are trained exclusively with tiles using the 20$\times$ magnification. However, it is well known that certain histologic features can only be discerned with larger context windows and requires a pathologist to zoom in and out when analyzing a whole slide image. Furthermore, creating 224$\times$224 pixel crops at 20$\times$ leads to a large number of tiles per slide, which can be gigapixel in size. To more accurately capture multi-resolution features and investigate the possibility of reducing the number of representations per slide, we propose a region-level mixing encoder. Our approach jointly fuses image tile representations of a mixed magnification foundation model using a masked embedding modeling pretraining step. We explore a design space for pretraining the proposed mixed-magnification region aggregators and evaluate our models on transfer to biomarker prediction tasks representing various cancer types. Results demonstrate cancer dependent improvements in predictive performance, highlighting the importance of spatial context and understanding.

DPVis: Visual Exploration of Disease Progression Pathways

Clinical researchers use disease progression modeling algorithms to predict future patient status and characterize progression patterns. One approach for disease progression modeling is to describe patient status using a small number of states that represent distinctive distributions over a set of observed measures. Hidden Markov models (HMMs) and its variants are a class of models that both discover these states and make predictions concerning future states for new patients. HMMs can be trained using longitudinal observations of subjects from large-scale cohort studies, clinical trials, and electronic health records. Despite the advantages of using the algorithms for discovering interesting patterns, it still remains challenging for medical experts to interpret model outputs, complex modeling parameters, and clinically make sense of the patterns. To tackle this problem, we conducted a design study with physician scientists, statisticians, and visualization experts, with the goal to investigate disease progression pathways of certain chronic diseases, namely type 1 diabetes (T1D), Huntington's disease, Parkinson's disease, and chronic obstructive pulmonary disease (COPD). As a result, we introduce DPVis which seamlessly integrates model parameters and outcomes of HMMs into interpretable, and interactive visualizations. In this study, we demonstrate that DPVis is successful in evaluating disease progression models, visually summarizing disease states, interactively exploring disease progression patterns, and designing and comparing clinically relevant subgroup cohorts by introducing a case study on observation data from clinical studies of T1D.