Do Pathology Foundation Models Encode Disease Progression? A Pseudotime Analysis of Visual Representations
Pritika Vig, Ren-Chin Wu, William Lotter
原文摘要
Vision foundation models trained on discretely sampled images achieve strong performance on classification benchmarks, yet whether their representations encode the continuous processes underlying their training data remains unclear. This question is especially pertinent in computational pathology, where we posit that models whose latent representations implicitly capture ordinal disease progression may better reflect underlying biology, support more robust generalization, and enable quantitative analyses of features associated with disease transitions. Using diffusion pseudotime, a method developed to infer developmental trajectories from single-cell transcriptomics, we probe whether foundation models organize disease states along coherent progression directions in representation space. Across four cancer progressions and six models, we find that all pathology-specific models recover trajectory orderings significantly exceeding null baselines, with pathology vision-only models achieving the highest average fidelities. Model rankings by trajectory fidelity on reference diseases predict few-shot classification performance on held-out diseases ($ρ= 0.91$), and exploratory analysis shows cell-type composition varies along inferred trajectories in patterns consistent with known stromal remodeling. Together, these results suggest that vision foundation models can implicitly learn to represent continuous processes from independent static observations, and that trajectory fidelity provides a complementary measure of representation quality beyond downstream performance. While demonstrated in pathology, this framework could be applied to other domains where continuous processes are observed through static snapshots.
cs.CV