From Histopathology Images to Cell Clouds: Learning Slide Representations with Hierarchical Cell Transformer

It is clinically crucial and potentially very beneficial to be able to analyze and model directly the spatial distributions of cells in histopathology whole slide images (WSI). However, most existing WSI datasets lack cell-level annotations, owing to the extremely high cost over giga-pixel images. Thus, it remains an open question whether deep learning models can directly and effectively analyze WSIs from the semantic aspect of cell distributions. In this work, we construct a large-scale WSI dataset with more than 5 billion cell-level annotations, termed WSI-Cell5B, and a novel hierarchical Cell Cloud Transformer (CCFormer) to tackle these challenges. WSI-Cell5B is based on 6,998 WSIs of 11 cancers from The Cancer Genome Atlas Program, and all WSIs are annotated per cell by coordinates and types. To the best of our knowledge, WSI-Cell5B is the first WSI-level large-scale dataset integrating cell-level annotations. On the other hand, CCFormer formulates the collection of cells in each WSI as a cell cloud and models cell spatial distribution. Specifically, Neighboring Information Embedding (NIE) is proposed to characterize the distribution of cells within the neighborhood of each cell, and a novel Hierarchical Spatial Perception (HSP) module is proposed to learn the spatial relationship among cells in a bottom-up manner. The clinical analysis indicates that WSI-Cell5B can be used to design clinical evaluation metrics based on counting cells that effectively assess the survival risk of patients. Extensive experiments on survival prediction and cancer staging show that learning from cell spatial distribution alone can already achieve state-of-the-art (SOTA) performance, i.e., CCFormer strongly outperforms other competing methods.

From Pixels to Gigapixels: Bridging Local Inductive Bias and Long-Range Dependencies with Pixel-Mamba

Histopathology plays a critical role in medical diagnostics, with whole slide images (WSIs) offering valuable insights that directly influence clinical decision-making. However, the large size and complexity of WSIs may pose significant challenges for deep learning models, in both computational efficiency and effective representation learning. In this work, we introduce Pixel-Mamba, a novel deep learning architecture designed to efficiently handle gigapixel WSIs. Pixel-Mamba leverages the Mamba module, a state-space model (SSM) with linear memory complexity, and incorporates local inductive biases through progressively expanding tokens, akin to convolutional neural networks. This enables Pixel-Mamba to hierarchically combine both local and global information while efficiently addressing computational challenges. Remarkably, Pixel-Mamba achieves or even surpasses the quantitative performance of state-of-the-art (SOTA) foundation models that were pretrained on millions of WSIs or WSI-text pairs, in a range of tumor staging and survival analysis tasks, {\bf even without requiring any pathology-specific pretraining}. Extensive experiments demonstrate the efficacy of Pixel-Mamba as a powerful and efficient framework for end-to-end WSI analysis.