IMILIA: interpretable multiple instance learning for inflammation prediction in IBD from H&E whole slide images

As the therapeutic target for Inflammatory Bowel Disease (IBD) shifts toward histologic remission, the accurate assessment of microscopic inflammation has become increasingly central for evaluating disease activity and response to treatment. In this work, we introduce IMILIA (Interpretable Multiple Instance Learning for Inflammation Analysis), an end-to-end framework designed for the prediction of inflammation presence in IBD digitized slides stained with hematoxylin and eosin (H&E), followed by the automated computation of markers characterizing tissue regions driving the predictions. IMILIA is composed of an inflammation prediction module, consisting of a Multiple Instance Learning (MIL) model, and an interpretability module, divided in two blocks: HistoPLUS, for cell instance detection, segmentation and classification; and EpiSeg, for epithelium segmentation. IMILIA achieves a cross-validation ROC-AUC of 0.83 on the discovery cohort, and a ROC-AUC of 0.99 and 0.84 on two external validation cohorts. The interpretability module yields biologically consistent insights: tiles with higher predicted scores show increased densities of immune cells (lymphocytes, plasmocytes, neutrophils and eosinophils), whereas lower-scored tiles predominantly contain normal epithelial cells. Notably, these patterns were consistent across all datasets. Code and models to partially replicate the results on the public IBDColEpi dataset can be found at https://github.com/owkin/imilia.

Towards Comprehensive Cellular Characterisation of H&E slides

Cell detection, segmentation and classification are essential for analyzing tumor microenvironments (TME) on hematoxylin and eosin (H&E) slides. Existing methods suffer from poor performance on understudied cell types (rare or not present in public datasets) and limited cross-domain generalization. To address these shortcomings, we introduce HistoPLUS, a state-of-the-art model for cell analysis, trained on a novel curated pan-cancer dataset of 108,722 nuclei covering 13 cell types. In external validation across 4 independent cohorts, HistoPLUS outperforms current state-of-the-art models in detection quality by 5.2% and overall F1 classification score by 23.7%, while using 5x fewer parameters. Notably, HistoPLUS unlocks the study of 7 understudied cell types and brings significant improvements on 8 of 13 cell types. Moreover, we show that HistoPLUS robustly transfers to two oncology indications unseen during training. To support broader TME biomarker research, we release the model weights and inference code at https://github.com/owkin/histoplus/.

CARMIL: Context-Aware Regularization on Multiple Instance Learning models for Whole Slide Images

Multiple Instance Learning (MIL) models have proven effective for cancer prognosis from Whole Slide Images. However, the original MIL formulation incorrectly assumes the patches of the same image to be independent, leading to a loss of spatial context as information flows through the network. Incorporating contextual knowledge into predictions is particularly important given the inclination for cancerous cells to form clusters and the presence of spatial indicators for tumors. State-of-the-art methods often use attention mechanisms eventually combined with graphs to capture spatial knowledge. In this paper, we take a novel and transversal approach, addressing this issue through the lens of regularization. We propose Context-Aware Regularization for Multiple Instance Learning (CARMIL), a versatile regularization scheme designed to seamlessly integrate spatial knowledge into any MIL model. Additionally, we present a new and generic metric to quantify the Context-Awareness of any MIL model when applied to Whole Slide Images, resolving a previously unexplored gap in the field. The efficacy of our framework is evaluated for two survival analysis tasks on glioblastoma (TCGA GBM) and colon cancer data (TCGA COAD).