digital pathology software developers

Abstract: Joint nuclei instance segmentation and classification requires precise boundaries and neighborhood information that helps distinguish morphologically similar cell types. We present TME-ContextNet, a multi-task framework that learns class-conditioned spatial context from existing nuclear annotations and organizes decoding into geometry-related and semantic task groups. Class-conditioned spatial supervision extends nuclear labels into a dense target using Euclidean distance transforms, requiring no additional tissue-region annotation. We derive its nearest-region interpretation and characterize its stability to small annotation perturbations. A local--global context module combines dilated convolution and self-attention, while a grouped task decoder reduces redundant computation. The spatial head supplies training supervision and is omitted during inference. Experiments on PanMix, CoNSeP, and PanNuke yield Dice scores of 80.23%, 65.32%, and 79.13%, and mean multi-class panoptic quality (mPQ+) scores of 67.62%, 35.50%, and 43.74%, respectively. PanNuke results are averaged across three test folds. Target and decoder controls support the combination of distance-based supervision and grouped decoding while identifying their dependence on task configuration. The framework uses 36.40 million parameters, compared with 54.74 million for HoVer-Net. These findings support a compact, context-aware formulation for joint nuclei analysis in computational pathology.

Abstract: Accurate nuclei instance segmentation is essential for quantitative renal pathology, yet general-purpose models often struggle with low contrast, dense nuclei, complex morphology, and strong background staining. In this work, we extended a human-in-the-loop framework by combining 5,901 foundation-model-generated pseudo-labels from well-segmented cases (Easy), 860 newly expert-annotated unresolved challenging cases (Medium), and 198 expert-annotated consensus failure cases (Hard). These annotations, spanning different levels of segmentation difficulty, enabled the systematic evaluation of seven single-source and mixed-source fine-tuning strategies across nine cell segmentation model configurations. Fine-tuning improved all models, with Medium data included in seven of the nine best-performing strategies. LSP-DETR achieved the highest F1 score of 0.8725 with Hard-only fine-tuning, while StarDist showed the largest improvement, increasing from 0.7380 to 0.8332 with Medium-only fine-tuning. These findings show that annotations spanning multiple difficulty levels support effective model adaptation, although the optimal annotation composition remains model dependent.

Abstract: Gastric Adenocarcinoma is a leading cause of cancer mortality. Although "Inflamed/Non-Inflamed" subtypes have been proposed to predict immunotherapy response, their identification relies on a costly 10-gene RNA signature. We propose a Cross-modal Contrastive Multiple Instance Learning (CCMIL) framework for cross-modal retrieval, imputing these molecular signatures directly from standard Hematoxylin & Eosin (H&E) slides. By leveraging a supervised contrastive objective, CCMIL aligns visual morphological patterns with molecular phenotypes into a shared latent space. This establishes an interpretable search-by-case retrieval engine, enabling pathologists to query a whole slide image to surface transcriptomically coherent neighbors and approximate RNA signatures without genomic sequencing at inference. Our results demonstrate that this retrieval-first approach captures the continuous phenotypic spectrum of tumor inflammation and yields clinically interpretable attention heatmaps. Furthermore, the learned representation also supports competitive downstream classification, providing a practical molecular pre-screening strategy.

Abstract: Histological whole-slide images (WSIs) are central to computational pathology but pose severe computational challenges due to their extremely high resolution, often spanning several gigabytes per slide. To enable scalable learning, existing methods apply self-supervised data condensation to reduce computational cost, but typically rely on heuristic prototype learning and do not explicitly preserve learning-relevant feature distributions for downstream tasks. In response, we introduce a principled reformulation of WSI condensation as a distribution-matching problem under a fixed representational lens, and develop NICER, a tractable approximation framework based on a nonparametric prior with slide-adaptive capacity. Experiments on five histopathology datasets, together with clinical evaluation from a board-certified pathologist, show that NICER consistently outperforms prior methods, achieving an average accuracy improvement of 7.44% while offering improved efficiency-accuracy trade-offs, highlighting the benefits of principled, distribution-aware condensation for scalable histological representation learning. Source codes are available in https://github.com/nmduonggg/NICER.

Abstract: Predicting gene expression from H&E-stained histology images offers a scalable alternative to costly spatial transcriptomics, yet most existing methods operate at the spot level, where signals from multiple cells are aggregated and critical cellular heterogeneity is obscured. Extending this paradigm to single-cell resolution is non-trivial. Naively applying pathology foundation models faces a scale mismatch: their patch-level representations mix multiple cells, whereas per-cell cropping or resizing distorts morphology and removes local context. Conversely, segmentation-based models without strong pretrained visual encoders often lack the morphological representation capacity needed for accurate molecular prediction and inherit errors from imperfect cell boundary masks. Here, we present CELLO, an efficient end-to-end framework that performs a single pathology foundation model forward pass per image and uses grid sampling to extract location-specific features for all cells simultaneously. We further introduce a distance-decay cross-attention module that refines each cell representation using spatially biased local morphological context. Using 52 public Xenium-H&E pairs from HEST-1k that span 12 organs and approximately 10 million cells, CELLO improves the average predictive accuracy over the evaluated baselines while reducing the mean whole-slide inference time compared to DeepSpot2Cell, a 14.0x speed-up on average that excludes upstream cell segmentation. Our work establishes a scalable foundation for single-cell gene expression prediction from H&E images.

Abstract: Pretrained biomedical vision-language models achieve strong zero-shot performance in biomedical image classification. However, downstream biomedical classification often depends on subtle visual differences between classes that may not be fully captured by pretrained representations. Few-shot adaptation addresses this mismatch by optimizing a task-specific predictor on a small labeled support set. Because the selected examples capture only part of the visual variation within the target classes, the adapted predictions can depend strongly on their composition. We propose Prompt-Anchored Residual Adaptation (PARA), which retains the frozen prompt prediction as a support-invariant semantic anchor and incorporates a visual prediction learned from the support set through an anchor-relative residual. The residual step is computed in a closed form from frozen support embeddings using anchor discrepancy and support agreement. Support-set dependence also limits evaluation: comparisons are fair within a shared draw but remain conditional on its composition. To obtain more reliable comparisons, we introduce a repeated-support protocol that separates support-selection variation from optimization randomness and reports both average and worst-20% performance. PARA achieves state-of-the-art performance in both few-shot classification and base-to-novel generalization.

Abstract: Automating the analysis of whole-slide images (WSIs), a key step in cancer diagnosis, has high clinical value, as it can reduce pathologist's workload while improving diagnosis accuracy. Recently, vision-language models have shown promising performance for patch-level classification without requiring any annotation, yet these zero-shot (ZS) predictions remain noisy on fine-grained tasks and must be further refined. A promising direction is to refine all predictions jointly, i.e., a transductive approach. However, most existing methods are not tailored to WSIs. We thus propose SlideTIM, an adaptation to WSIs of the recent transductive approach LC-TIM, which introduces a combined spatial--latent regularizer together with a prior on the patch class distribution. The former enforces spatially and semantically close patches to receive the same predictions, while the prior calibrates the predicted class proportions. Together, they address the complex spatial organization and the strong class imbalance of WSIs. Evaluated on four histology datasets, SlideTIM consistently outperforms all TIM variants, improving the macro-F1 by +8.1pp over the best competing baseline at 1 shot. Compared to the ZS, it raises the macro-F1 by +19.4pp at 1 shot. The code will be made available after submission.