Mitotic Figures
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1 paper in the last four weeks, against 2 the four weeks before. 0.0% of all new papers.
Latest papers 14
Mitotic counting is an important component of tumour grading, diagnosis and prognostic assessment across several tumour types, but manual assessment is time-consuming and subject to inter-pathologist variability. To help address these challenges, we developed MitPro, an AI tool designed to improve consistency and efficiency by directing pathologists towards regions with the highest predicted mitotic activity and highlighting mitotic figures for review, while retaining pathologist control over region selection and the final count. We evaluated its effect on the reproducibility and efficiency of mitotic counting in a retrospective, non-interventional, paired reader study comprising 385 whole-slide images from 3 centres in 3 countries and 7 tumour types using 3 different scanners. 13 pathologists participated, with each slide assessed independently by 3 pathologists without AI assistance and again with AI assistance after a minimum 2 week washout period. Across all slides, AI-assisted counting increased the intraclass correlation coefficient from 0.589 to 0.949. Mean pathologist-level median assessment time decreased from 286.4 to 127.8 seconds, corresponding to an average saving of 151.8 seconds per assessment. Improvements in agreement and efficiency were also observed in supporting analyses using HALO AP and Sectra image management systems and in 2 additional tumour types outside the main study population. AI-assisted assessment was associated with a subtle shift towards higher mitotic counts and scores, consistent with identification of more active mitotic hotspots and fewer missed mitotic figures. The frequency of score change between unassisted and AI-assisted assessment was comparable with inter-pathologist variation during routine counting. These findings support the use of MitPro as an assistive tool for more consistent and efficient mitotic assessment in routine practice.
MiTHras: Task-specific Hierarchical Semi-supervised Contrastive Masked Autoencoder for Mitotic Figure Analysis
Mitotic figure (MF) analysis supports tumor grading and prognostic assessment, but automated models remain sensitive to differences in tissue type and image acquisition. We present MiTHras, a task-specific pretraining framework that combines pseudo-label-guided image- and token-level contrastive learning with masked reconstruction. We construct TCGA-MF-Pseudo, a corpus of 1.8 million cell-centered images from 14 TCGA cohorts spanning 11 organ sites. Comprehensive evaluation on MF classification, detection, count-based survival prediction, and subtype classification demonstrates the efficacy of MiTHras. It achieves the highest mean F1 on all three MF classification benchmarks and both subtype benchmarks. MiTHras also outperforms general-purpose and pathology foundation encoders by a larger margin under frozen-encoder linear probing than under full fine-tuning. Although detection gains are modest due to a shared candidate-detection stage, ablations confirm that token-level supervision improves typical-versus-atypical classification and linear probing. These findings establish that MiTHras yields robust, transferable representations for automated mitotic activity assessment.
Retrieval-Augmented Vision Foundation Models for Robust Leukemia Cell Classification across Multiple Microscopy Datasets
Leukemia cell image classification is challenged by real-world domain shifts from acquisition, staining, illumination, and site protocols, causing single-dataset models to generalize poorly in real clinical scenarios. This work presents a robust framework for leukemia classification across multiple heterogeneous datasets using a two-stage pipeline with a pretrained vision foundation model. Stage 1 performs binary classification (leukemia vs. non-leukemia) and is trained using 122,167 single-cell images. Stage 2 is conditionally applied to Stage 1 positives to perform subtype classification into Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML), trained using 69,400 single-cell images. Labels are harmonized across five heterogeneous datasets to enable cross-dataset training, and performance is evaluated on a held-out dataset protocol to assess domain-shift generalization. Within this pipeline, three encoders are benchmarked (DinoBloom, pretrained on single-cell images; BiomedCLIP, pretrained on biomedical data; and CLIP as a general-purpose model) under linear probing, Low-Rank Adaptation (LoRA), and a Retrieval-Augmented Classification (RAC) module that retrieves the top-k most similar cell images to provide cytomorphological grounding. The objective is to quantify how much domain-specific pretraining contributes to performance under domain shift, and whether cost-effective adaptation and retrieval can be a viable alternative to expensive domain-specialized pretraining. The held-out protocol additionally serves as a diagnostic tool, revealing when classification performance is attributable to dataset-specific artifacts rather than to cytomorphological features.
From Multi-Resolution Cells to Gigapixel Whole Slide Images Foundation Model for Computational Pathology
Vision Transformers (ViTs) and their hierarchical variants have achieved strong performance in Computational Pathology (CPath). However, most are pre-trained on single-resolution Whole Slide Images (WSIs), limiting their generalization across arbitrary resolutions. Gigapixel WSIs inherently contain diagnostic patterns at multiple scales, including cellular morphologies, tissue architectures, and global context, mirroring how expert pathologists examine WSIs. We introduce Multi-Resolution Pyramid Transformer (MRPT), a model that hierarchically aggregates multi-resolution information from cellular to tissue and WSI levels. MRPT employs a biologically meaningful Consecutive Cross-Resolution Attention (CCRA) mechanism to capture scale-independent interactions and enforces multi-resolution semantic consistency by aligning embeddings across resolutions, yielding robust and generalizable WSI representations. Pre-trained in a multi-resolution self-supervised manner on 624M patches, 2.4M regions, and 36K WSIs, MRPT learns rich coarse-to-fine histopathology features. Extensive experiments on 34 diverse datasets show that MRPT surpasses recent foundation models and Multimodal Large Language Models (MLLMs) in cancer subtype classification, tissue phenotyping, and Visual Question Answering (VQA) for WSI understanding.
Beyond Classification: Pathology Foundation Models as Detection Encoders for Mitotic Figures
Pathology foundation models (FMs) are models trained on vast amounts of typically unlabeled data and have been shown to yield regularized latent spaces that can be used effectively in downstream classification tasks. This is also true for the classification of mitotic figures vs. other cells. However, it is so far unclear if the latent space of current FMs provides features that are discriminant and spatially suitably resolved to also serve as a backbone for dense object detection paradigms. In this work, we investigate this question for common current pathology FMs (UNI, UNI2-h, Virchow, Virchow2, H-optimus-0, H-optimus-1) and compare their performance against a fully end-to-end trained baseline based on a ResNet50 architecture. We combine FM backbones with representatives of single stage, dual stage and self-attention-based detectors (RetinaNet, Faster R-CNN, Deformable DETR respectively) on the multi-domain MIDOG++ dataset, and on the TUPAC16 dataset as an out-of-domain case. We show that the H-optimus-0 and Virchow models yielded competitive performance, indicating that the latent spaces of current FMs, all trained on image-level self-supervision, are suitable for direct mitotic figure detection and may be slightly more robust on our out-of-domain test case. All code is made available publicly at https://github.com/DeepMicroscopy/FM4MFdet.
The Giant Hippocampus: From Structural Monoculture to a System of Systems
AI researchers describe state-of-the-art models as one thing repeated at scale: the Transformer, wired identically for text, pixels, or speech. Neuroscientists describe the cortex as a mosaic - dense Layer 4 in visual cortex for spatial encoding, thick Layers 5/6 in motion cortex for temporal integration - different jobs solved by different structures. This paper argues the gap is a structural error, not a stylistic one, and is measurable. A century of cytoarchitecture, from Brodmann to single-cell Patch-seq, shows distinct cognitive functions are implemented by qualitatively different structures, not by rescaling one template. The convolutional neural network is the field's own proof: local receptive fields and hierarchical depth encoded this prior directly, reaching strong image recognition on far less data than later architectures needed. The paper traces how this lesson was discarded: the "Hardware Lottery" made the Transformer the path of least resistance, not the principled choice, and Mixture-of-Experts, often cited as diversity, in fact partitions parameters among identical experts. A functionalist analysis shows the Transformer is best understood as a functional analog of the hippocampal formation, not a general-purpose cortex - the same mistake as treating cortex as one giant Broca's area, except the field has now standardized on a giant hippocampus, applied to tasks it was never built for: audition, executive gating, working memory. The paper closes with an alternative: a Heterogeneous Topological Network, a System of Systems in which distinct modules keep the inductive bias their computation demands and communicate through standardized interfaces. This is a design discipline for AI architects, not cognitive science: specify modularity before training, using structural evidence as a design input rather than reverse-engineering architecture from a trained model's behavior.
EMBRACE: A Multi-task Framework for Comprehensive Quality Assessment in Cleavage-stage Embryo
Cleavage-stage embryo assessment in in vitro fertilization requires the integrated interpretation of cytoplasmic fragmentation, developmental stage, and blastomere symmetry. However, conventional visual assessment is affected by observer variability, particularly when fragmented regions are small, irregular, or low contrast. This study presents EMBRACE, a multi-task deep learning framework for jointly performing cytoplasmic-fragmentation segmentation, t2/t4 developmental-stage classification, and blastomere-symmetry grading from static cleavage-stage embryo microscopy images. EMBRACE combines a shared ResNet-50 backbone, a concatenation-based multi-scale feature-fusion (C-MSFF) module, a U-Net-style segmentation decoder, and two task-specific classification heads. After predefined inclusion and exclusion criteria, 9,137 annotated embryo images were divided into 7,309 training, 914 validation, and 914 held-out test images. On the held-out test set, EMBRACE achieved a Dice coefficient of 0.781 and an intersection over union of 0.677 for fragmentation segmentation. Developmental-stage classification achieved an accuracy of 0.995, macro-F1 of 0.994, and AUC of 1.000. Blastomere-symmetry grading achieved a balanced accuracy of 0.901, macro-F1 of 0.907, and quadratic weighted kappa of 0.859. These findings support the feasibility of combining spatially inspectable fragmentation localization with embryo-level morphology assessment in a single framework. External and prospective validation is required before clinical deployment.
CurvSegFlow: Time-Conditioned Flow Matching for Robust Segmentation of Curvilinear Structures in Noisy Biomedical Images
Accurate segmentation of curvilinear structures remains challenging in biomedical imaging due to their thin geometry, complex topology, and sensitivity to noise. This is particularly critical for microscopy images of cytoskeletal network, where low signal-to-noise ratios and dense filament crossings often lead to fragmented or inaccurate segmentation. In this work, we propose CurvSegFlow, a segmentation framework based on time-conditioned flow matching. Instead of predicting a segmentation mask in a single pass, the method models segmentation as a dynamic process that progressively refines a noisy initialization into the target structure through a learned velocity field. The proposed model combines a U-Net backbone with triple-term loss function and temporal embeddings to guide the refinement process across reconstruction stages. This formulation enables gradual error correction and improves the continuity of thin structures. CurvSegFlow is evaluated on multiple synthetic and real microtubule datasets, as well as on public benchmarks of retinal vessels, corneal nerves and coronary arteries. Across datasets, the method achieves competitive or superior performance compared to established segmentation models, with consistent improvements in precision and structural continuity, particularly under low signal-to-noise conditions. These results show that flow-based iterative refinement provides a robust and general framework for curvilinear structure segmentation. Overall, the proposed approach improves segmentation quality in challenging imaging conditions and generalizes effectively across modalities without architectural changes.
Robust Image-Driven Phenotyping of Ovarian Tumor Cells using Optimized Dynamic Features in Hyperbolic Channels
Label-free, image-based cellular mechanophenotyping in microfluidic devices provides a high-throughput method for single-cell profiling. However, while complex microchannels (e.g., hyperbolic geometries) reveal transient deformation dynamics under continuous extensional stress, the resulting high-dimensional feature spaces are highly susceptible to hydrodynamic artifacts. Flow rate variations often distort discriminative boundaries, linking feature distributions to fluid conditions rather than intrinsic biology. To overcome this, we introduce a stability-guided analytical framework that decouples flow-induced noise from authentic mechanobiological signatures. We tracked the morphodynamic, kinematic, and intracellular optical-density trajectories of healthy and malignant ovarian cells to build a 93-dimensional feature space. Using a cross-flow screening strategy based on structural consistency and statistical persistence, we isolated robust descriptors, creating task-adapted subsets (20 features for binary classification; 25 for cancer subtyping). Variance-attribution analysis confirmed the neutralization of flow-conditioned artifacts; notably, flow-associated variance in the primary principal component fell from 69.9% to 9.3% in the subtyping task. We also found that macroscopic binary discrimination depends on bulk kinematic transitions, while clonal subtyping requires localized intracellular optical heterogeneity. These optimized subsets maintained diagnostic fidelity across multiple machine learning architectures and restricted sampling conditions. This framework establishes a robust, flow-independent foundation for continuous dynamic phenotyping.
Mitosis Detection in the Wild: Multi-Tumor and Context-Aware Generalization in the MIDOG 2025 Challenge
Automated mitosis detection is a well-established task in computational pathology. While previous benchmarks focused on scanner-induced domain shift, clinical "real-world" application requires models to be robust across the vast variance to be expected in the histological landscape. The MItosis DOmain Generalization (MIDOG) 2025 challenge was designed to evaluate algorithmic performance across unprecedented biological and contextual diversity. We curated a test dataset of 365 cases, encompassing 12 distinct human, canine and feline tumor types, digitized across multiple scanning platforms. Moving beyond hand-selected hotspots, the challenge required detection also in random tissue areas (representative of the whole slide detection situation) and challenging areas (areas rich in hard negatives). In the second track, we introduced the classification of atypical mitotic figures (AMFs). There were 18 teams submitting to the detection track, with F1 scores ranging up to 0.740. In the AMF detection track, we had 21 submissions with balanced accuracy values up to 0.908. Our analysis reveals that while most models perform reliably in traditional hotspots, significant performance degradation occurs in challenging ROIs, where false positive rates tripled. Furthermore, performance varied significantly across the 12 tumor types, highlighting "blind spots" in current state-of-the-art architectures when encountering rare or highly pleomorphic malignancies. Moreover, we evaluated the effectiveness of ensembling and found a mean increases of 1.5 and 1.3 percentage points in F1 score and balanced accuracy, respectively. In contrast, TTA showed no relevant improvement. MIDOG 2025 demonstrates that "in the wild" mitosis detection remains a significant hurdle. The transition from hotspot-only evaluation to a multi-contextual framework provides a more realistic proxy for clinical reliability.
CP-Agent: Context-Aware Multimodal Reasoning for Cellular Morphological Profiling under Chemical Perturbations
Cell Painting combines multiplexed fluorescent staining, high-content imaging, and quantitative analysis to generate high-dimensional phenotypic readouts to support diverse downstream tasks such as mechanism-of-action (MoA) inference, toxicity prediction, and construction of drug-disease atlases. However, existing workflows are slow, costly and difficult to interpret. Approaches for drug screening modeling predominantly focus on molecular representation learning, while neglecting actual experimental context (e.g., cell line, dosing schedule, etc.), limiting generalization and MoA resolution. We introduce CP-Agent, an agentic multimodal large language model (MLLM) capable of generating mechanism-relevant, human-interpretable rationales for cell morphological changes under drug perturbations. At its core, CP-Agent leverages a context-aware alignment module, CP-CLIP, that jointly embeds high-content images and experimental metadata to enable robust treatment and MoA discrimination (achieving a maximum F1-score of 0.896). By integrating CP-CLIP outputs with agentic tool usage and reasoning, CP-Agent compiles rationales into a structured report to guide experimental design and hypothesis refinement. These capabilities highlight CP-Agent's potential to accelerate drug discovery by enabling more interpretable, scalable, and context-aware phenotypic screening -- streamlining iterative cycles of hypothesis generation in drug discovery.
Aycromo: An Open-Source Platform for Automatic Chromosome Detection in Metaphase Images Based on Deep Learning
Chromosome analysis is a fundamental step in the diagnosis of genetic diseases, but the manual karyotyping workflow is time-consuming and heavily dependent on expert specialists, often requiring several days per patient. Although Deep Learning models have achieved high performance in chromosome detection, most proposed solutions remain restricted to research prototypes or lack graphical interfaces suitable for clinical use. In this work, we present Aycromo, an open-source desktop platform for AI-assisted cytogenetic analysis. Built on Electron and ONNX Runtime, the tool allows cytogeneticists to load pre-trained models, compare architectures through an integrated benchmarking module, and manually correct detections via an interactive annotation interface, all without command-line interaction. Preliminary experiments on metaphase images from the CRCN-NE dataset demonstrate that YOLOv11 achieves 99.40% mAP@50, while the platform reduces per-slide analysis to seconds
CytoCLIP: Learning Cytoarchitectural Characteristics in Developing Human Brain Using Contrastive Language Image Pre-Training
The functions of different regions of the human brain are closely linked to their distinct cytoarchitecture, which is defined by the spatial arrangement and morphology of the cells. Identifying brain regions by their cytoarchitecture enables various scientific analyses of the brain. However, delineating these areas manually in brain histological sections is time-consuming and requires specialized knowledge. An automated approach is necessary to minimize the effort needed from human experts. To address this, we propose CytoCLIP, a suite of vision-language models derived from pre-trained Contrastive Language-Image Pre-Training (CLIP) frameworks to learn joint visual-text representations of brain cytoarchitecture. CytoCLIP comprises two model variants: one is trained using low-resolution whole-region images to understand the overall cytoarchitectural pattern of an area, and the other is trained on high-resolution image tiles for detailed cellular-level representation. The training dataset is created from NISSL-stained histological sections of developing fetal brains of different gestational weeks. It includes 86 distinct regions for low-resolution images and 379 brain regions for high-resolution tiles. We evaluate the model's understanding of the cytoarchitecture and generalization ability using region classification and cross-modal retrieval tasks. Multiple experiments are performed under various data setups, including data from samples of different ages and sectioning planes. Experimental results demonstrate that CytoCLIP outperforms existing methods. It achieves a weighted F1 score of 0.87 for whole-region classification and 0.91 for high-resolution image tile classification.
Towards Cellular-Scale Interpretability in Pathology Foundation Models for Biomarker Assessment
Molecular biomarker testing in pathology is often costly and tissue-consuming, limiting scalable clinical deployment. Artificial intelligence applied to hematoxylin and eosin (HE)-stained histology could enable rapid biomarker screening, but clinical translation requires models that are both accurate and interpretable. Here we introduce Hireca, a biomarker-focused pathology foundation model pretrained on more than 80,000 whole-slide images spanning 38 organ types from three medical centers, together with CytoMap, an interpretability module that localizes cellular-scale evidence underlying predictions. Across 10 biomarker tasks encompassing morphological, molecular, genetic, and spatial-transcriptomic-proxy readouts, Hireca ranked first in five tasks and outperformed comparable models overall. In evaluation by eight pathologists from two countries, CytoMap was consistently preferred over alternative visualization approaches and revealed error patterns in difficult cases. These results position Hireca and CytoMap as a transparent framework for clinically reviewable biomarker assessment directly from routine HE histology.