HistoSmith: Single-Stage Histology Image-Label Generation via Conditional Latent Diffusion for Enhanced Cell Segmentation and Classification

Precise segmentation and classification of cell instances are vital for analyzing the tissue microenvironment in histology images, supporting medical diagnosis, prognosis, treatment planning, and studies of brain cytoarchitecture. However, the creation of high-quality annotated datasets for training remains a major challenge. This study introduces a novel single-stage approach (HistoSmith) for generating image-label pairs to augment histology datasets. Unlike state-of-the-art methods that utilize diffusion models with separate components for label and image generation, our approach employs a latent diffusion model to learn the joint distribution of cellular layouts, classification masks, and histology images. This model enables tailored data generation by conditioning on user-defined parameters such as cell types, quantities, and tissue types. Trained on the Conic H&E histopathology dataset and the Nissl-stained CytoDArk0 dataset, the model generates realistic and diverse labeled samples. Experimental results demonstrate improvements in cell instance segmentation and classification, particularly for underrepresented cell types like neutrophils in the Conic dataset. These findings underscore the potential of our approach to address data scarcity challenges.

CASC-AI: Consensus-aware Self-corrective AI Agents for Noise Cell Segmentation

Multi-class cell segmentation in high-resolution gigapixel whole slide images (WSI) is crucial for various clinical applications. However, training such models typically requires labor-intensive, pixel-wise annotations by domain experts. Recent efforts have democratized this process by involving lay annotators without medical expertise. However, conventional non-agent-based approaches struggle to handle annotation noise adaptively, as they lack mechanisms to mitigate false positives (FP) and false negatives (FN) at both the image-feature and pixel levels. In this paper, we propose a consensus-aware self-corrective AI agent that leverages the Consensus Matrix to guide its learning process. The Consensus Matrix defines regions where both the AI and annotators agree on cell and non-cell annotations, which are prioritized with stronger supervision. Conversely, areas of disagreement are adaptively weighted based on their feature similarity to high-confidence agreement regions, with more similar regions receiving greater attention. Additionally, contrastive learning is employed to separate features of noisy regions from those of reliable agreement regions by maximizing their dissimilarity. This paradigm enables the AI to iteratively refine noisy labels, enhancing its robustness. Validated on one real-world lay-annotated cell dataset and two simulated noisy datasets, our method demonstrates improved segmentation performance, effectively correcting FP and FN errors and showcasing its potential for training robust models on noisy datasets. The official implementation and cell annotations are publicly available at https://github.com/ddrrnn123/CASC-AI.

Generalizable Reinforcement Learning with Biologically Inspired Hyperdimensional Occupancy Grid Maps for Exploration and Goal-Directed Path Planning

Real-time autonomous systems utilize multi-layer computational frameworks to perform critical tasks such as perception, goal finding, and path planning. Traditional methods implement perception using occupancy grid mapping (OGM), segmenting the environment into discretized cells with probabilistic information. This classical approach is well-established and provides a structured input for downstream processes like goal finding and path planning algorithms. Recent approaches leverage a biologically inspired mathematical framework known as vector symbolic architectures (VSA), commonly known as hyperdimensional computing, to perform probabilistic OGM in hyperdimensional space. This approach, VSA-OGM, provides native compatibility with spiking neural networks, positioning VSA-OGM as a potential neuromorphic alternative to conventional OGM. However, for large-scale integration, it is essential to assess the performance implications of VSA-OGM on downstream tasks compared to established OGM methods. This study examines the efficacy of VSA-OGM against a traditional OGM approach, Bayesian Hilbert Maps (BHM), within reinforcement learning based goal finding and path planning frameworks, across a controlled exploration environment and an autonomous driving scenario inspired by the F1-Tenth challenge. Our results demonstrate that VSA-OGM maintains comparable learning performance across single and multi-scenario training configurations while improving performance on unseen environments by approximately 47%. These findings highlight the increased generalizability of policy networks trained with VSA-OGM over BHM, reinforcing its potential for real-world deployment in diverse environments.

Cell Nuclei Detection and Classification in Whole Slide Images with Transformers

Accurate and efficient cell nuclei detection and classification in histopathological Whole Slide Images (WSIs) are pivotal for digital pathology applications. Traditional cell segmentation approaches, while commonly used, are computationally expensive and require extensive post-processing, limiting their practicality for high-throughput clinical settings. In this paper, we propose a paradigm shift from segmentation to detection for extracting cell information from WSIs, introducing CellNuc-DETR as a more effective solution. We evaluate the accuracy performance of CellNuc-DETR on the PanNuke dataset and conduct cross-dataset evaluations on CoNSeP and MoNuSeg to assess robustness and generalization capabilities. Our results demonstrate state-of-the-art performance in both cell nuclei detection and classification tasks. Additionally, we assess the efficiency of CellNuc-DETR on large WSIs, showing that it not only outperforms current methods in accuracy but also significantly reduces inference times. Specifically, CellNuc-DETR is twice as fast as the fastest segmentation-based method, HoVer-NeXt, while achieving substantially higher accuracy. Moreover, it surpasses CellViT in accuracy and is approximately ten times more efficient in inference speed on WSIs. These results establish CellNuc-DETR as a superior approach for cell analysis in digital pathology, combining high accuracy with computational efficiency.

Mind the Gap: Evaluating Patch Embeddings from General-Purpose and Histopathology Foundation Models for Cell Segmentation and Classification

Recent advancements in foundation models have transformed computer vision, driving significant performance improvements across diverse domains, including digital histopathology. However, the advantages of domain-specific histopathology foundation models over general-purpose models for specialized tasks such as cell analysis remain underexplored. This study investigates the representation learning gap between these two categories by analyzing multi-level patch embeddings applied to cell instance segmentation and classification. We implement an encoder-decoder architecture with a consistent decoder and various encoders. These include convolutional, vision transformer (ViT), and hybrid encoders pre-trained on ImageNet-22K or LVD-142M, representing general-purpose foundation models. These are compared against ViT encoders from the recently released UNI, Virchow2, and Prov-GigaPath foundation models, trained on patches extracted from hundreds of thousands of histopathology whole-slide images. The decoder integrates patch embeddings from different encoder depths via skip connections to generate semantic and distance maps. These maps are then post-processed to create instance segmentation masks where each label corresponds to an individual cell and to perform cell-type classification. All encoders remain frozen during training to assess their pre-trained feature extraction capabilities. Using the PanNuke and CoNIC histopathology datasets, and the newly introduced Nissl-stained CytoDArk0 dataset for brain cytoarchitecture studies, we evaluate instance-level detection, segmentation accuracy, and cell-type classification. This study provides insights into the comparative strengths and limitations of general-purpose vs. histopathology foundation models, offering guidance for model selection in cell-focused histopathology and brain cytoarchitecture analysis workflows.

Geometric Framework for 3D Cell Segmentation Correction

3D cellular image segmentation methods are commonly divided into non-2D-based and 2D-based approaches, the latter reconstructing 3D shapes from the segmentation results of 2D layers. However, errors in 2D results often propagate, leading to oversegmentations in the final 3D results. To tackle this issue, we introduce an interpretable geometric framework that addresses the oversegmentations by correcting the 2D segmentation results based on geometric information from adjacent layers. Leveraging both geometric (layer-to-layer, 2D) and topological (3D shape) features, we use binary classification to determine whether neighboring cells should be stitched. We develop a pre-trained classifier on public plant cell datasets and validate its performance on animal cell datasets, confirming its effectiveness in correcting oversegmentations under the transfer learning setting. Furthermore, we demonstrate that our framework can be extended to correcting oversegmentation on non-2D-based methods. A clear pipeline is provided for end-users to build the pre-trained model to any labeled dataset.

Single cell resolution 3D imaging and segmentation within intact live tissues

Epithelial cells form diverse structures from squamous spherical organoids to densely packed pseudostratified tissues. Quantification of cellular properties in these contexts requires high-resolution deep imaging and computational techniques to achieve truthful three-dimensional (3D) structural features. Here, we describe a detailed step-by-step protocol for sample preparation, imaging and deep-learning-assisted cell segmentation to achieve accurate quantification of fluorescently labelled individual cells in 3D within live tissues. We share the lessons learned through troubleshooting 3D imaging of Drosophila wing discs, including considerations on the choice of microscopy modality and settings (objective, sample mounting) and available segmentation methods. In addition, we include a computational pipeline alongside custom code to assist replication of the protocol. While we focus on the segmentation of cell outlines from membrane labelling, this protocol applies to a wide variety of samples, and we believe it be valuable for studying other tissues that demand complex analysis in 3D.

scBIT: Integrating Single-cell Transcriptomic Data into fMRI-based Prediction for Alzheimer's Disease Diagnosis

Functional MRI (fMRI) and single-cell transcriptomics are pivotal in Alzheimer's disease (AD) research, each providing unique insights into neural function and molecular mechanisms. However, integrating these complementary modalities remains largely unexplored. Here, we introduce scBIT, a novel method for enhancing AD prediction by combining fMRI with single-nucleus RNA (snRNA). scBIT leverages snRNA as an auxiliary modality, significantly improving fMRI-based prediction models and providing comprehensive interpretability. It employs a sampling strategy to segment snRNA data into cell-type-specific gene networks and utilizes a self-explainable graph neural network to extract critical subgraphs. Additionally, we use demographic and genetic similarities to pair snRNA and fMRI data across individuals, enabling robust cross-modal learning. Extensive experiments validate scBIT's effectiveness in revealing intricate brain region-gene associations and enhancing diagnostic prediction accuracy. By advancing brain imaging transcriptomics to the single-cell level, scBIT sheds new light on biomarker discovery in AD research. Experimental results show that incorporating snRNA data into the scBIT model significantly boosts accuracy, improving binary classification by 3.39% and five-class classification by 26.59%. The codes were implemented in Python and have been released on GitHub (https://github.com/77YQ77/scBIT) and Zenodo (https://zenodo.org/records/11599030) with detailed instructions.

CellViT++: Energy-Efficient and Adaptive Cell Segmentation and Classification Using Foundation Models

Digital Pathology is a cornerstone in the diagnosis and treatment of diseases. A key task in this field is the identification and segmentation of cells in hematoxylin and eosin-stained images. Existing methods for cell segmentation often require extensive annotated datasets for training and are limited to a predefined cell classification scheme. To overcome these limitations, we propose $\text{CellViT}^{{\scriptscriptstyle ++}}$, a framework for generalized cell segmentation in digital pathology. $\text{CellViT}^{{\scriptscriptstyle ++}}$ utilizes Vision Transformers with foundation models as encoders to compute deep cell features and segmentation masks simultaneously. To adapt to unseen cell types, we rely on a computationally efficient approach. It requires minimal data for training and leads to a drastically reduced carbon footprint. We demonstrate excellent performance on seven different datasets, covering a broad spectrum of cell types, organs, and clinical settings. The framework achieves remarkable zero-shot segmentation and data-efficient cell-type classification. Furthermore, we show that $\text{CellViT}^{{\scriptscriptstyle ++}}$ can leverage immunofluorescence stainings to generate training datasets without the need for pathologist annotations. The automated dataset generation approach surpasses the performance of networks trained on manually labeled data, demonstrating its effectiveness in creating high-quality training datasets without expert annotations. To advance digital pathology, $\text{CellViT}^{{\scriptscriptstyle ++}}$ is available as an open-source framework featuring a user-friendly, web-based interface for visualization and annotation. The code is available under https://github.com/TIO-IKIM/CellViT-plus-plus.

An Incremental Sampling and Segmentation-Based Approach for Motion Planning Infeasibility

We present a simple and easy-to-implement algorithm to detect plan infeasibility in kinematic motion planning. Our method involves approximating the robot's configuration space to a discrete space, where each degree of freedom has a finite set of values. The obstacle region separates the free configuration space into different connected regions. For a path to exist between the start and goal configurations, they must lie in the same connected region of the free space. Thus, to ascertain plan infeasibility, we merely need to sample adequate points from the obstacle region that isolate start and goal. Accordingly, we progressively construct the configuration space by sampling from the discretized space and updating the bitmap cells representing obstacle regions. Subsequently, we partition this partially built configuration space to identify different connected components within it and assess the connectivity of the start and goal cells. We illustrate this methodology on five different scenarios with configuration spaces having up to 5 degree-of-freedom (DOF).