SToFM: a Multi-scale Foundation Model for Spatial Transcriptomics

Spatial Transcriptomics (ST) technologies provide biologists with rich insights into single-cell biology by preserving spatial context of cells. Building foundational models for ST can significantly enhance the analysis of vast and complex data sources, unlocking new perspectives on the intricacies of biological tissues. However, modeling ST data is inherently challenging due to the need to extract multi-scale information from tissue slices containing vast numbers of cells. This process requires integrating macro-scale tissue morphology, micro-scale cellular microenvironment, and gene-scale gene expression profile. To address this challenge, we propose SToFM, a multi-scale Spatial Transcriptomics Foundation Model. SToFM first performs multi-scale information extraction on each ST slice, to construct a set of ST sub-slices that aggregate macro-, micro- and gene-scale information. Then an SE(2) Transformer is used to obtain high-quality cell representations from the sub-slices. Additionally, we construct \textbf{SToCorpus-88M}, the largest high-resolution spatial transcriptomics corpus for pretraining. SToFM achieves outstanding performance on a variety of downstream tasks, such as tissue region semantic segmentation and cell type annotation, demonstrating its comprehensive understanding of ST data

Adaptive Attention Residual U-Net for curvilinear structure segmentation in fluorescence microscopy and biomedical images

Segmenting curvilinear structures in fluorescence microscopy remains a challenging task, particularly under noisy conditions and in dense filament networks commonly seen in vivo. To address this, we created two original datasets consisting of hundreds of synthetic images of fluorescently labelled microtubules within cells. These datasets are precisely annotated and closely mimic real microscopy images, including realistic noise. The second dataset presents an additional challenge, by simulating varying fluorescence intensities along filaments that complicate segmentation. While deep learning has shown strong potential in biomedical image analysis, its performance often declines in noisy or low-contrast conditions. To overcome this limitation, we developed a novel advanced architecture: the Adaptive Squeeze-and-Excitation Residual U-Net (ASE_Res_UNet). This model enhanced the standard U-Net by integrating residual blocks in the encoder and adaptive SE attention mechanisms in the decoder. Through ablation studies and comprehensive visual and quantitative evaluations, ASE_Res_UNet consistently outperformed its variants, namely standard U-Net, ASE_UNet and Res_UNet architectures. These improvements, particularly in noise resilience and detecting fine, low-intensity structures, were largely attributed to the adaptive SE attention module that we created. We further benchmarked ASE_Res_UNet against various state-of-the-art models, and found it achieved superior performance on our most challenging dataset. Finally, the model also generalized well to real microscopy images of stained microtubules as well as to other curvilinear structures. Indeed, it successfully segmented retinal blood vessels and nerves in noisy or low-contrast biomedical images, demonstrating its strong potential for applications in disease diagnosis and treatment.

Continual Multiple Instance Learning with Enhanced Localization for Histopathological Whole Slide Image Analysis

Multiple instance learning (MIL) significantly reduced annotation costs via bag-level weak labels for large-scale images, such as histopathological whole slide images (WSIs). However, its adaptability to continual tasks with minimal forgetting has been rarely explored, especially on instance classification for localization. Weakly incremental learning for semantic segmentation has been studied for continual localization, but it focused on natural images, leveraging global relationships among hundreds of small patches (e.g., $16 \times 16$) using pre-trained models. This approach seems infeasible for MIL localization due to enormous amounts ($\sim 10^5$) of large patches (e.g., $256 \times 256$) and no available global relationships such as cancer cells. To address these challenges, we propose Continual Multiple Instance Learning with Enhanced Localization (CoMEL), an MIL framework for both localization and adaptability with minimal forgetting. CoMEL consists of (1) Grouped Double Attention Transformer (GDAT) for efficient instance encoding, (2) Bag Prototypes-based Pseudo-Labeling (BPPL) for reliable instance pseudo-labeling, and (3) Orthogonal Weighted Low-Rank Adaptation (OWLoRA) to mitigate forgetting in both bag and instance classification. Extensive experiments on three public WSI datasets demonstrate superior performance of CoMEL, outperforming the prior arts by up to $11.00\%$ in bag-level accuracy and up to $23.4\%$ in localization accuracy under the continual MIL setup.

The Four Color Theorem for Cell Instance Segmentation

Cell instance segmentation is critical to analyzing biomedical images, yet accurately distinguishing tightly touching cells remains a persistent challenge. Existing instance segmentation frameworks, including detection-based, contour-based, and distance mapping-based approaches, have made significant progress, but balancing model performance with computational efficiency remains an open problem. In this paper, we propose a novel cell instance segmentation method inspired by the four-color theorem. By conceptualizing cells as countries and tissues as oceans, we introduce a four-color encoding scheme that ensures adjacent instances receive distinct labels. This reformulation transforms instance segmentation into a constrained semantic segmentation problem with only four predicted classes, substantially simplifying the instance differentiation process. To solve the training instability caused by the non-uniqueness of four-color encoding, we design an asymptotic training strategy and encoding transformation method. Extensive experiments on various modes demonstrate our approach achieves state-of-the-art performance. The code is available at https://github.com/zhangye-zoe/FCIS.

InceptionMamba: Efficient Multi-Stage Feature Enhancement with Selective State Space Model for Microscopic Medical Image Segmentation

Accurate microscopic medical image segmentation plays a crucial role in diagnosing various cancerous cells and identifying tumors. Driven by advancements in deep learning, convolutional neural networks (CNNs) and transformer-based models have been extensively studied to enhance receptive fields and improve medical image segmentation task. However, they often struggle to capture complex cellular and tissue structures in challenging scenarios such as background clutter and object overlap. Moreover, their reliance on the availability of large datasets for improved performance, along with the high computational cost, limit their practicality. To address these issues, we propose an efficient framework for the segmentation task, named InceptionMamba, which encodes multi-stage rich features and offers both performance and computational efficiency. Specifically, we exploit semantic cues to capture both low-frequency and high-frequency regions to enrich the multi-stage features to handle the blurred region boundaries (e.g., cell boundaries). These enriched features are input to a hybrid model that combines an Inception depth-wise convolution with a Mamba block, to maintain high efficiency and capture inherent variations in the scales and shapes of the regions of interest. These enriched features along with low-resolution features are fused to get the final segmentation mask. Our model achieves state-of-the-art performance on two challenging microscopic segmentation datasets (SegPC21 and GlaS) and two skin lesion segmentation datasets (ISIC2017 and ISIC2018), while reducing computational cost by about 5 times compared to the previous best performing method.

PixCell: A generative foundation model for digital histopathology images

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

Unsupervised cell segmentation by fast Gaussian Processes

Cell boundary information is crucial for analyzing cell behaviors from time-lapse microscopy videos. Existing supervised cell segmentation tools, such as ImageJ, require tuning various parameters and rely on restrictive assumptions about the shape of the objects. While recent supervised segmentation tools based on convolutional neural networks enhance accuracy, they depend on high-quality labelled images, making them unsuitable for segmenting new types of objects not in the database. We developed a novel unsupervised cell segmentation algorithm based on fast Gaussian processes for noisy microscopy images without the need for parameter tuning or restrictive assumptions about the shape of the object. We derived robust thresholding criteria adaptive for heterogeneous images containing distinct brightness at different parts to separate objects from the background, and employed watershed segmentation to distinguish touching cell objects. Both simulated studies and real-data analysis of large microscopy images demonstrate the scalability and accuracy of our approach compared with the alternatives.

Moment kernels: a simple and scalable approach for equivariance to rotations and reflections in deep convolutional networks

The principle of translation equivariance (if an input image is translated an output image should be translated by the same amount), led to the development of convolutional neural networks that revolutionized machine vision. Other symmetries, like rotations and reflections, play a similarly critical role, especially in biomedical image analysis, but exploiting these symmetries has not seen wide adoption. We hypothesize that this is partially due to the mathematical complexity of methods used to exploit these symmetries, which often rely on representation theory, a bespoke concept in differential geometry and group theory. In this work, we show that the same equivariance can be achieved using a simple form of convolution kernels that we call ``moment kernels,'' and prove that all equivariant kernels must take this form. These are a set of radially symmetric functions of a spatial position $x$, multiplied by powers of the components of $x$ or the identity matrix. We implement equivariant neural networks using standard convolution modules, and provide architectures to execute several biomedical image analysis tasks that depend on equivariance principles: classification (outputs are invariant under orthogonal transforms), 3D image registration (outputs transform like a vector), and cell segmentation (quadratic forms defining ellipses transform like a matrix).

VideoMolmo: Spatio-Temporal Grounding Meets Pointing

Spatio-temporal localization is vital for precise interactions across diverse domains, from biological research to autonomous navigation and interactive interfaces. Current video-based approaches, while proficient in tracking, lack the sophisticated reasoning capabilities of large language models, limiting their contextual understanding and generalization. We introduce VideoMolmo, a large multimodal model tailored for fine-grained spatio-temporal pointing conditioned on textual descriptions. Building upon the Molmo architecture, VideoMolmo incorporates a temporal module utilizing an attention mechanism to condition each frame on preceding frames, ensuring temporal consistency. Additionally, our novel temporal mask fusion pipeline employs SAM2 for bidirectional point propagation, significantly enhancing coherence across video sequences. This two-step decomposition, i.e., first using the LLM to generate precise pointing coordinates, then relying on a sequential mask-fusion module to produce coherent segmentation, not only simplifies the task for the language model but also enhances interpretability. Due to the lack of suitable datasets, we curate a comprehensive dataset comprising 72k video-caption pairs annotated with 100k object points. To evaluate the generalization of VideoMolmo, we introduce VPoS-Bench, a challenging out-of-distribution benchmark spanning five real-world scenarios: Cell Tracking, Egocentric Vision, Autonomous Driving, Video-GUI Interaction, and Robotics. We also evaluate our model on Referring Video Object Segmentation (Refer-VOS) and Reasoning VOS tasks. In comparison to existing models, VideoMolmo substantially improves spatio-temporal pointing accuracy and reasoning capability. Our code and models are publicly available at https://github.com/mbzuai-oryx/VideoMolmo.

IRS: Incremental Relationship-guided Segmentation for Digital Pathology

Continual learning is rapidly emerging as a key focus in computer vision, aiming to develop AI systems capable of continuous improvement, thereby enhancing their value and practicality in diverse real-world applications. In healthcare, continual learning holds great promise for continuously acquired digital pathology data, which is collected in hospitals on a daily basis. However, panoramic segmentation on digital whole slide images (WSIs) presents significant challenges, as it is often infeasible to obtain comprehensive annotations for all potential objects, spanning from coarse structures (e.g., regions and unit objects) to fine structures (e.g., cells). This results in temporally and partially annotated data, posing a major challenge in developing a holistic segmentation framework. Moreover, an ideal segmentation model should incorporate new phenotypes, unseen diseases, and diverse populations, making this task even more complex. In this paper, we introduce a novel and unified Incremental Relationship-guided Segmentation (IRS) learning scheme to address temporally acquired, partially annotated data while maintaining out-of-distribution (OOD) continual learning capacity in digital pathology. The key innovation of IRS lies in its ability to realize a new spatial-temporal OOD continual learning paradigm by mathematically modeling anatomical relationships between existing and newly introduced classes through a simple incremental universal proposition matrix. Experimental results demonstrate that the IRS method effectively handles the multi-scale nature of pathological segmentation, enabling precise kidney segmentation across various structures (regions, units, and cells) as well as OOD disease lesions at multiple magnifications. This capability significantly enhances domain generalization, making IRS a robust approach for real-world digital pathology applications.