Nucleus detection in histopathology whole slide images (WSIs) is crucial for a broad spectrum of clinical applications. The gigapixel size of WSIs necessitates the use of sliding window methodology for nucleus detection. However, mainstream methods process each sliding window independently, which overlooks broader contextual information and easily leads to inaccurate predictions. To address this limitation, recent studies additionally crop a large Filed-of-View (LFoV) patch centered on each sliding window to extract contextual features. However, such methods substantially increase whole-slide inference latency. In this work, we propose an effective and efficient context-aware nucleus detection approach. Specifically, instead of using lFoV patches, we aggregate contextual clues from off-the-shelf features of historically visited sliding windows, which greatly enhances the inference efficiency. Moreover, compared to lFoV patches used in previous works, the sliding window patches have higher magnification and provide finer-grained tissue details, thereby enhancing the classification accuracy. To develop the proposed context-aware model, we utilize annotated patches along with their surrounding unlabeled patches for training. Beyond exploiting high-level tissue context from these surrounding regions, we design a post-training strategy that leverages abundant unlabeled nucleus samples within them to enhance the model's context adaptability. Extensive experimental results on three challenging benchmarks demonstrate the superiority of our method.

The emergence of large multimodal models (LMMs) has brought significant advancements to pathology. Previous research has primarily focused on separately training patch-level and whole-slide image (WSI)-level models, limiting the integration of learned knowledge across patches and WSIs and resulting in redundant models. In this work, we introduce CPath-Omni, the first 15B parameter LMM that unifies patch and WSI analysis, consolidating a variety of tasks at both levels, including classification, visual question answering, captioning, and visual referring prompting. Extensive experiments demonstrate that CPath-Omni achieves state-of-the-art (SOTA) performance across seven diverse tasks on 39 out of 42 datasets, outperforming or matching task-specific models trained for individual tasks. Additionally, we develop a specialized pathology CLIP-based visual processor for CPath-Omni, CPath-CLIP, which, for the first time, integrates different vision models and incorporates a large language model as a text encoder to build a more powerful CLIP model, which achieves SOTA performance on nine zero-shot and four few-shot datasets. Our findings highlight CPath-Omni’s ability to unify diverse pathology tasks, demonstrating its potential to streamline and advance the field of foundation model in pathology. The code and model are available at CPath-Omni.

While vision language models (VLMs) excel in 2D semantic visual understanding, their ability to quantitatively reason about 3D spatial relationships remains underexplored due to the deficiency of spatial representation ability of 2D images. In this paper, we analyze the problem hindering VLMs’ spatial understanding abilities and propose SD-VLM, a novel framework that significantly enhances fundamental spatial perception abilities of VLMs through two key contributions: (1) propose Massive Spatial Measuring and Understanding (MSMU) dataset with precise spatial annotations, and (2) introduce a simple depth positional encoding method strengthening VLMs’ spatial awareness. MSMU dataset includes massive quantitative spatial tasks with 700K QA pairs, 2.5M physical numerical annotations, and 10K chain-of-thought augmented samples. We have trained SD-VLM, a strong generalist VLM which shows superior quantitative spatial measuring and understanding capability. SD-VLM not only achieves state-of-the-art performance on our proposed MSMU-Bench, but also shows spatial generalization abilities on other spatial understanding benchmarks including Q-Spatial and SpatialRGPTBench. Extensive experiments demonstrate that SD-VLM outperforms GPT-4o and Intern-VL3-78B by 26.91% and 25.56% respectively on MSMU-Bench. Code and models are released at https://github.com/cpystan/SD-VLM.

Synthetic data generation emerges as a strategy to mitigate data scarcity in digital pathology, where complicated tissue and cellular features are correlated with cancer diagnosis. The synthesis of such visuals, however, suffers from limited inter class diversity and scarcity of cellular annotations. Current methodologies struggle with capturing the broad spectrum of pathology features, causing unpredictable objects and defected fidelity. Moreover, discrepancies in image resolution across developmental and operational phases can amplify the distribution shifts, undermining the precision of diagnosis. To address these challenges, we introduce TOpology guided PathOlogy Foundation Model (ToPoFM), a visual foundation model designed for the synthesis of high-resolution pathology images with cellular-level control. Our approach integrates a topology-informed cell arrangement generator to steer large language models for crafting synthetic cell arrangements. We correlate cell arrangement guidance with diffusion model for pathology content generation, then further implement a random sliding inference strategy, merging discrete low-resolution samplings into single high-resolution representation. Our model requires only small patches for training. The efficacy of ToPoFM is demonstrated through extensive experiments, complemented by expert validations, showing high fidelity on data synthesis. Additionally, we underscore the utility of our generated imagery as an augmentation tool, enhancing the performance of downstream tasks, including cancer subtype classification and segmentation.

Point-based cell detection (PCD), which pursues high-performance cell sensing under low-cost data annotation, has garnered increased attention in computational pathology community. Unlike mainstream PCD methods that rely on intermediate density map representations, the Point-to-Point network (P2PNet) has recently emerged as an end-to-end solution for PCD, demonstrating impressive cell detection accuracy and efficiency. Nevertheless, P2PNet is limited to decoding from a single-level feature map due to the scale-agnostic property of point proposals, which is insufficient to leverage multi-scale information. Moreover, the spatial distribution of pre-set point proposals is biased from that of cells, leading to inaccurate cell localization. To lift these limitations, we present DPA-P2PNet in this work. The proposed method directly extracts multi-scale features for decoding according to the coordinates of point proposals on hierarchical feature maps. On this basis, we further devise deformable point proposals to mitigate the positional bias between proposals and potential cells to promote cell localization. Inspired by practical pathological diagnosis that usually combines high-level tissue structure and low-level cell morphology for accurate cell classification, we propose a multi-field-of-view (mFoV) variant of DPA-P2PNet to accommodate additional large FoV images with tissue information as model input. Finally, we execute the first self-supervised pre-training on immunohistochemistry histopathology image data and evaluate the suitability of four representative self-supervised methods on the PCD task. Experimental results on three benchmarks and a large-scale and real-world interval dataset demonstrate the superiority of our proposed models over the state-of-the-art counterparts. Codes and pre-trained weights are available at https://github.com/windygoo/DPA-P2PNet.

In digital pathology, cancer lesions are identified by analyzing the spatial context within pathology images. Synthesizing such complex spatial context is challenging as pathology whole slide images typically exhibit high resolution, low inter-class variety, and are sparsely labeled. To address these challenges, we propose PathUp, a novel diffusion model tailored for the synthesis of multi-class high-resolution pathology images. Our approach includes a latent space patch-wise timestep tracking, which helps to generate high-quality images without tiling artifacts. Pathology knowledge is integrated through our patho-align. The robust generation of lesion subtypes and scale information is ensured by introducing a feature entropy loss. The effectiveness of our method is evaluated through extensive experiments, supplemented by assessments from human experts, demonstrating the authenticity of the synthetic data produced. Furthermore, we highlight the potential utility of our generated images as an augmentation method, thereby enhancing the performance of downstream tasks such as cancer subtype classification.

Histopathology Whole Slide Image (WSI) analysis serves as the gold standard for clinical cancer diagnosis in the daily routines of doctors. To develop computer-aided diagnosis model for histopathology WSIs, previous methods typically employ Multi-Instance Learning to enable slide-level prediction given only slide-level labels. Among these models, vanilla attention mechanisms without pairwise interactions have traditionally been employed but are unable to model contextual information. More recently, self-attention models have been utilized to address this issue. To alleviate the computational complexity of long sequences in large WSIs, methods like HIPT use region-slicing, and TransMIL employs Nystr\"{o}mformer as an approximation of full self-attention. Both approaches suffer from suboptimal performance due to the loss of key information. Moreover, their use of absolute positional embedding struggles to effectively handle long contextual dependencies in shape-varying WSIs. In this paper, we first analyze how the low-rank nature of the long-sequence attention matrix constrains the representation ability of WSI modelling. Then, we demonstrate that the rank of attention matrix can be improved by focusing on local interactions via a local attention mask. Our analysis shows that the local mask aligns with the attention patterns in the lower layers of the Transformer. Furthermore, the local attention mask can be implemented during chunked attention calculation, reducing the quadratic computational complexity to linear with a small local bandwidth. Additionally, this locality helps the model generalize to unseen or under-fitted positions more easily. Building on this, we propose a local-global hybrid Transformer for both computational acceleration and local-global information interactions modelling. Our method, Long-contextual MIL (LongMIL), is evaluated through extensive experiments on various WSI tasks to validate its superiority in: 1) overall performance, 2) memory usage and speed, and 3) extrapolation ability compared to previous methods.

With the advancement of deep learning, computer-assisted clinical diagnosis, such as liquid-based cervical cytology, has attracted more attention. However, the fragile robustness of deep learning models has a non-negligible impact on their classification accuracy and reliability. To be more specific, various scanner parameters will be used depending on the pathologist’s preferences during the clinical diagnosis process (e.g., field source brightness, contrast, saturation, etc.), and this variation will lead to the unstable performance of the model. In this paper, we construct an evaluation pathway to assess the stability and consistency of deep learning models under various customized scanner parameters. Specifically, a multi-scanned dataset consists of 4200 whole slide images (WSIs) is generated by scanning 200 stained slices using various scanner parameters. Moreover, we conducted a large number of experiments to investigate the robustness of numerous models, including convolution-based and transformer-based models concerning various scanner parameter settings. Furthermore, we introduce several indicators to analyze the prediction accuracy, consistency and robustness of the model on the constructed dataset. The experimental results indicate that the deep learning models are sensitive to luminance-related scanner parameters. In addition, transformer-based models have better robustness than traditional convolutional neural networks. Our code has been made available1.