arXiv subjects

Chenglu Zhu

Publications and source records attributed to Chenglu Zhu.

At least 19 recordsLinked to original sources

arXiv2026

NuNext: Reframing Nucleus Detection as Next-Point Detection

Nucleus detection in histopathology is pivotal for a wide range of clinical applications. Existing approaches either regress nuclear proxy maps that require complex post-processing, or employ dense anchors or queries that introduce severe foreground-background imbalance. In this work, we reformulate nucleus detection as next-point prediction, wherein a multimodal large language model is developed to directly output foreground nucleus centroids from the input image. The model is trained in two stages. In the supervised learning stage, we propose spatial-aware soft supervision to relax strict centroid matching and a chain-of-visual-thought strategy to incorporate visual priors that facilitate coordinate prediction. In the reinforcement fine-tuning stage, we design distribution matching reward, low-variance group filtering, and fine-grained advantage shaping to further improve the model's detection quality. Extensive experiments on nine widely used benchmarks demonstrate the superiority of our method. Code will be released soon.

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arXiv2025

CPathAgent: An Agent-based Foundation Model for Interpretable High-Resolution Pathology Image Analysis Mimicking Pathologists' Diagnostic Logic

Recent advances in computational pathology have led to the emergence of numerous foundation models. These models typically rely on general-purpose encoders with multi-instance learning for whole slide image (WSI) classification or apply multimodal approaches to generate reports directly from images. However, these models cannot emulate the diagnostic approach of pathologists, who systematically examine slides at low magnification to obtain an overview before progressively zooming in on suspicious regions to formulate comprehensive diagnoses. Instead, existing models directly output final diagnoses without revealing the underlying reasoning process. To address this gap, we introduce CPathAgent, an innovative agent-based approach that mimics pathologists' diagnostic workflow by autonomously navigating across WSI based on observed visual features, thereby generating substantially more transparent and interpretable diagnostic summaries. To achieve this, we develop a multi-stage training strategy that unifies patch-level, region-level, and WSI-level capabilities within a single model, which is essential for replicating how pathologists understand and reason across diverse image scales. Additionally, we construct PathMMU-HR2, the first expert-validated benchmark for large region analysis. This represents a critical intermediate scale between patches and whole slides, reflecting a key clinical reality where pathologists typically examine several key large regions rather than entire slides at once. Extensive experiments demonstrate that CPathAgent consistently outperforms existing approaches across benchmarks at three different image scales, validating the effectiveness of our agent-based diagnostic approach and highlighting a promising direction for computational pathology.

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arXiv2025

PathVQ: Reforming Computational Pathology Foundation Model for Whole Slide Image Analysis via Vector Quantization

Computational pathology and whole-slide image (WSI) analysis are pivotal in cancer diagnosis and prognosis. However, the ultra-high resolution of WSIs presents significant modeling challenges. Recent advancements in pathology foundation models have improved performance, yet most approaches rely on [CLS] token representation of tile ViT as slide-level inputs (16x16 pixels is refereed as patch and 224x224 pixels as tile). This discards critical spatial details from patch tokens, limiting downstream WSI analysis tasks. We find that leveraging all spatial patch tokens benefits WSI analysis but incurs nearly 200x higher storage and training costs (e.g., 196 tokens in ViT$_{224}$). To address this, we introduce vector quantized (VQ) distillation on patch feature, which efficiently compresses spatial patch tokens using discrete indices and a decoder. Our method reduces token dimensionality from 1024 to 16, achieving a 64x compression rate while preserving reconstruction fidelity. Furthermore, we employ a multi-scale VQ (MSVQ) strategy, which not only enhances VQ reconstruction performance but also serves as a Self-supervised Learning (SSL) supervision for a seamless slide-level pretraining objective. Built upon the quantized patch features and supervision targets of tile via MSVQ, we develop a progressive convolutional module and slide-level SSL to extract representations with rich spatial-information for downstream WSI tasks. Extensive evaluations on multiple datasets demonstrate the effectiveness of our approach, achieving state-of-the-art performance in WSI analysis. Code will be available soon.

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arXiv2025

Towards Effective and Efficient Context-aware Nucleus Detection in Histopathology Whole Slide Images

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.

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arXiv2024

CPath-Omni: A Unified Multimodal Foundation Model for Patch and Whole Slide Image Analysis in Computational Pathology

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 15-billion-parameter LMM designed to unify both patch and WSI level image 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.

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arXiv2024

Panther: Illuminate the Sight of Multimodal LLMs with Instruction-Guided Visual Prompts

Multimodal large language models (MLLMs) are closing the gap to human visual perception capability rapidly, while, still lag behind on attending to subtle images details or locating small objects precisely, etc. Common schemes to tackle these issues include deploying multiple vision encoders or operating on original high-resolution images. Few studies have concentrated on taking the textual instruction into improving visual representation, resulting in losing focus in some vision-centric tasks, a phenomenon we herein termed as Amblyopia. In this work, we introduce Panther, a MLLM that closely adheres to user instruction and locates targets of interests precisely, with the finesse of a black panther. Specifically, Panther comprises three integral components: Panther-VE, Panther-Bridge, and Panther-Decoder. Panther-VE integrates user instruction information at the early stages of the vision encoder, thereby extracting the most relevant and useful visual representations. The Panther-Bridge module, equipped with powerful filtering capabilities, significantly reduces redundant visual information, leading to a substantial savings in training costs. The Panther-Decoder is versatile and can be employed with any decoder-only architecture of LLMs without discrimination. Experimental results, particularly on vision-centric benchmarks, have demonstrated the effectiveness of Panther.

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arXiv2024

Rethinking Transformer for Long Contextual Histopathology Whole Slide Image Analysis

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 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 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. 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. Our code will be available at github.com/invoker-LL/Long-MIL.

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arXiv2024

Large-scale cervical precancerous screening via AI-assisted cytology whole slide image analysis

Cervical Cancer continues to be the leading gynecological malignancy, posing a persistent threat to women's health on a global scale. Early screening via cytology Whole Slide Image (WSI) diagnosis is critical to prevent this Cancer progression and improve survival rate, but pathologist's single test suffers inevitable false negative due to the immense number of cells that need to be reviewed within a WSI. Though computer-aided automated diagnostic models can serve as strong complement for pathologists, their effectiveness is hampered by the paucity of extensive and detailed annotations, coupled with the limited interpretability and robustness. These factors significantly hinder their practical applicability and reliability in clinical settings. To tackle these challenges, we develop an AI approach, which is a Scalable Technology for Robust and Interpretable Diagnosis built on Extensive data (STRIDE) of cervical cytology. STRIDE addresses the bottleneck of limited annotations by integrating patient-level labels with a small portion of cell-level labels through an end-to-end training strategy, facilitating scalable learning across extensive datasets. To further improve the robustness to real-world domain shifts of cytology slide-making and imaging, STRIDE employs color adversarial samples training that mimic staining and imaging variations. Lastly, to achieve pathologist-level interpretability for the trustworthiness in clinical settings, STRIDE can generate explanatory textual descriptions that simulates pathologists' diagnostic processes by cell image feature and textual description alignment. Conducting extensive experiments and evaluations in 183 medical centers with a dataset of 341,889 WSIs and 0.1 billion cells from cervical cytology patients, STRIDE has demonstrated a remarkable superiority over previous state-of-the-art techniques.

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arXiv2024

WSI-VQA: Interpreting Whole Slide Images by Generative Visual Question Answering

Whole slide imaging is routinely adopted for carcinoma diagnosis and prognosis. Abundant experience is required for pathologists to achieve accurate and reliable diagnostic results of whole slide images (WSI). The huge size and heterogeneous features of WSIs make the workflow of pathological reading extremely time-consuming. In this paper, we propose a novel framework (WSI-VQA) to interpret WSIs by generative visual question answering. WSI-VQA shows universality by reframing various kinds of slide-level tasks in a question-answering pattern, in which pathologists can achieve immunohistochemical grading, survival prediction, and tumor subtyping following human-machine interaction. Furthermore, we establish a WSI-VQA dataset which contains 8672 slide-level question-answering pairs with 977 WSIs. Besides the ability to deal with different slide-level tasks, our generative model which is named Wsi2Text Transformer (W2T) outperforms existing discriminative models in medical correctness, which reveals the potential of our model to be applied in the clinical scenario. Additionally, we also visualize the co-attention mapping between word embeddings and WSIs as an intuitive explanation for diagnostic results. The dataset and related code are available at https://github.com/cpystan/WSI-VQA.

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arXiv2024

PathGen-1.6M: 1.6 Million Pathology Image-text Pairs Generation through Multi-agent Collaboration

Vision Language Models (VLMs) like CLIP have attracted substantial attention in pathology, serving as backbones for applications such as zero-shot image classification and Whole Slide Image (WSI) analysis. Additionally, they can function as vision encoders when combined with large language models (LLMs) to support broader capabilities. Current efforts to train pathology VLMs rely on pathology image-text pairs from platforms like PubMed, YouTube, and Twitter, which provide limited, unscalable data with generally suboptimal image quality. In this work, we leverage large-scale WSI datasets like TCGA to extract numerous high-quality image patches. We then train a large multimodal model to generate captions for these images, creating PathGen-1.6M, a dataset containing 1.6 million high-quality image-caption pairs. Our approach involves multiple agent models collaborating to extract representative WSI patches, generating and refining captions to obtain high-quality image-text pairs. Extensive experiments show that integrating these generated pairs with existing datasets to train a pathology-specific CLIP model, PathGen-CLIP, significantly enhances its ability to analyze pathological images, with substantial improvements across nine pathology-related zero-shot image classification tasks and three whole-slide image tasks. Furthermore, we construct 200K instruction-tuning data based on PathGen-1.6M and integrate PathGen-CLIP with the Vicuna LLM to create more powerful multimodal models through instruction tuning. Overall, we provide a scalable pathway for high-quality data generation in pathology, paving the way for next-generation general pathology models.

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arXiv2024

AEM: Attention Entropy Maximization for Multiple Instance Learning based Whole Slide Image Classification

Multiple Instance Learning (MIL) effectively analyzes whole slide images but faces overfitting due to attention over-concentration. While existing solutions rely on complex architectural modifications or additional processing steps, we introduce Attention Entropy Maximization (AEM), a simple yet effective regularization technique. Our investigation reveals the positive correlation between attention entropy and model performance. Building on this insight, we integrate AEM regularization into the MIL framework to penalize excessive attention concentration. To address sensitivity to the AEM weight parameter, we implement Cosine Weight Annealing, reducing parameter dependency. Extensive evaluations demonstrate AEM's superior performance across diverse feature extractors, MIL frameworks, attention mechanisms, and augmentation techniques. Here is our anonymous code: https://github.com/dazhangyu123/AEM.

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arXiv2024

PathMMU: A Massive Multimodal Expert-Level Benchmark for Understanding and Reasoning in Pathology

The emergence of large multimodal models has unlocked remarkable potential in AI, particularly in pathology. However, the lack of specialized, high-quality benchmark impeded their development and precise evaluation. To address this, we introduce PathMMU, the largest and highest-quality expert-validated pathology benchmark for Large Multimodal Models (LMMs). It comprises 33,428 multimodal multi-choice questions and 24,067 images from various sources, each accompanied by an explanation for the correct answer. The construction of PathMMU harnesses GPT-4V's advanced capabilities, utilizing over 30,000 image-caption pairs to enrich captions and generate corresponding Q&As in a cascading process. Significantly, to maximize PathMMU's authority, we invite seven pathologists to scrutinize each question under strict standards in PathMMU's validation and test sets, while simultaneously setting an expert-level performance benchmark for PathMMU. We conduct extensive evaluations, including zero-shot assessments of 14 open-sourced and 4 closed-sourced LMMs and their robustness to image corruption. We also fine-tune representative LMMs to assess their adaptability to PathMMU. The empirical findings indicate that advanced LMMs struggle with the challenging PathMMU benchmark, with the top-performing LMM, GPT-4V, achieving only a 49.8% zero-shot performance, significantly lower than the 71.8% demonstrated by human pathologists. After fine-tuning, significantly smaller open-sourced LMMs can outperform GPT-4V but still fall short of the expertise shown by pathologists. We hope that the PathMMU will offer valuable insights and foster the development of more specialized, next-generation LMMs for pathology.

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arXiv2024

PathAsst: A Generative Foundation AI Assistant Towards Artificial General Intelligence of Pathology

As advances in large language models (LLMs) and multimodal techniques continue to mature, the development of general-purpose multimodal large language models (MLLMs) has surged, offering significant applications in interpreting natural images. However, the field of pathology has largely remained untapped, particularly in gathering high-quality data and designing comprehensive model frameworks. To bridge the gap in pathology MLLMs, we present PathAsst, a multimodal generative foundation AI assistant to revolutionize diagnostic and predictive analytics in pathology. The development of PathAsst involves three pivotal steps: data acquisition, CLIP model adaptation, and the training of PathAsst's multimodal generative capabilities. Firstly, we collect over 207K high-quality pathology image-text pairs from authoritative sources. Leveraging the advanced power of ChatGPT, we generate over 180K instruction-following samples. Furthermore, we devise additional instruction-following data specifically tailored for invoking eight pathology-specific sub-models we prepared, allowing the PathAsst to effectively collaborate with these models, enhancing its diagnostic ability. Secondly, by leveraging the collected data, we construct PathCLIP, a pathology-dedicated CLIP, to enhance PathAsst's capabilities in interpreting pathology images. Finally, we integrate PathCLIP with the Vicuna-13b and utilize pathology-specific instruction-tuning data to enhance the multimodal generation capacity of PathAsst and bolster its synergistic interactions with sub-models. The experimental results of PathAsst show the potential of harnessing AI-powered generative foundation model to improve pathology diagnosis and treatment processes.

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arXiv2024

Unleashing the Power of Prompt-driven Nucleus Instance Segmentation

Nucleus instance segmentation in histology images is crucial for a broad spectrum of clinical applications. Current dominant algorithms rely on regression of nuclear proxy maps. Distinguishing nucleus instances from the estimated maps requires carefully curated post-processing, which is error-prone and parameter-sensitive. Recently, the Segment Anything Model (SAM) has earned huge attention in medical image segmentation, owing to its impressive generalization ability and promptable property. Nevertheless, its potential on nucleus instance segmentation remains largely underexplored. In this paper, we present a novel prompt-driven framework that consists of a nucleus prompter and SAM for automatic nucleus instance segmentation. Specifically, the prompter learns to generate a unique point prompt for each nucleus while the SAM is fine-tuned to output the corresponding mask for the prompted nucleus. Furthermore, we propose the inclusion of adjacent nuclei as negative prompts to enhance the model's capability to identify overlapping nuclei. Without complicated post-processing, our proposed method sets a new state-of-the-art performance on three challenging benchmarks. Code is available at \url{github.com/windygoo/PromptNucSeg}

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arXiv2023

WsiCaption: Multiple Instance Generation of Pathology Reports for Gigapixel Whole-Slide Images

Whole slide images are the foundation of digital pathology for the diagnosis and treatment of carcinomas. Writing pathology reports is laborious and error-prone for inexperienced pathologists. To reduce the workload and improve clinical automation, we investigate how to generate pathology reports given whole slide images. On the data end, we curated the largest WSI-text dataset (PathText). In specific, we collected nearly 10000 high-quality WSI-text pairs for visual-language models by recognizing and cleaning pathology reports which narrate diagnostic slides in TCGA. On the model end, we propose the multiple instance generative model (MI-Gen) which can produce pathology reports for gigapixel WSIs. We benchmark our model on the largest subset of TCGA-PathoText. Experimental results show our model can generate pathology reports which contain multiple clinical clues and achieve competitive performance on certain slide-level tasks. We observe that simple semantic extraction from the pathology reports can achieve the best performance (0.838 of F1 score) on BRCA subtyping surpassing previous state-of-the-art approaches. Our collected dataset and related code are available.

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arXiv2023

Long-MIL: Scaling Long Contextual Multiple Instance Learning for Histopathology Whole Slide Image Analysis

Histopathology image analysis is the golden standard of clinical diagnosis for Cancers. In doctors daily routine and computer-aided diagnosis, the Whole Slide Image (WSI) of histopathology tissue is used for analysis. Because of the extremely large scale of resolution, previous methods generally divide the WSI into a large number of patches, then aggregate all patches within a WSI by Multi-Instance Learning (MIL) to make the slide-level prediction when developing computer-aided diagnosis tools. However, most previous WSI-MIL models using global-attention without pairwise interaction and any positional information, or self-attention with absolute position embedding can not well handle shape varying large WSIs, e.g. testing WSIs after model deployment may be larger than training WSIs, since the model development set is always limited due to the difficulty of histopathology WSIs collection. To deal with the problem, in this paper, we propose to amend position embedding for shape varying long-contextual WSI by introducing Linear Bias into Attention, and adapt it from 1-d long sequence into 2-d long-contextual WSI which helps model extrapolate position embedding to unseen or under-fitted positions. We further utilize Flash-Attention module to tackle the computational complexity of Transformer, which also keep full self-attention performance compared to previous attention approximation work. Our method, Long-contextual MIL (Long-MIL) are evaluated on extensive experiments including 4 dataset including WSI classification and survival prediction tasks to validate the superiority on shape varying WSIs. The source code will be open-accessed soon.

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arXiv2023

Test-Time Training for Semantic Segmentation with Output Contrastive Loss

Although deep learning-based segmentation models have achieved impressive performance on public benchmarks, generalizing well to unseen environments remains a major challenge. To improve the model's generalization ability to the new domain during evaluation, the test-time training (TTT) is a challenging paradigm that adapts the source-pretrained model in an online fashion. Early efforts on TTT mainly focus on the image classification task. Directly extending these methods to semantic segmentation easily experiences unstable adaption due to segmentation's inherent characteristics, such as extreme class imbalance and complex decision spaces. To stabilize the adaptation process, we introduce contrastive loss (CL), known for its capability to learn robust and generalized representations. Nevertheless, the traditional CL operates in the representation space and cannot directly enhance predictions. In this paper, we resolve this limitation by adapting the CL to the output space, employing a high temperature, and simplifying the formulation, resulting in a straightforward yet effective loss function called Output Contrastive Loss (OCL). Our comprehensive experiments validate the efficacy of our approach across diverse evaluation scenarios. Notably, our method excels even when applied to models initially pre-trained using domain adaptation methods on test domain data, showcasing its resilience and adaptability.\footnote{Code and more information could be found at~ \url{https://github.com/dazhangyu123/OCL}}

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arXiv2023

Attention-Challenging Multiple Instance Learning for Whole Slide Image Classification

In the application of Multiple Instance Learning (MIL) methods for Whole Slide Image (WSI) classification, attention mechanisms often focus on a subset of discriminative instances, which are closely linked to overfitting. To mitigate overfitting, we present Attention-Challenging MIL (ACMIL). ACMIL combines two techniques based on separate analyses for attention value concentration. Firstly, UMAP of instance features reveals various patterns among discriminative instances, with existing attention mechanisms capturing only some of them. To remedy this, we introduce Multiple Branch Attention (MBA) to capture more discriminative instances using multiple attention branches. Secondly, the examination of the cumulative value of Top-K attention scores indicates that a tiny number of instances dominate the majority of attention. In response, we present Stochastic Top-K Instance Masking (STKIM), which masks out a portion of instances with Top-K attention values and allocates their attention values to the remaining instances. The extensive experimental results on three WSI datasets with two pre-trained backbones reveal that our ACMIL outperforms state-of-the-art methods. Additionally, through heatmap visualization and UMAP visualization, this paper extensively illustrates ACMIL's effectiveness in suppressing attention value concentration and overcoming the overfitting challenge. The source code is available at \url{https://github.com/dazhangyu123/ACMIL}.

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