Zhongyi Shui

Honglin Li, Chenglu Zhu, Yunlong Zhang et al.

While Multiple Instance Learning (MIL) has shown promising results in digital Pathology Whole Slide Image (WSI) classification, such a paradigm still faces performance and generalization problems due to challenges in high computational costs on Gigapixel WSIs and limited sample size for model training. To deal with the computation problem, most MIL methods utilize a frozen pretrained model from ImageNet to obtain representations first. This process may lose essential information owing to the large domain gap and hinder the generalization of model due to the lack of image-level training-time augmentations. Though Self-supervised Learning (SSL) proposes viable representation learning schemes, the improvement of the downstream task still needs to be further explored in the conversion from the task-agnostic features of SSL to the task-specifics under the partial label supervised learning. To alleviate the dilemma of computation cost and performance, we propose an efficient WSI fine-tuning framework motivated by the Information Bottleneck theory. The theory enables the framework to find the minimal sufficient statistics of WSI, thus supporting us to fine-tune the backbone into a task-specific representation only depending on WSI-level weak labels. The WSI-MIL problem is further analyzed to theoretically deduce our fine-tuning method. Our framework is evaluated on five pathology WSI datasets on various WSI heads. The experimental results of our fine-tuned representations show significant improvements in both accuracy and generalization compared with previous works. Source code will be available at https://github.com/invoker-LL/WSI-finetuning.

Zhongyi Shui, Yunlong Zhang, Kai Yao et al.

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}

Zhongyi Shui, Sunyi Zheng, Chenglu Zhu et al.

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 will be available.

Yunlong Zhang, Yuxuan Sun, Sunyi Zheng et al.

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}}

Pingyi Chen, Chenglu Zhu, Zhongyi Shui et al.

The success of supervised deep learning models in medical image segmentation relies on detailed annotations. However, labor-intensive manual labeling is costly and inefficient, especially in dense object segmentation. To this end, we propose a self-supervised learning based approach with a Prior Self-activation Module (PSM) that generates self-activation maps from the input images to avoid labeling costs and further produce pseudo masks for the downstream task. To be specific, we firstly train a neural network using self-supervised learning and utilize the gradient information in the shallow layers of the network to generate self-activation maps. Afterwards, a semantic-guided generator is then introduced as a pipeline to transform visual representations from PSM to pixel-level semantic pseudo masks for downstream tasks. Furthermore, a two-stage training module, consisting of a nuclei detection network and a nuclei segmentation network, is adopted to achieve the final segmentation. Experimental results show the effectiveness on two public pathological datasets. Compared with other fully-supervised and weakly-supervised methods, our method can achieve competitive performance without any manual annotations.

Zhongyi Shui, Yizhi Zhao, Sunyi Zheng et al.

Cell recognition is a fundamental task in digital histopathology image analysis. Point-based cell recognition (PCR) methods normally require a vast number of annotations, which is extremely costly, time-consuming and labor-intensive. Semi-supervised learning (SSL) can provide a shortcut to make full use of cell information in gigapixel whole slide images without exhaustive labeling. However, research into semi-supervised point-based cell recognition (SSPCR) remains largely overlooked. Previous SSPCR works are all built on density map-based PCR models, which suffer from unsatisfactory accuracy, slow inference speed and high sensitivity to hyper-parameters. To address these issues, end-to-end PCR models are proposed recently. In this paper, we develop a SSPCR framework suitable for the end-to-end PCR models for the first time. Overall, we use the current models to generate pseudo labels for unlabeled images, which are in turn utilized to supervise the models training. Besides, we introduce a co-teaching strategy to overcome the confirmation bias problem that generally exists in self-training. A distribution alignment technique is also incorporated to produce high-quality, unbiased pseudo labels for unlabeled data. Experimental results on four histopathology datasets concerning different types of staining styles show the effectiveness and versatility of the proposed framework. Code is available at \textcolor{magenta}{\url{https://github.com/windygooo/SSPCR}

Jingxiong Li, Sunyi Zheng, Zhongyi Shui et al.

Karyotyping is of importance for detecting chromosomal aberrations in human disease. However, chromosomes easily appear curved in microscopic images, which prevents cytogeneticists from analyzing chromosome types. To address this issue, we propose a framework for chromosome straightening, which comprises a preliminary processing algorithm and a generative model called masked conditional variational autoencoders (MC-VAE). The processing method utilizes patch rearrangement to address the difficulty in erasing low degrees of curvature, providing reasonable preliminary results for the MC-VAE. The MC-VAE further straightens the results by leveraging chromosome patches conditioned on their curvatures to learn the mapping between banding patterns and conditions. During model training, we apply a masking strategy with a high masking ratio to train the MC-VAE with eliminated redundancy. This yields a non-trivial reconstruction task, allowing the model to effectively preserve chromosome banding patterns and structure details in the reconstructed results. Extensive experiments on three public datasets with two stain styles show that our framework surpasses the performance of state-of-the-art methods in retaining banding patterns and structure details. Compared to using real-world bent chromosomes, the use of high-quality straightened chromosomes generated by our proposed method can improve the performance of various deep learning models for chromosome classification by a large margin. Such a straightening approach has the potential to be combined with other karyotyping systems to assist cytogeneticists in chromosome analysis.

Pingyi Chen, Honglin Li, Chenglu Zhu et al.

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.

Zhongyi Shui, Shichuan Zhang, Chenglu Zhu et al.

Reliable quantitative analysis of immunohistochemical staining images requires accurate and robust cell detection and classification. Recent weakly-supervised methods usually estimate probability density maps for cell recognition. However, in dense cell scenarios, their performance can be limited by pre- and post-processing as it is impossible to find a universal parameter setting. In this paper, we introduce an end-to-end framework that applies direct regression and classification for preset anchor points. Specifically, we propose a pyramidal feature aggregation strategy to combine low-level features and high-level semantics simultaneously, which provides accurate cell recognition for our purely point-based model. In addition, an optimized cost function is designed to adapt our multi-task learning framework by matching ground truth and predicted points. The experimental results demonstrate the superior accuracy and efficiency of the proposed method, which reveals the high potentiality in assisting pathologist assessments.

Pingyi Chen, Chenglu Zhu, Zhongyi Shui et al.

The success of supervised deep learning models on cell recognition tasks relies on detailed annotations. Many previous works have managed to reduce the dependency on labels. However, considering the large number of cells contained in a patch, costly and inefficient labeling is still inevitable. To this end, we explored label-free methods for cell recognition. Prior self-activation maps (PSM) are proposed to generate pseudo masks as training targets. To be specific, an activation network is trained with self-supervised learning. The gradient information in the shallow layers of the network is aggregated to generate prior self-activation maps. Afterward, a semantic clustering module is then introduced as a pipeline to transform PSMs to pixel-level semantic pseudo masks for downstream tasks. We evaluated our method on two histological datasets: MoNuSeg (cell segmentation) and BCData (multi-class cell detection). Compared with other fully-supervised and weakly-supervised methods, our method can achieve competitive performance without any manual annotations. Our simple but effective framework can also achieve multi-class cell detection which can not be done by existing unsupervised methods. The results show the potential of PSMs that might inspire other research to deal with the hunger for labels in medical area.

Honglin Li, Yusuan Sun, Chenglu Zhu et al.

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.

Sunyi Zheng, Jingxiong Li, Zhongyi Shui et al.

Karyotyping is an important procedure to assess the possible existence of chromosomal abnormalities. However, because of the non-rigid nature, chromosomes are usually heavily curved in microscopic images and such deformed shapes hinder the chromosome analysis for cytogeneticists. In this paper, we present a self-attention guided framework to erase the curvature of chromosomes. The proposed framework extracts spatial information and local textures to preserve banding patterns in a regression module. With complementary information from the bent chromosome, a refinement module is designed to further improve fine details. In addition, we propose two dedicated geometric constraints to maintain the length and restore the distortion of chromosomes. To train our framework, we create a synthetic dataset where curved chromosomes are generated from the real-world straight chromosomes by grid-deformation. Quantitative and qualitative experiments are conducted on synthetic and real-world data. Experimental results show that our proposed method can effectively straighten bent chromosomes while keeping banding details and length.

Honglin Li, Yunlong Zhang, Pingyi Chen et al.

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.

Weiwei Cao, Jianpeng Zhang, Zhongyi Shui et al.

Vision-language pre-training (VLP) has great potential for developing multifunctional and general medical diagnostic capabilities. However, aligning medical images with a low signal-to-noise ratio (SNR) to reports with a high SNR presents a semantic density gap, leading to visual alignment bias. In this paper, we propose boosting vision semantic density to improve alignment effectiveness. On one hand, we enhance visual semantics through disease-level vision contrastive learning, which strengthens the model's ability to differentiate between normal and abnormal samples for each anatomical structure. On the other hand, we introduce an anatomical normality modeling method to model the distribution of normal samples for each anatomy, leveraging VQ-VAE for reconstructing normal vision embeddings in the latent space. This process amplifies abnormal signals by leveraging distribution shifts in abnormal samples, enhancing the model's perception and discrimination of abnormal attributes. The enhanced visual representation effectively captures the diagnostic-relevant semantics, facilitating more efficient and accurate alignment with the diagnostic report. We conduct extensive experiments on two chest CT datasets, CT-RATE and Rad-ChestCT, and an abdominal CT dataset, MedVL-CT69K, and comprehensively evaluate the diagnosis performance across multiple tasks in the chest and abdominal CT scenarios, achieving state-of-the-art zero-shot performance. Notably, our method achieved an average AUC of 84.9% across 54 diseases in 15 organs, significantly surpassing existing methods. Additionally, we demonstrate the superior transfer learning capabilities of our pre-trained model. Code is available at https://github.com/alibaba-damo-academy/ViSD-Boost.

Zhongyi Shui, Ruizhe Guo, Honglin Li et al.

Nucleus detection in histopathology whole slide images (WSIs) is crucial for a broad spectrum of clinical applications. Current approaches for nucleus detection in gigapixel WSIs utilize a sliding window methodology, which overlooks boarder contextual information (eg, tissue structure) and easily leads to inaccurate predictions. To address this problem, recent studies additionally crops a large Filed-of-View (FoV) region around each sliding window to extract contextual features. However, such methods substantially increases the inference latency. In this paper, we propose an effective and efficient context-aware nucleus detection algorithm. Specifically, instead of leveraging large FoV regions, we aggregate contextual clues from off-the-shelf features of historically visited sliding windows. This design greatly reduces computational overhead. Moreover, compared to large FoV regions at a low magnification, the sliding window patches have higher magnification and provide finer-grained tissue details, thereby enhancing the detection accuracy. To further improve the efficiency, we propose a grid pooling technique to compress dense feature maps of each patch into a few contextual tokens. Finally, we craft OCELOT-seg, the first benchmark dedicated to context-aware nucleus instance segmentation. Code, dataset, and model checkpoints will be available at https://github.com/windygoo/PathContext.

Yunlong Zhang, Honglin Li, Yunxuan Sun et al.

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.

Zhongyi Shui, Jianpeng Zhang, Weiwei Cao et al.

Artificial intelligence (AI) shows great potential in assisting radiologists to improve the efficiency and accuracy of medical image interpretation and diagnosis. However, a versatile AI model requires large-scale data and comprehensive annotations, which are often impractical in medical settings. Recent studies leverage radiology reports as a naturally high-quality supervision for medical images, using contrastive language-image pre-training (CLIP) to develop language-informed models for radiological image interpretation. Nonetheless, these approaches typically contrast entire images with reports, neglecting the local associations between imaging regions and report sentences, which may undermine model performance and interoperability. In this paper, we propose a fine-grained vision-language model (fVLM) for anatomy-level CT image interpretation. Specifically, we explicitly match anatomical regions of CT images with corresponding descriptions in radiology reports and perform contrastive pre-training for each anatomy individually. Fine-grained alignment, however, faces considerable false-negative challenges, mainly from the abundance of anatomy-level healthy samples and similarly diseased abnormalities. To tackle this issue, we propose identifying false negatives of both normal and abnormal samples and calibrating contrastive learning from patient-level to disease-aware pairing. We curated the largest CT dataset to date, comprising imaging and report data from 69,086 patients, and conducted a comprehensive evaluation of 54 major and important disease diagnosis tasks across 15 main anatomies. Experimental results demonstrate the substantial potential of fVLM in versatile medical image interpretation. In the zero-shot classification task, we achieved an average AUC of 81.3% on 54 diagnosis tasks, surpassing CLIP and supervised methods by 12.9% and 8.0%, respectively.

Yuxuan Sun, Yixuan Si, Chenglu Zhu et al.

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.

Shichuan Zhang, Sunyi Zheng, Zhongyi Shui et al.

Multi-modal Learning has attracted widespread attention in medical image analysis. Using multi-modal data, whole slide images (WSIs) and clinical information, can improve the performance of deep learning models in the diagnosis of axillary lymph node metastasis. However, clinical information is not easy to collect in clinical practice due to privacy concerns, limited resources, lack of interoperability, etc. Although patient selection can ensure the training set to have multi-modal data for model development, missing modality of clinical information can appear during test. This normally leads to performance degradation, which limits the use of multi-modal models in the clinic. To alleviate this problem, we propose a bidirectional distillation framework consisting of a multi-modal branch and a single-modal branch. The single-modal branch acquires the complete multi-modal knowledge from the multi-modal branch, while the multi-modal learns the robust features of WSI from the single-modal. We conduct experiments on a public dataset of Lymph Node Metastasis in Early Breast Cancer to validate the method. Our approach not only achieves state-of-the-art performance with an AUC of 0.861 on the test set without missing data, but also yields an AUC of 0.842 when the rate of missing modality is 80\%. This shows the effectiveness of the approach in dealing with multi-modal data and missing modality. Such a model has the potential to improve treatment decision-making for early breast cancer patients who have axillary lymph node metastatic status.

Zhongyi Shui, Honglin Li, Xiaozhong Ji et al.

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.

Honglin Li, Zhongyi Shui, Yunlong Zhang et al.

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.

Yuxuan Sun, Yunlong Zhang, Yixuan Si et al.

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.

Yuxuan Sun, Chenglu Zhu, Sunyi Zheng et al.

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.