Jingxiong Li

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.

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.

Yuxuan Sun, Hao Wu, Chenglu Zhu et al.

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.

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.

Yunxiang Li, Jingxiong Li, Ruilong Dan et al.

Accurate segmentation is a crucial step in medical image analysis and applying supervised machine learning to segment the organs or lesions has been substantiated effective. However, it is costly to perform data annotation that provides ground truth labels for training the supervised algorithms, and the high variance of data that comes from different domains tends to severely degrade system performance over cross-site or cross-modality datasets. To mitigate this problem, a novel unsupervised domain adaptation (UDA) method named dispensed Transformer network (DTNet) is introduced in this paper. Our novel DTNet contains three modules. First, a dispensed residual transformer block is designed, which realizes global attention by dispensed interleaving operation and deals with the excessive computational cost and GPU memory usage of the Transformer. Second, a multi-scale consistency regularization is proposed to alleviate the loss of details in the low-resolution output for better feature alignment. Finally, a feature ranking discriminator is introduced to automatically assign different weights to domain-gap features to lessen the feature distribution distance, reducing the performance shift of two domains. The proposed method is evaluated on large fluorescein angiography (FA) retinal nonperfusion (RNP) cross-site dataset with 676 images and a wide used cross-modality dataset from the MM-WHS challenge. Extensive results demonstrate that our proposed network achieves the best performance in comparison with several state-of-the-art techniques.

Hanxiao Zhang, Jingxiong Li, Mali Shen et al.

Segmentation of brain tumors and their subregions remains a challenging task due to their weak features and deformable shapes. In this paper, three patterns (cross-skip, skip-1 and skip-2) of distributed dense connections (DDCs) are proposed to enhance feature reuse and propagation of CNNs by constructing tunnels between key layers of the network. For better detecting and segmenting brain tumors from multi-modal 3D MR images, CNN-based models embedded with DDCs (DDU-Nets) are trained efficiently from pixel to pixel with a limited number of parameters. Postprocessing is then applied to refine the segmentation results by reducing the false-positive samples. The proposed method is evaluated on the BraTS 2019 dataset with results demonstrating the effectiveness of the DDU-Nets while requiring less computational cost.