Yunlong Zhang

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.

Yunlong Zhang, Yuxuan Sun, Honglin Li et al.

When designing a diagnostic model for a clinical application, it is crucial to guarantee the robustness of the model with respect to a wide range of image corruptions. Herein, an easy-to-use benchmark is established to evaluate how deep neural networks perform on corrupted pathology images. Specifically, corrupted images are generated by injecting nine types of common corruptions into validation images. Besides, two classification and one ranking metrics are designed to evaluate the prediction and confidence performance under corruption. Evaluated on two resulting benchmark datasets, we find that (1) a variety of deep neural network models suffer from a significant accuracy decrease (double the error on clean images) and the unreliable confidence estimation on corrupted images; (2) A low correlation between the validation and test errors while replacing the validation set with our benchmark can increase the correlation. Our codes are available on https://github.com/superjamessyx/robustness_benchmark.

Yunlong Zhang, Honglin Li, Yuxuan Sun et al.

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}.

Haote Xu, Yunlong Zhang, Liyan Sun et al.

Anomaly Detection (AD) on medical images enables a model to recognize any type of anomaly pattern without lesion-specific supervised learning. Data augmentation based methods construct pseudo-healthy images by "pasting" fake lesions on real healthy ones, and a network is trained to predict healthy images in a supervised manner. The lesion can be found by difference between the unhealthy input and pseudo-healthy output. However, using only manually designed fake lesions fail to approximate to irregular real lesions, hence limiting the model generalization. We assume by exploring the intrinsic data property within images, we can distinguish previously unseen lesions from healthy regions in an unhealthy image. In this study, we propose an Adaptive Fourier Space Compression (AFSC) module to distill healthy feature for AD. The compression of both magnitude and phase in frequency domain addresses the hyper intensity and diverse position of lesions. Experimental results on the BraTS and MS-SEG datasets demonstrate an AFSC baseline is able to produce promising detection results, and an AFSC module can be effectively embedded into existing AD methods.

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}}

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.

Honglin Li, Yunlong Zhang, Chenglu Zhu et al.

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.

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.

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.

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.

Sunyi Zheng, Xiaonan Cui, Yuxuan Sun et al.

Accurate image classification and retrieval are of importance for clinical diagnosis and treatment decision-making. The recent contrastive language-image pretraining (CLIP) model has shown remarkable proficiency in understanding natural images. Drawing inspiration from CLIP, PathCLIP is specifically designed for pathology image analysis, utilizing over 200,000 image and text pairs in training. While the performance the PathCLIP is impressive, its robustness under a wide range of image corruptions remains unknown. Therefore, we conduct an extensive evaluation to analyze the performance of PathCLIP on various corrupted images from the datasets of Osteosarcoma and WSSS4LUAD. In our experiments, we introduce seven corruption types including brightness, contrast, Gaussian blur, resolution, saturation, hue, and markup at four severity levels. Through experiments, we find that PathCLIP is relatively robustness to image corruptions and surpasses OpenAI-CLIP and PLIP in zero-shot classification. Among the seven corruptions, blur and resolution can cause server performance degradation of the PathCLIP. This indicates that ensuring the quality of images is crucial before conducting a clinical test. Additionally, we assess the robustness of PathCLIP in the task of image-image retrieval, revealing that PathCLIP performs less effectively than PLIP on Osteosarcoma but performs better on WSSS4LUAD under diverse corruptions. Overall, PathCLIP presents impressive zero-shot classification and retrieval performance for pathology images, but appropriate care needs to be taken when using it. We hope this study provides a qualitative impression of PathCLIP and helps understand its differences from other CLIP models.

Kexin Tian, Jingrui Mao, Yunlong Zhang et al.

Recent advancements in Vision-Language Models (VLMs) have demonstrated strong potential for autonomous driving tasks. However, their spatial understanding and reasoning-key capabilities for autonomous driving-still exhibit significant limitations. Notably, none of the existing benchmarks systematically evaluate VLMs' spatial reasoning capabilities in driving scenarios. To fill this gap, we propose NuScenes-SpatialQA, the first large-scale ground-truth-based Question-Answer (QA) benchmark specifically designed to evaluate the spatial understanding and reasoning capabilities of VLMs in autonomous driving. Built upon the NuScenes dataset, the benchmark is constructed through an automated 3D scene graph generation pipeline and a QA generation pipeline. The benchmark systematically evaluates VLMs' performance in both spatial understanding and reasoning across multiple dimensions. Using this benchmark, we conduct extensive experiments on diverse VLMs, including both general and spatial-enhanced models, providing the first comprehensive evaluation of their spatial capabilities in autonomous driving. Surprisingly, the experimental results show that the spatial-enhanced VLM outperforms in qualitative QA but does not demonstrate competitiveness in quantitative QA. In general, VLMs still face considerable challenges in spatial understanding and reasoning.

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.

Chenxin Li, Yunlong Zhang, Zhehan Liang et al.

Retinal artery/vein (A/V) classification is a critical technique for diagnosing diabetes and cardiovascular diseases. Although deep learning based methods achieve impressive results in A/V classification, their performances usually degrade severely when being directly applied to another database, due to the domain shift, e.g., caused by the variations in imaging protocols. In this paper, we propose a novel vessel-mixing based consistency regularization framework, for cross-domain learning in retinal A/V classification. Specially, to alleviate the severe bias to source domain, based on the label smooth prior, the model is regularized to give consistent predictions for unlabeled target-domain inputs that are under perturbation. This consistency regularization implicitly introduces a mechanism where the model and the perturbation is opponent to each other, where the model is pushed to be robust enough to cope with the perturbation. Thus, we investigate a more difficult opponent to further inspire the robustness of model, in the scenario of retinal A/V, called vessel-mixing perturbation. Specially, it effectively disturbs the fundus images especially the vessel structures by mixing two images regionally. We conduct extensive experiments on cross-domain A/V classification using four public datasets, which are collected by diverse institutions and imaging devices. The results demonstrate that our method achieves the state-of-the-art cross-domain performance, which is also close to the upper bound obtained by fully supervised learning on target domain.

Yunlong Zhang, Changxing Jing, Huangxing Lin et al.

Domain adaptation (DA) aims to transfer knowledge from a label-rich and related domain (source domain) to a label-scare domain (target domain). Pseudo-labeling has recently been widely explored and used in DA. However, this line of research is still confined to the inaccuracy of pseudo-labels. In this paper, we reveal an interesting observation that the target samples belonging to the classes with larger domain shift are easier to be misclassified compared with the other classes. These classes are called hard class, which deteriorates the performance of DA and restricts the applications of DA. We propose a novel framework, called Hard Class Rectification Pseudo-labeling (HCRPL), to alleviate the hard class problem from two aspects. First, as is difficult to identify the target samples as hard class, we propose a simple yet effective scheme, named Adaptive Prediction Calibration (APC), to calibrate the predictions of the target samples according to the difficulty degree for each class. Second, we further consider that the predictions of target samples belonging to the hard class are vulnerable to perturbations. To prevent these samples to be misclassified easily, we introduce Temporal-Ensembling (TE) and Self-Ensembling (SE) to obtain consistent predictions. The proposed method is evaluated in both unsupervised domain adaptation (UDA) and semi-supervised domain adaptation (SSDA). The experimental results on several real-world cross-domain benchmarks, including ImageCLEF, Office-31 and Office-Home, substantiates the superiority of the proposed method.