A Survey on Domain Generalization for Medical Image Analysis

Medical Image Analysis (MedIA) has emerged as a crucial tool in computer-aided diagnosis systems, particularly with the advancement of deep learning (DL) in recent years. However, well-trained deep models often experience significant performance degradation when deployed in different medical sites, modalities, and sequences, known as a domain shift issue. In light of this, Domain Generalization (DG) for MedIA aims to address the domain shift challenge by generalizing effectively and performing robustly across unknown data distributions. This paper presents the a comprehensive review of substantial developments in this area. First, we provide a formal definition of domain shift and domain generalization in medical field, and discuss several related settings. Subsequently, we summarize the recent methods from three viewpoints: data manipulation level, feature representation level, and model training level, and present some algorithms in detail for each viewpoints. Furthermore, we introduce the commonly used datasets. Finally, we summarize existing literature and present some potential research topics for the future. For this survey, we also created a GitHub project by collecting the supporting resources, at the link: https://github.com/Ziwei-Niu/DG_for_MedIA

Memory-Inspired Temporal Prompt Interaction for Text-Image Classification

In recent years, large-scale pre-trained multimodal models (LMM) generally emerge to integrate the vision and language modalities, achieving considerable success in various natural language processing and computer vision tasks. The growing size of LMMs, however, results in a significant computational cost for fine-tuning these models for downstream tasks. Hence, prompt-based interaction strategy is studied to align modalities more efficiently. In this contex, we propose a novel prompt-based multimodal interaction strategy inspired by human memory strategy, namely Memory-Inspired Temporal Prompt Interaction (MITP). Our proposed method involves in two stages as in human memory strategy: the acquiring stage, and the consolidation and activation stage. We utilize temporal prompts on intermediate layers to imitate the acquiring stage, leverage similarity-based prompt interaction to imitate memory consolidation, and employ prompt generation strategy to imitate memory activation. The main strength of our paper is that we interact the prompt vectors on intermediate layers to leverage sufficient information exchange between modalities, with compressed trainable parameters and memory usage. We achieve competitive results on several datasets with relatively small memory usage and 2.0M of trainable parameters (about 1% of the pre-trained foundation model).

M2ORT: Many-To-One Regression Transformer for Spatial Transcriptomics Prediction from Histopathology Images

The advancement of Spatial Transcriptomics (ST) has facilitated the spatially-aware profiling of gene expressions based on histopathology images. Although ST data offers valuable insights into the micro-environment of tumors, its acquisition cost remains expensive. Therefore, directly predicting the ST expressions from digital pathology images is desired. Current methods usually adopt existing regression backbones for this task, which ignore the inherent multi-scale hierarchical data structure of digital pathology images. To address this limit, we propose M2ORT, a many-to-one regression Transformer that can accommodate the hierarchical structure of the pathology images through a decoupled multi-scale feature extractor. Different from traditional models that are trained with one-to-one image-label pairs, M2ORT accepts multiple pathology images of different magnifications at a time to jointly predict the gene expressions at their corresponding common ST spot, aiming at learning a many-to-one relationship through training. We have tested M2ORT on three public ST datasets and the experimental results show that M2ORT can achieve state-of-the-art performance with fewer parameters and floating-point operations (FLOPs). The code is available at: https://github.com/Dootmaan/M2ORT/.

Rethinking Multiple Instance Learning for Whole Slide Image Classification: A Bag-Level Classifier is a Good Instance-Level Teacher

Multiple Instance Learning (MIL) has demonstrated promise in Whole Slide Image (WSI) classification. However, a major challenge persists due to the high computational cost associated with processing these gigapixel images. Existing methods generally adopt a two-stage approach, comprising a non-learnable feature embedding stage and a classifier training stage. Though it can greatly reduce the memory consumption by using a fixed feature embedder pre-trained on other domains, such scheme also results in a disparity between the two stages, leading to suboptimal classification accuracy. To address this issue, we propose that a bag-level classifier can be a good instance-level teacher. Based on this idea, we design Iteratively Coupled Multiple Instance Learning (ICMIL) to couple the embedder and the bag classifier at a low cost. ICMIL initially fix the patch embedder to train the bag classifier, followed by fixing the bag classifier to fine-tune the patch embedder. The refined embedder can then generate better representations in return, leading to a more accurate classifier for the next iteration. To realize more flexible and more effective embedder fine-tuning, we also introduce a teacher-student framework to efficiently distill the category knowledge in the bag classifier to help the instance-level embedder fine-tuning. Thorough experiments were conducted on four distinct datasets to validate the effectiveness of ICMIL. The experimental results consistently demonstrate that our method significantly improves the performance of existing MIL backbones, achieving state-of-the-art results. The code is available at: https://github.com/Dootmaan/ICMIL/tree/confidence_based

HAP: Structure-Aware Masked Image Modeling for Human-Centric Perception

Model pre-training is essential in human-centric perception. In this paper, we first introduce masked image modeling (MIM) as a pre-training approach for this task. Upon revisiting the MIM training strategy, we reveal that human structure priors offer significant potential. Motivated by this insight, we further incorporate an intuitive human structure prior - human parts - into pre-training. Specifically, we employ this prior to guide the mask sampling process. Image patches, corresponding to human part regions, have high priority to be masked out. This encourages the model to concentrate more on body structure information during pre-training, yielding substantial benefits across a range of human-centric perception tasks. To further capture human characteristics, we propose a structure-invariant alignment loss that enforces different masked views, guided by the human part prior, to be closely aligned for the same image. We term the entire method as HAP. HAP simply uses a plain ViT as the encoder yet establishes new state-of-the-art performance on 11 human-centric benchmarks, and on-par result on one dataset. For example, HAP achieves 78.1% mAP on MSMT17 for person re-identification, 86.54% mA on PA-100K for pedestrian attribute recognition, 78.2% AP on MS COCO for 2D pose estimation, and 56.0 PA-MPJPE on 3DPW for 3D pose and shape estimation.

Tailored Multi-Organ Segmentation with Model Adaptation and Ensemble

Multi-organ segmentation, which identifies and separates different organs in medical images, is a fundamental task in medical image analysis. Recently, the immense success of deep learning motivated its wide adoption in multi-organ segmentation tasks. However, due to expensive labor costs and expertise, the availability of multi-organ annotations is usually limited and hence poses a challenge in obtaining sufficient training data for deep learning-based methods. In this paper, we aim to address this issue by combining off-the-shelf single-organ segmentation models to develop a multi-organ segmentation model on the target dataset, which helps get rid of the dependence on annotated data for multi-organ segmentation. To this end, we propose a novel dual-stage method that consists of a Model Adaptation stage and a Model Ensemble stage. The first stage enhances the generalization of each off-the-shelf segmentation model on the target domain, while the second stage distills and integrates knowledge from multiple adapted single-organ segmentation models. Extensive experiments on four abdomen datasets demonstrate that our proposed method can effectively leverage off-the-shelf single-organ segmentation models to obtain a tailored model for multi-organ segmentation with high accuracy.

Iteratively Coupled Multiple Instance Learning from Instance to Bag Classifier for Whole Slide Image Classification

Whole Slide Image (WSI) classification remains a challenge due to their extremely high resolution and the absence of fine-grained labels. Presently, WSIs are usually classified as a Multiple Instance Learning (MIL) problem when only slide-level labels are available. MIL methods involve a patch embedding process and a bag-level classification process, but they are prohibitively expensive to be trained end-to-end. Therefore, existing methods usually train them separately, or directly skip the training of the embedder. Such schemes hinder the patch embedder's access to slide-level labels, resulting in inconsistencies within the entire MIL pipeline. To overcome this issue, we propose a novel framework called Iteratively Coupled MIL (ICMIL), which bridges the loss back-propagation process from the bag-level classifier to the patch embedder. In ICMIL, we use category information in the bag-level classifier to guide the patch-level fine-tuning of the patch feature extractor. The refined embedder then generates better instance representations for achieving a more accurate bag-level classifier. By coupling the patch embedder and bag classifier at a low cost, our proposed framework enables information exchange between the two processes, benefiting the entire MIL classification model. We tested our framework on two datasets using three different backbones, and our experimental results demonstrate consistent performance improvements over state-of-the-art MIL methods. Code will be made available upon acceptance.

Super-Resolution Based Patch-Free 3D Medical Image Segmentation with Self-Supervised Guidance

High resolution (HR) 3D medical image segmentation plays an important role in clinical diagnoses. However, HR images are difficult to be directly processed by mainstream graphical cards due to limited video memory. Therefore, most existing 3D medical image segmentation methods use patch-based models, which ignores global context information that is useful in accurate segmentation and has low inference efficiency. To address these problems, we propose a super-resolution (SR) guided patch-free 3D medical image segmentation framework that can realize HR segmentation with global information of low-resolution (LR) input. The framework contains two tasks: semantic segmentation (main task) and super resolution (auxiliary task). To balance the information loss with the LR input, we introduce a Self-Supervised Guidance Module (SGM), which employs a selective search method to crop a HR patch from the original image as restoration guidance. Multi-scale convolutional layers are used to mitigate the scale-inconsistency between the HR guidance features and the LR features. Moreover, we propose a Task-Fusion Module (TFM) to exploit the inter connections between segmentation and SR task. This module can also be used for Test Phase Fine-tuning (TPF), leading to a better model generalization ability. When predicting, only the main segmentation task is needed, while other modules can be removed to accelerate the inference. The experiments results on two different datasets show that our framework outperforms current patch-based and patch-free models. Our model also has a four times higher inference speed compared to traditional patch-based methods. Our codes are available at: https://github.com/Dootmaan/PFSeg-Full.

Label-Efficient Domain Generalization via Collaborative Exploration and Generalization

Considerable progress has been made in domain generalization (DG) which aims to learn a generalizable model from multiple well-annotated source domains to unknown target domains. However, it can be prohibitively expensive to obtain sufficient annotation for source datasets in many real scenarios. To escape from the dilemma between domain generalization and annotation costs, in this paper, we introduce a novel task named label-efficient domain generalization (LEDG) to enable model generalization with label-limited source domains. To address this challenging task, we propose a novel framework called Collaborative Exploration and Generalization (CEG) which jointly optimizes active exploration and semi-supervised generalization. Specifically, in active exploration, to explore class and domain discriminability while avoiding information divergence and redundancy, we query the labels of the samples with the highest overall ranking of class uncertainty, domain representativeness, and information diversity. In semi-supervised generalization, we design MixUp-based intra- and inter-domain knowledge augmentation to expand domain knowledge and generalize domain invariance. We unify active exploration and semi-supervised generalization in a collaborative way and promote mutual enhancement between them, boosting model generalization with limited annotation. Extensive experiments show that CEG yields superior generalization performance. In particular, CEG can even use only 5% data annotation budget to achieve competitive results compared to the previous DG methods with fully labeled data on PACS dataset.