Accurate fetal brain tissue segmentation and biometric measurement are essential for monitoring neurodevelopment and detecting abnormalities in utero. The Fetal Tissue Annotation (FeTA) Challenges have established robust multi-center benchmarks for evaluating state-of-the-art segmentation methods. This paper presents the results of the 2024 challenge edition, which introduced three key innovations. First, we introduced a topology-aware metric based on the Euler characteristic difference (ED) to overcome the performance plateau observed with traditional metrics like Dice or Hausdorff distance (HD), as the performance of the best models in segmentation surpassed the inter-rater variability. While the best teams reached similar scores in Dice (0.81-0.82) and HD95 (2.1-2.3 mm), ED provided greater discriminative power: the winning method achieved an ED of 20.9, representing roughly a 50% improvement over the second- and third-ranked teams despite comparable Dice scores. Second, we introduced a new 0.55T low-field MRI test set, which, when paired with high-quality super-resolution reconstruction, achieved the highest segmentation performance across all test cohorts (Dice=0.86, HD95=1.69, ED=6.26). This provides the first quantitative evidence that low-cost, low-field MRI can match or surpass high-field systems in automated fetal brain segmentation. Third, the new biometry estimation task exposed a clear performance gap: although the best model reached a mean average percentage error (MAPE) of 7.72%, most submissions failed to outperform a simple gestational-age-based linear regression model (MAPE=9.56%), and all remained above inter-rater variability with a MAPE of 5.38%. Finally, by analyzing the top-performing models from FeTA 2024 alongside those from previous challenge editions, we identify ensembles of 3D nnU-Net trained on both real and synthetic data with both image- and anatomy-level augmentations as the most effective approaches for fetal brain segmentation. Our quantitative analysis reveals that acquisition site, super-resolution strategy, and image quality are the primary sources of domain shift, informing recommendations to enhance the robustness and generalizability of automated fetal brain analysis methods.

Semi-Supervised Learning (SSL) is important for reducing the annotation cost for medical image segmentation models. State-of-the-art SSL methods such as Mean Teacher, FixMatch and Cross Pseudo Supervision (CPS) are mainly based on consistency regularization or pseudo-label supervision between a reference prediction and a supervised prediction. Despite the effectiveness, they have overlooked the potential noise in the labeled data, and mainly focus on strategies to generate the reference prediction, while ignoring the heterogeneous values of different unlabeled pixels. We argue that effectively mining the rich information contained by the two predictions in the loss function, instead of the specific strategy to obtain a reference prediction, is more essential for SSL, and propose a universal framework MetaSSL based on a spatially heterogeneous loss that assigns different weights to pixels by simultaneously leveraging the uncertainty and consistency information between the reference and supervised predictions. Specifically, we split the predictions on unlabeled data into four regions with decreasing weights in the loss: Unanimous and Confident (UC), Unanimous and Suspicious (US), Discrepant and Confident (DC), and Discrepant and Suspicious (DS), where an adaptive threshold is proposed to distinguish confident predictions from suspicious ones. The heterogeneous loss is also applied to labeled images for robust learning considering the potential annotation noise. Our method is plug-and-play and general to most existing SSL methods. The experimental results showed that it improved the segmentation performance significantly when integrated with existing SSL frameworks on different datasets. Code is available at https://github.com/HiLab-git/MetaSSL.

Weakly-supervised medical image segmentation methods utilizing image-level labels have gained attention for reducing the annotation cost. They typically use Class Activation Maps (CAM) from a classification network but struggle with incomplete activation regions due to low-resolution localization without detailed boundaries. Differently from most of them that only focus on improving the quality of CAMs, we propose a more unified weakly-supervised segmentation framework with image-level supervision. Firstly, an Uncertainty-weighted Multi-resolution Class Activation Map (UM-CAM) is proposed to generate high-quality pixel-level pseudo-labels. Subsequently, a Geodesic distance-based Seed Expansion (GSE) strategy is introduced to rectify ambiguous boundaries in the UM-CAM by leveraging contextual information. To train a final segmentation model from noisy pseudo-labels, we introduce a Random-View Consensus (RVC) training strategy to suppress unreliable pixel/voxels and encourage consistency between random-view predictions. Extensive experiments on 2D fetal brain segmentation and 3D brain tumor segmentation tasks showed that our method significantly outperforms existing weakly-supervised methods. Code is available at: https://github.com/HiLab-git/UM-CAM .

The performance of deep learning models for medical image segmentation is often limited in scenarios where training data or annotations are limited. Self-Supervised Learning (SSL) is an appealing solution for this dilemma due to its feature learning ability from a large amount of unannotated images. Existing SSL methods have focused on pretraining either an encoder for global feature representation or an encoder-decoder structure for image restoration, where the gap between pretext and downstream tasks limits the usefulness of pretrained decoders in downstream segmentation. In this work, we propose a novel SSL strategy named Volume Fusion (VolF) for pretraining 3D segmentation models. It minimizes the gap between pretext and downstream tasks by introducing a pseudo-segmentation pretext task, where two sub-volumes are fused by a discretized block-wise fusion coefficient map. The model takes the fused result as input and predicts the category of fusion coefficient for each voxel, which can be trained with standard supervised segmentation loss functions without manual annotations. Experiments with an abdominal CT dataset for pretraining and both in-domain and out-domain downstream datasets showed that VolF led to large performance gain from training from scratch with faster convergence speed, and outperformed several state-of-the-art SSL methods. In addition, it is general to different network structures, and the learned features have high generalizability to different body parts and modalities.

Test-Time Adaptation (TTA) offers a practical solution for deploying image segmentation models under domain shift without accessing source data or retraining. Among existing TTA strategies, pseudo-label-based methods have shown promising performance. However, they often rely on perturbation-ensemble heuristics (e.g., dropout sampling, test-time augmentation, Gaussian noise), which lack distributional grounding and yield unstable training signals. This can trigger error accumulation and catastrophic forgetting during adaptation. To address this, we propose A3-TTA, a TTA framework that constructs reliable pseudo-labels through anchor-guided supervision. Specifically, we identify well-predicted target domain images using a class compact density metric, under the assumption that confident predictions imply distributional proximity to the source domain. These anchors serve as stable references to guide pseudo-label generation, which is further regularized via semantic consistency and boundary-aware entropy minimization. Additionally, we introduce a self-adaptive exponential moving average strategy to mitigate label noise and stabilize model update during adaptation. Evaluated on both multi-domain medical images (heart structure and prostate segmentation) and natural images, A3-TTA significantly improves average Dice scores by 10.40 to 17.68 percentage points compared to the source model, outperforming several state-of-the-art TTA methods under different segmentation model architectures. A3-TTA also excels in continual TTA, maintaining high performance across sequential target domains with strong anti-forgetting ability. The code will be made publicly available at https://github.com/HiLab-git/A3-TTA.

Domain Adaptation (DA) is important for a segmentation model to deal with domain shift in a new target domain. Due to the privacy concern of medical data and the expensive annotation process, Source-Free Domain Adaptation (SFDA) is appealing without access to source data and labels of target domain images for the adaptation. However, existing SFDA methods have limited performance due to insufficient supervision and unreliable pseudo labels. In this paper, we propose an enhanced Iterative Pseudo Label Correction (IPLC+) SFDA framework guided by Segment Anything Model (SAM) for medical image segmentation. Specifically, with a pre-trained source model and SAM, we propose a Reliable SAM Pseudo-label Generator (RSPG) to obtain high-quality and reliable pseudo labels in the target domain based on multiple prompts randomly sampled from the model's prediction. To provide more efficient constraints during adaptation, we introduce self-training pseudo labels weighted by the uncertainty, and propose regularization using mean curvature minimization based on shape-prior knowledge for smoother segmentation. We also propose an Iterative Correction Learning (ICL) strategy to iteratively refine pseudo labels using SAM with updated prompts and combine supervisions to optimize the model sufficiently. Experiments on two public multi-site datasets for prostate and heart segmentation show that our method effectively outperformed ten state-of-the-art SFDA methods, improved the quality of pseudo labels, and even achieved better results than fully supervised learning in the target domain in some cases.

Segmentation is a critical step in analyzing the developing human fetal brain. There have been vast improvements in automatic segmentation methods in the past several years, and the Fetal Brain Tissue Annotation (FeTA) Challenge 2021 helped to establish an excellent standard of fetal brain segmentation. However, FeTA 2021 was a single center study, limiting real-world clinical applicability and acceptance. The multi-center FeTA Challenge 2022 focused on advancing the generalizability of fetal brain segmentation algorithms for magnetic resonance imaging (MRI). In FeTA 2022, the training dataset contained images and corresponding manually annotated multi-class labels from two imaging centers, and the testing data contained images from these two centers as well as two additional unseen centers. The multi-center data included different MR scanners, imaging parameters, and fetal brain super-resolution algorithms applied. 16 teams participated and 17 algorithms were evaluated. Here, the challenge results are presented, focusing on the generalizability of the submissions. Both in- and out-of-domain, the white matter and ventricles were segmented with the highest accuracy (Top Dice scores: 0.89, 0.87 respectively), while the most challenging structure remains the grey matter (Top Dice score: 0.75) due to anatomical complexity. The top 5 average Dices scores ranged from 0.81-0.82, the top 5 average percentile Hausdorff distance values ranged from 2.3-2.5mm, and the top 5 volumetric similarity scores ranged from 0.90-0.92. The FeTA Challenge 2022 was able to successfully evaluate and advance generalizability of multi-class fetal brain tissue segmentation algorithms for MRI and it continues to benchmark new algorithms.

Classification of pathological images is the basis for automatic cancer diagnosis. Despite that deep learning methods have achieved remarkable performance, they heavily rely on labeled data, demanding extensive human annotation efforts. In this study, we present a novel human annotation-free method by leveraging pre-trained Vision-Language Models (VLMs). Without human annotation, pseudo-labels of the training set are obtained by utilizing the zero-shot inference capabilities of VLM, which may contain a lot of noise due to the domain gap between the pre-training and target datasets. To address this issue, we introduce VLM-CPL, a novel approach that contains two noisy label filtering techniques with a semi-supervised learning strategy. Specifically, we first obtain prompt-based pseudo-labels with uncertainty estimation by zero-shot inference with the VLM using multiple augmented views of an input. Then, by leveraging the feature representation ability of VLM, we obtain feature-based pseudo-labels via sample clustering in the feature space. Prompt-feature consensus is introduced to select reliable samples based on the consensus between the two types of pseudo-labels. We further propose High-confidence Cross Supervision by to learn from samples with reliable pseudo-labels and the remaining unlabeled samples. Additionally, we present an innovative open-set prompting strategy that filters irrelevant patches from whole slides to enhance the quality of selected patches. Experimental results on five public pathological image datasets for patch-level and slide-level classification showed that our method substantially outperformed zero-shot classification by VLMs, and was superior to existing noisy label learning methods. The code is publicly available at https://github.com/HiLab-git/VLM-CPL.

Deep neural networks typically require accurate and a large number of annotations to achieve outstanding performance in medical image segmentation. One-shot and weakly-supervised learning are promising research directions that reduce labeling effort by learning a new class from only one annotated image and using coarse labels instead, respectively. In this work, we present an innovative framework for 3D medical image segmentation with one-shot and weakly-supervised settings. Firstly a propagation-reconstruction network is proposed to propagate scribbles from one annotated volume to unlabeled 3D images based on the assumption that anatomical patterns in different human bodies are similar. Then a multi-level similarity denoising module is designed to refine the scribbles based on embeddings from anatomical- to pixel-level. After expanding the scribbles to pseudo masks, we observe the miss-classified voxels mainly occur at the border region and propose to extract self-support prototypes for the specific refinement. Based on these weakly-supervised segmentation results, we further train a segmentation model for the new class with the noisy label training strategy. Experiments on three CT and one MRI datasets show the proposed method obtains significant improvement over the state-of-the-art methods and performs robustly even under severe class imbalance and low contrast. Code is publicly available at https://github.com/LWHYC/OneShot_WeaklySeg.

Adapting a medical image segmentation model to a new domain is important for improving its cross-domain transferability, and due to the expensive annotation process, Unsupervised Domain Adaptation (UDA) is appealing where only unlabeled images are needed for the adaptation. Existing UDA methods are mainly based on image or feature alignment with adversarial training for regularization, and they are limited by insufficient supervision in the target domain. In this paper, we propose an enhanced Filtered Pseudo Label (FPL+)-based UDA method for 3D medical image segmentation. It first uses cross-domain data augmentation to translate labeled images in the source domain to a dual-domain training set consisting of a pseudo source-domain set and a pseudo target-domain set. To leverage the dual-domain augmented images to train a pseudo label generator, domain-specific batch normalization layers are used to deal with the domain shift while learning the domain-invariant structure features, generating high-quality pseudo labels for target-domain images. We then combine labeled source-domain images and target-domain images with pseudo labels to train a final segmentor, where image-level weighting based on uncertainty estimation and pixel-level weighting based on dual-domain consensus are proposed to mitigate the adverse effect of noisy pseudo labels. Experiments on three public multi-modal datasets for Vestibular Schwannoma, brain tumor and whole heart segmentation show that our method surpassed ten state-of-the-art UDA methods, and it even achieved better results than fully supervised learning in the target domain in some cases.

Accurate segmentation of brain tumors from medical images is important for diagnosis and treatment planning, and it often requires multi-modal or contrast-enhanced images. However, in practice some modalities of a patient may be absent. Synthesizing the missing modality has a potential for filling this gap and achieving high segmentation performance. Existing methods often treat the synthesis and segmentation tasks separately or consider them jointly but without effective regularization of the complex joint model, leading to limited performance. We propose a novel brain Tumor Image Synthesis and Segmentation network (TISS-Net) that obtains the synthesized target modality and segmentation of brain tumors end-to-end with high performance. First, we propose a dual-task-regularized generator that simultaneously obtains a synthesized target modality and a coarse segmentation, which leverages a tumor-aware synthesis loss with perceptibility regularization to minimize the high-level semantic domain gap between synthesized and real target modalities. Based on the synthesized image and the coarse segmentation, we further propose a dual-task segmentor that predicts a refined segmentation and error in the coarse segmentation simultaneously, where a consistency between these two predictions is introduced for regularization. Our TISS-Net was validated with two applications: synthesizing FLAIR images for whole glioma segmentation, and synthesizing contrast-enhanced T1 images for Vestibular Schwannoma segmentation. Experimental results showed that our TISS-Net largely improved the segmentation accuracy compared with direct segmentation from the available modalities, and it outperformed state-of-the-art image synthesis-based segmentation methods.

Domain Adaptation (DA) has recently been of strong interest in the medical imaging community. While a large variety of DA techniques have been proposed for image segmentation, most of these techniques have been validated either on private datasets or on small publicly available datasets. Moreover, these datasets mostly addressed single-class problems. To tackle these limitations, the Cross-Modality Domain Adaptation (crossMoDA) challenge was organised in conjunction with the 24th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2021). CrossMoDA is the first large and multi-class benchmark for unsupervised cross-modality Domain Adaptation. The goal of the challenge is to segment two key brain structures involved in the follow-up and treatment planning of vestibular schwannoma (VS): the VS and the cochleas. Currently, the diagnosis and surveillance in patients with VS are commonly performed using contrast-enhanced T1 (ceT1) MR imaging. However, there is growing interest in using non-contrast imaging sequences such as high-resolution T2 (hrT2) imaging. For this reason, we established an unsupervised cross-modality segmentation benchmark. The training dataset provides annotated ceT1 scans (N=105) and unpaired non-annotated hrT2 scans (N=105). The aim was to automatically perform unilateral VS and bilateral cochlea segmentation on hrT2 scans as provided in the testing set (N=137). This problem is particularly challenging given the large intensity distribution gap across the modalities and the small volume of the structures. A total of 55 teams from 16 countries submitted predictions to the validation leaderboard. Among them, 16 teams from 9 different countries submitted their algorithm for the evaluation phase. The level of performance reached by the top-performing teams is strikingly high (best median Dice score — VS: 88.4%; Cochleas: 85.7%) and close to full supervision (median Dice score — VS: 92.5%; Cochleas: 87.7%). All top-performing methods made use of an image-to-image translation approach to transform the source-domain images into pseudo-target-domain images. A segmentation network was then trained using these generated images and the manual annotations provided for the source image.

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, gray matter, white matter, ventricles, cerebellum, brainstem, deep gray matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero.

Deep-learning-based automatic defect segmentation is one of the hot research areas in computer vision application for the task of intelligent industrial inspection. Recently, several state-of-the-art models for image segmentation task have been proposed. However, their high performance is vastly dependent on the availability of large set of labeled data, which is one of the hindering factors in achieving full potential with deep learning methods in industrial inspection. In this article, we propose a novel method based on pairwise similarity map consistency with ensemble-based cross pseudolabels for semisupervised defect segmentation that uses limited labeled samples while exploiting additional label-free samples. The proposed approach uses three network branches that are regularized by pairwise similarity map consistency, and each of them is supervised by the pseudolabels generated by ensemble of predictions of the other two networks for the unlabeled samples. The proposed method achieved significant performance improvement over the baseline of learning only from the labeled images and the current state-of-the-art semisupervised methods. We perform ablation studies and extensive experiments on various parameters and components to demonstrate that our method achieved state-of-the-art results on three different datasets.

Convolutional Neural Networks (CNNs) have achieved state-of-the-art performance for medical image segmentation, yet need plenty of manual annotations for training. Semi-Supervised Learning (SSL) methods are promising to reduce the requirement of annotations, but their performance is still limited when the dataset size and the number of annotated images are small. Leveraging existing annotated datasets with similar anatomical structures to assist training has a potential for improving the model's performance. However, it is further challenged by the cross-anatomy domain shift due to the image modalities and even different organs in the target domain. To solve this problem, we propose Contrastive Semi-supervised learning for Cross Anatomy Domain Adaptation (CS-CADA) that adapts a model to segment similar structures in a target domain, which requires only limited annotations in the target domain by leveraging a set of existing annotated images of similar structures in a source domain. We use Domain-Specific Batch Normalization (DSBN) to individually normalize feature maps for the two anatomical domains, and propose a cross-domain contrastive learning strategy to encourage extracting domain invariant features. They are integrated into a Self-Ensembling Mean-Teacher (SE-MT) framework to exploit unlabeled target domain images with a prediction consistency constraint. Extensive experiments show that our CS-CADA is able to solve the challenging cross-anatomy domain shift problem, achieving accurate segmentation of coronary arteries in X-ray images with the help of retinal vessel images and cardiac MR images with the help of fundus images, respectively, given only a small number of annotations in the target domain. Our code is available at https://github.com/HiLab-git/DAG4MIA.

Domain Adaptation (DA) is important for deep learning-based medical image segmentation models to deal with testing images from a new target domain. As the source-domain data are usually unavailable when a trained model is deployed at a new center, Source-Free Domain Adaptation (SFDA) is appealing for data and annotation-efficient adaptation to the target domain. However, existing SFDA methods have a limited performance due to lack of sufficient supervision with source-domain images unavailable and target-domain images unlabeled. We propose a novel Uncertainty-aware Pseudo Label guided (UPL) SFDA method for medical image segmentation. Specifically, we propose Target Domain Growing (TDG) to enhance the diversity of predictions in the target domain by duplicating the pre-trained model's prediction head multiple times with perturbations. The different predictions in these duplicated heads are used to obtain pseudo labels for unlabeled target-domain images and their uncertainty to identify reliable pseudo labels. We also propose a Twice Forward pass Supervision (TFS) strategy that uses reliable pseudo labels obtained in one forward pass to supervise predictions in the next forward pass. The adaptation is further regularized by a mean prediction-based entropy minimization term that encourages confident and consistent results in different prediction heads. UPL-SFDA was validated with a multi-site heart MRI segmentation dataset, a cross-modality fetal brain segmentation dataset, and a 3D fetal tissue segmentation dataset. It improved the average Dice by 5.54, 5.01 and 6.89 percentage points for the three tasks compared with the baseline, respectively, and outperformed several state-of-the-art SFDA methods.

The success of Convolutional Neural Networks (CNNs) in 3D medical image segmentation relies on massive fully annotated 3D volumes for training that are time-consuming and labor-intensive to acquire. In this paper, we propose to annotate a segmentation target with only seven points in 3D medical images, and design a two-stage weakly supervised learning framework PA-Seg. In the first stage, we employ geodesic distance transform to expand the seed points to provide more supervision signal. To further deal with unannotated image regions during training, we propose two contextual regularization strategies, i.e., multi-view Conditional Random Field (mCRF) loss and Variance Minimization (VM) loss, where the first one encourages pixels with similar features to have consistent labels, and the second one minimizes the intensity variance for the segmented foreground and background, respectively. In the second stage, we use predictions obtained by the model pre-trained in the first stage as pseudo labels. To overcome noises in the pseudo labels, we introduce a Self and Cross Monitoring (SCM) strategy, which combines self-training with Cross Knowledge Distillation (CKD) between a primary model and an auxiliary model that learn from soft labels generated by each other. Experiments on public datasets for Vestibular Schwannoma (VS) segmentation and Brain Tumor Segmentation (BraTS) demonstrated that our model trained in the first stage outperformed existing state-of-the-art weakly supervised approaches by a large margin, and after using SCM for additional training, the model's performance was close to its fully supervised counterpart on the BraTS dataset.

In clinical practice, it is desirable for medical image segmentation models to be able to continually learn on a sequential data stream from multiple sites, rather than a consolidated dataset, due to storage cost and privacy restrictions. However, when learning on a new site, existing methods struggle with a weak memorizability for previous sites with complex shape and semantic information, and a poor explainability for the memory consolidation process. In this work, we propose a novel Shape and Semantics-based Selective Regularization ( [Formula: see text]) method for explainable cross-site continual segmentation to maintain both shape and semantic knowledge of previously learned sites. Specifically, [Formula: see text] method adopts a selective regularization scheme to penalize changes of parameters with high Joint Shape and Semantics-based Importance (JSSI) weights, which are estimated based on the parameter sensitivity to shape properties and reliable semantics of the segmentation object. This helps to prevent the related shape and semantic knowledge from being forgotten. Moreover, we propose an Importance Activation Mapping (IAM) method for memory interpretation, which indicates the spatial support for important parameters to visualize the memorized content. We have extensively evaluated our method on prostate segmentation and optic cup and disc segmentation tasks. Our method outperforms other comparison methods in reducing model forgetting and increasing explainability. Our code is available at https://github.com/jingyzhang/S3R.

Accurate segmentation of multiple abdominal organs from Computed Tomography (CT) images plays an important role in computer-aided diagnosis, treatment planning and follow-up. Currently, 3D Convolution Neural Networks (CNN) have achieved promising performance for automatic medical image segmentation tasks. However, most existing 3D CNNs have a large set of parameters and huge floating point operations (FLOPs), and 3D CT volumes have a large size, leading to high computational cost, which limits their clinical application. To tackle this issue, we propose a novel framework based on lightweight network and Knowledge Distillation (KD) for delineating multiple organs from 3D CT volumes. We first propose a novel lightweight medical image segmentation network named LCOV-Net for reducing the model size and then introduce two knowledge distillation modules (i.e., Class-Affinity KD and Multi-Scale KD) to effectively distill the knowledge from a heavy-weight teacher model to improve LCOV-Net's segmentation accuracy. Experiments on two public abdominal CT datasets for multiple organ segmentation showed that: 1) Our LCOV-Net outperformed existing lightweight 3D segmentation models in both computational cost and accuracy; 2) The proposed KD strategy effectively improved the performance of the lightweight network, and it outperformed existing KD methods; 3) Combining the proposed LCOV-Net and KD strategy, our framework achieved better performance than the state-of-the-art 3D nnU-Net with only one-fifth parameters. The code is available at https://github.com/HiLab-git/LCOVNet-and-KD.

Semantic segmentation of histopathological images is important for automatic cancer diagnosis, and it is challenged by time-consuming and labor-intensive annotation process that obtains pixel-level labels for training. To reduce annotation costs, Weakly Supervised Semantic Segmentation (WSSS) aims to segment objects by only using image or patch-level classification labels. Current WSSS methods are mostly based on Class Activation Map (CAM) that usually locates the most discriminative object part with limited segmentation accuracy. In this work, we propose a novel two-stage weakly supervised segmentation framework based on High-resolution Activation Maps and Interleaved Learning (HAMIL). First, we propose a simple yet effective Classification Network with High-resolution Activation Maps (HAM-Net) that exploits a lightweight classification head combined with Multiple Layer Fusion (MLF) of activation maps and Monte Carlo Augmentation (MCA) to obtain precise foreground regions. Second, we use dense pseudo labels generated by HAM-Net to train a better segmentation model, where three networks with the same structure are trained with interleaved learning: The agreement between two networks is used to highlight reliable pseudo labels for training the third network, and at the same time, the two networks serve as teachers for guiding the third network via knowledge distillation. Extensive experiments on two public histopathological image datasets of lung cancer demonstrated that our proposed HAMIL outperformed state-of-the-art weakly supervised and noisy label learning methods, respectively. The code is available at https://github.com/HiLab-git/HAMIL.

The computer-assisted rehabilitation environment (CAREN) system plays an important role in the training of rehabilitation patients, where the capture of the patient's 3-D pose and gait is critical for assessing the patient's requirements for effective training. Vision-based methods are highly effective for this task due to their low cost, high speed, and noninterference. Although various general vision-based pose estimation methods were developed recently, their performance is limited in the CAREN system due to the specific environment. To address these problems, we propose an improved framework for accurate 2-D and 3-D pose estimation for the CAREN system through using multiview videos. First, for 2-D pose estimation, we propose a coarse-to-fine heatmap shrinking (CFHS) strategy that gradually reduces the kernel size of the heatmap of joints during training to improve the performance. Second, to further obtain 3-D pose estimations, we propose a novel spatial-temporal perception network that fuses the 2-D results from multiple views and multiple moments; multiview early fusion uses complementary spatial information from different views, and multimoment late fusion leverages temporal information from the sequential input for higher accuracy. The experimental results, based on CAREN videos of 225 orthopedic patients, showed that the accuracy of 2-D human pose estimations with the CFHS training strategy reached 99.85% [email protected]. For 3-D results, the mean per joint position error was 25.22 mm, and the 3DPCK reached 98.71%, which outperformed existing general video-based methods. The results showed that the proposed system is capable of estimating human poses with high accuracy for clinical applications.

Accurate segmentation of Anatomical brain Barriers to Cancer spread (ABCs) plays an important role for automatic delineation of Clinical Target Volume (CTV) of brain tumors in radiotherapy. Despite that variants of U-Net are state-of-the-art segmentation models, they have limited performance when dealing with ABCs structures with various shapes and sizes, especially thin structures (e.g., the falx cerebri) that span only few slices. To deal with this problem, we propose a High and Multi-Resolution Network (HMRNet) that consists of a multi-scale feature learning branch and a high-resolution branch, which can maintain the high-resolution contextual information and extract more robust representations of anatomical structures with various scales. We further design a Bidirectional Feature Calibration (BFC) block to enable the two branches to generate spatial attention maps for mutual feature calibration. Considering the different sizes and positions of ABCs structures, our network was applied after a rough localization of each structure to obtain fine segmentation results. Experiments on the MICCAI 2020 ABCs challenge dataset showed that: 1) Our proposed two-stage segmentation strategy largely outperformed methods segmenting all the structures in just one stage; 2) The proposed HMRNet with two branches can maintain high-resolution representations and is effective to improve the performance on thin structures; 3) The proposed BFC block outperformed existing attention methods using monodirectional feature calibration. Our method won the second place of ABCs 2020 challenge and has a potential for more accurate and reasonable delineation of CTV of brain tumors.

Automatic segmentation of COVID-19 pneumonia lesions is critical for quantitative measurement for diagnosis and treatment management. For this task, deep learning is the state-of-the-art method while requires a large set of accurately annotated images for training, which is difficult to obtain due to limited access to experts and the time-consuming annotation process. To address this problem, we aim to train the segmentation network from imperfect annotations, where the training set consists of a small clean set of accurately annotated images by experts and a large noisy set of inaccurate annotations by non-experts. To avoid the labels with different qualities corrupting the segmentation model, we propose a new approach to train segmentation networks to deal with noisy labels. We introduce a dual-branch network to separately learn from the accurate and noisy annotations. To fully exploit the imperfect annotations as well as suppressing the noise, we design a Divergence-Aware Selective Training (DAST) strategy, where a divergence-aware noisiness score is used to identify severely noisy annotations and slightly noisy annotations. For severely noisy samples we use an regularization through dual-branch consistency between predictions from the two branches. We also refine slightly noisy samples and use them as supplementary data for the clean branch to avoid overfitting. Experimental results show that our method achieves a higher performance than standard training process for COVID-19 pneumonia lesion segmentation when learning from imperfect labels, and our framework outperforms the state-of-the-art noise-tolerate methods significantly with various clean label percentages.

Computed Tomography (CT) plays an important role in monitoring radiation-induced Pulmonary Fibrosis (PF), where accurate segmentation of the PF lesions is highly desired for diagnosis and treatment follow-up. However, the task is challenged by ambiguous boundary, irregular shape, various position and size of the lesions, as well as the difficulty in acquiring a large set of annotated volumetric images for training. To overcome these problems, we propose a novel convolutional neural network called PF-Net and incorporate it into a semi-supervised learning framework based on Iterative Confidence-based Refinement And Weighting of pseudo Labels (I-CRAWL). Our PF-Net combines 2D and 3D convolutions to deal with CT volumes with large inter-slice spacing, and uses multi-scale guided dense attention to segment complex PF lesions. For semi-supervised learning, our I-CRAWL employs pixel-level uncertainty-based confidence-aware refinement to improve the accuracy of pseudo labels of unannotated images, and uses image-level uncertainty for confidence-based image weighting to suppress low-quality pseudo labels in an iterative training process. Extensive experiments with CT scans of Rhesus Macaques with radiation-induced PF showed that: 1) PF-Net achieved higher segmentation accuracy than existing 2D, 3D and 2.5D neural networks, and 2) I-CRAWL outperformed state-of-the-art semi-supervised learning methods for the PF lesion segmentation task. Our method has a potential to improve the diagnosis of PF and clinical assessment of side effects of radiotherapy for lung cancers.

Deep learning-based semi-supervised learning (SSL) algorithms have led to promising results in medical images segmentation and can alleviate doctors' expensive annotations by leveraging unlabeled data. However, most of the existing SSL algorithms in literature tend to regularize the model training by perturbing networks and/or data. Observing that multi/dual-task learning attends to various levels of information which have inherent prediction perturbation, we ask the question in this work: can we explicitly build task-level regularization rather than implicitly constructing networks- and/or data-level perturbation and then regularization for SSL? To answer this question, we propose a novel dual-task-consistency semi-supervised framework for the first time. Concretely, we use a dual-task deep network that jointly predicts a pixel-wise segmentation map and a geometry-aware level set representation of the target. The level set representation is converted to an approximated segmentation map through a differentiable task transform layer. Simultaneously, we introduce a dual-task consistency regularization between the level set-derived segmentation maps and directly predicted segmentation maps for both labeled and unlabeled data. Extensive experiments on two public datasets show that our method can largely improve the performance by incorporating the unlabeled data. Meanwhile, our framework outperforms the state-of-the-art semi-supervised learning methods.

Intraoperative tracking of laparoscopic instruments is often a prerequisite for computer and robotic-assisted interventions. While numerous methods for detecting, segmenting and tracking of medical instruments based on endoscopic video images have been proposed in the literature, key limitations remain to be addressed: Firstly, robustness, that is, the reliable performance of state-of-the-art methods when run on challenging images (e.g. in the presence of blood, smoke or motion artifacts). Secondly, generalization; algorithms trained for a specific intervention in a specific hospital should generalize to other interventions or institutions. In an effort to promote solutions for these limitations, we organized the Robust Medical Instrument Segmentation (ROBUST-MIS) challenge as an international benchmarking competition with a specific focus on the robustness and generalization capabilities of algorithms. For the first time in the field of endoscopic image processing, our challenge included a task on binary segmentation and also addressed multi-instance detection and segmentation. The challenge was based on a surgical data set comprising 10,040 annotated images acquired from a total of 30 surgical procedures from three different types of surgery. The validation of the competing methods for the three tasks (binary segmentation, multi-instance detection and multi-instance segmentation) was performed in three different stages with an increasing domain gap between the training and the test data. The results confirm the initial hypothesis, namely that algorithm performance degrades with an increasing domain gap. While the average detection and segmentation quality of the best-performing algorithms is high, future research should concentrate on detection and segmentation of small, crossing, moving and transparent instrument(s) (parts).

Accurate medical image segmentation is essential for diagnosis and treatment planning of diseases. Convolutional Neural Networks (CNNs) have achieved state-of-the-art performance for automatic medical image segmentation. However, they are still challenged by complicated conditions where the segmentation target has large variations of position, shape and scale, and existing CNNs have a poor explainability that limits their application to clinical decisions. In this work, we make extensive use of multiple attentions in a CNN architecture and propose a comprehensive attention-based CNN (CA-Net) for more accurate and explainable medical image segmentation that is aware of the most important spatial positions, channels and scales at the same time. In particular, we first propose a joint spatial attention module to make the network focus more on the foreground region. Then, a novel channel attention module is proposed to adaptively recalibrate channel-wise feature responses and highlight the most relevant feature channels. Also, we propose a scale attention module implicitly emphasizing the most salient feature maps among multiple scales so that the CNN is adaptive to the size of an object. Extensive experiments on skin lesion segmentation from ISIC 2018 and multi-class segmentation of fetal MRI found that our proposed CA-Net significantly improved the average segmentation Dice score from 87.77% to 92.08% for skin lesion, 84.79% to 87.08% for the placenta and 93.20% to 95.88% for the fetal brain respectively compared with U-Net. It reduced the model size to around 15 times smaller with close or even better accuracy compared with state-of-the-art DeepLabv3+. In addition, it has a much higher explainability than existing networks by visualizing the attention weight maps. Our code is available at https://github.com/HiLab-git/CA-Net.

Despite that deep learning has achieved state-of-the-art performance for medical image segmentation, its success relies on a large set of manually annotated images for training that are expensive to acquire. In this paper, we propose an annotation-efficient learning framework for segmentation tasks that avoids annotations of training images, where we use an improved Cycle-Consistent Generative Adversarial Network (GAN) to learn from a set of unpaired medical images and auxiliary masks obtained either from a shape model or public datasets. We first use the GAN to generate pseudo labels for our training images under the implicit high-level shape constraint represented by a Variational Auto-encoder (VAE)-based discriminator with the help of the auxiliary masks, and build a Discriminator-guided Generator Channel Calibration (DGCC) module which employs our discriminator's feedback to calibrate the generator for better pseudo labels. To learn from the pseudo labels that are noisy, we further introduce a noise-robust iterative learning method using noise-weighted Dice loss. We validated our framework with two situations: objects with a simple shape model like optic disc in fundus images and fetal head in ultrasound images, and complex structures like lung in X-Ray images and liver in CT images. Experimental results demonstrated that 1) Our VAE-based discriminator and DGCC module help to obtain high-quality pseudo labels. 2) Our proposed noise-robust learning method can effectively overcome the effect of noisy pseudo labels. 3) The segmentation performance of our method without using annotations of training images is close or even comparable to that of learning from human annotations.

Segmentation of pneumonia lesions from CT scans of COVID-19 patients is important for accurate diagnosis and follow-up. Deep learning has a potential to automate this task but requires a large set of high-quality annotations that are difficult to collect. Learning from noisy training labels that are easier to obtain has a potential to alleviate this problem. To this end, we propose a novel noise-robust framework to learn from noisy labels for the segmentation task. We first introduce a noise-robust Dice loss that is a generalization of Dice loss for segmentation and Mean Absolute Error (MAE) loss for robustness against noise, then propose a novel COVID-19 Pneumonia Lesion segmentation network (COPLE-Net) to better deal with the lesions with various scales and appearances. The noise-robust Dice loss and COPLE-Net are combined with an adaptive self-ensembling framework for training, where an Exponential Moving Average (EMA) of a student model is used as a teacher model that is adaptively updated by suppressing the contribution of the student to EMA when the student has a large training loss. The student model is also adaptive by learning from the teacher only when the teacher outperforms the student. Experimental results showed that: (1) our noise-robust Dice loss outperforms existing noise-robust loss functions, (2) the proposed COPLE-Net achieves higher performance than state-of-the-art image segmentation networks, and (3) our framework with adaptive self-ensembling significantly outperforms a standard training process and surpasses other noise-robust training approaches in the scenario of learning from noisy labels for COVID-19 pneumonia lesion segmentation.

Despite the state-of-the-art performance for medical image segmentation, deep convolutional neural networks (CNNs) have rarely provided uncertainty estimations regarding their segmentation outputs, e.g., model (epistemic) and image-based (aleatoric) uncertainties. In this work, we analyze these different types of uncertainties for CNN-based 2D and 3D medical image segmentation tasks at both pixel level and structure level. We additionally propose a test-time augmentation-based aleatoric uncertainty to analyze the effect of different transformations of the input image on the segmentation output. Test-time augmentation has been previously used to improve segmentation accuracy, yet not been formulated in a consistent mathematical framework. Hence, we also propose a theoretical formulation of test-time augmentation, where a distribution of the prediction is estimated by Monte Carlo simulation with prior distributions of parameters in an image acquisition model that involves image transformations and noise. We compare and combine our proposed aleatoric uncertainty with model uncertainty. Experiments with segmentation of fetal brains and brain tumors from 2D and 3D Magnetic Resonance Images (MRI) showed that 1) the test-time augmentation-based aleatoric uncertainty provides a better uncertainty estimation than calculating the test-time dropout-based model uncertainty alone and helps to reduce overconfident incorrect predictions, and 2) our test-time augmentation outperforms a single-prediction baseline and dropout-based multiple predictions.

Accurate medical image segmentation is essential for diagnosis, surgical planning and many other applications. Convolutional Neural Networks (CNNs) have become the state-of-the-art automatic segmentation methods. However, fully automatic results may still need to be refined to become accurate and robust enough for clinical use. We propose a deep learning-based interactive segmentation method to improve the results obtained by an automatic CNN and to reduce user interactions during refinement for higher accuracy. We use one CNN to obtain an initial automatic segmentation, on which user interactions are added to indicate mis-segmentations. Another CNN takes as input the user interactions with the initial segmentation and gives a refined result. We propose to combine user interactions with CNNs through geodesic distance transforms, and propose a resolution-preserving network that gives a better dense prediction. In addition, we integrate user interactions as hard constraints into a back-propagatable Conditional Random Field. We validated the proposed framework in the context of 2D placenta segmentation from fetal MRI and 3D brain tumor segmentation from FLAIR images. Experimental results show our method achieves a large improvement from automatic CNNs, and obtains comparable and even higher accuracy with fewer user interventions and less time compared with traditional interactive methods.

One of the fundamental challenges in supervised learning for multimodal image registration is the lack of ground-truth for voxel-level spatial correspondence. This work describes a method to infer voxel-level transformation from higher-level correspondence information contained in anatomical labels. We argue that such labels are more reliable and practical to obtain for reference sets of image pairs than voxel-level correspondence. Typical anatomical labels of interest may include solid organs, vessels, ducts, structure boundaries and other subject-specific ad hoc landmarks. The proposed end-to-end convolutional neural network approach aims to predict displacement fields to align multiple labelled corresponding structures for individual image pairs during the training, while only unlabelled image pairs are used as the network input for inference. We highlight the versatility of the proposed strategy, for training, utilising diverse types of anatomical labels, which need not to be identifiable over all training image pairs. At inference, the resulting 3D deformable image registration algorithm runs in real-time and is fully-automated without requiring any anatomical labels or initialisation. Several network architecture variants are compared for registering T2-weighted magnetic resonance images and 3D transrectal ultrasound images from prostate cancer patients. A median target registration error of 3.6 mm on landmark centroids and a median Dice of 0.87 on prostate glands are achieved from cross-validation experiments, in which 108 pairs of multimodal images from 76 patients were tested with high-quality anatomical labels.

Convolutional neural networks (CNNs) have achieved state-of-the-art performance for automatic medical image segmentation. However, they have not demonstrated sufficiently accurate and robust results for clinical use. In addition, they are limited by the lack of image-specific adaptation and the lack of generalizability to previously unseen object classes (a.k.a. zero-shot learning). To address these problems, we propose a novel deep learning-based interactive segmentation framework by incorporating CNNs into a bounding box and scribble-based segmentation pipeline. We propose image-specific fine tuning to make a CNN model adaptive to a specific test image, which can be either unsupervised (without additional user interactions) or supervised (with additional scribbles). We also propose a weighted loss function considering network and interaction-based uncertainty for the fine tuning. We applied this framework to two applications: 2-D segmentation of multiple organs from fetal magnetic resonance (MR) slices, where only two types of these organs were annotated for training and 3-D segmentation of brain tumor core (excluding edema) and whole brain tumor (including edema) from different MR sequences, where only the tumor core in one MR sequence was annotated for training. Experimental results show that: 1) our model is more robust to segment previously unseen objects than state-of-the-art CNNs; 2) image-specific fine tuning with the proposed weighted loss function significantly improves segmentation accuracy; and 3) our method leads to accurate results with fewer user interactions and less user time than traditional interactive segmentation methods.

Segmentation of the placenta from fetal MRI is challenging due to sparse acquisition, inter-slice motion, and the widely varying position and shape of the placenta between pregnant women. We propose a minimally interactive framework that combines multiple volumes acquired in different views to obtain accurate segmentation of the placenta. In the first phase, a minimally interactive slice-by-slice propagation method called Slic-Seg is used to obtain an initial segmentation from a single motion-corrupted sparse volume image. It combines high-level features, online Random Forests and Conditional Random Fields, and only needs user interactions in a single slice. In the second phase, to take advantage of the complementary resolution in multiple volumes acquired in different views, we further propose a probability-based 4D Graph Cuts method to refine the initial segmentations using inter-slice and inter-image consistency. We used our minimally interactive framework to examine the placentas of 16 mid-gestation patients from MRI acquired in axial and sagittal views respectively. The results show the proposed method has 1) a good performance even in cases where sparse scribbles provided by the user lead to poor results with the competitive propagation approaches; 2) a good interactivity with low intra- and inter-operator variability; 3) higher accuracy than state-of-the-art interactive segmentation methods; and 4) an improved accuracy due to the co-segmentation based refinement, which outperforms single volume or intensity-based Graph Cuts.