Medical Image Segmentation

CNN- and Transformer-based architectures have achieved strong performance in medical image segmentation, but CNNs are limited in modeling long-range dependencies, while Transformers often suffer from quadratic computational and memory complexity. State space models, especially Mamba-based networks, offer an efficient alternative with linear sequence complexity. However, existing Mamba segmentation models still face two limitations: pixel-wise directional scanning can disrupt local 2D spatial structure, and simple summation-based fusion of scan directions cannot adapt well to diverse object sizes, shapes, and boundaries. To address these issues, we propose \textit{Patch-MoE Mamba}, a patch-ordered mixture-of-experts state space architecture for medical image segmentation. It introduces a hierarchical patch-ordered scanning mechanism that preserves local spatial neighborhoods while capturing multi-scale context, and an MoE-based directional fusion module that adaptively combines multiple Mamba scanner outputs using four directional experts, a learnable concatenation expert, and residual directional aggregation. Experiments on five public polyp segmentation benchmarks and the ISIC 2017/2018 skin lesion segmentation datasets demonstrate the effectiveness and generality of Patch-MoE Mamba.

The release of public 3D medical image segmentation (MIS) datasets accelerates clinical research but simultaneously heightens risks of unauthorized AI model training. While Unlearnable Examples (UE) offer protection by injecting imperceptible perturbations to prevent effective model learning, existing methods primarily target 2D scenarios. They neglect the volumetric spatial correlations and inter-slice anatomical consistency inherent in 3D medical volumes, which serve as critical learning priors for 3D segmentation networks. To bridge this gap, we propose VoxShield, a UE framework that explicitly targets the volumetric inductive biases of 3D networks. Our core insight is that by systematically dismantling the cross-slice continuity that 3D architectures rely on, we can fundamentally impair their spatial aggregation process. Specifically, we introduce an Inter-Slice Frequency Consistency Disruption mechanism that maximizes the spectral divergence between adjacent slices, injecting structural incoherence along the $z$-axis. Complementing this structural attack, a Semantic Prediction Disruption module is incorporated. By maximizing the $\ell_1$ divergence between clean and perturbed logits, it forces the injected noise to penetrate the entire network and corrupt the final semantic mapping. Experiments on BraTS19 and FLARE21 demonstrate that VoxShield successfully degrades 3D segmentation performance, reducing the DSC from 80.0% to near 0.0% and from 88.6% to 6.8%, respectively. All protections are achieved with minimal perturbation ($ε=4/255$) to preserve high visual fidelity. The code is available at https://github.com/KK266299/VoxShield.

Accurate segmentation and statistical shape modeling of hand anatomy have significant implications for medical diagnostics, ergonomics, and biomechanics. This study proposes an AI-assisted reconstruction pipeline for segmenting and analyzing hand anatomy from 1,271 elbow-to-hand (e2h-CT) computed tomography scans. A Pix2Pix-based conditional generative adversarial network is first employed to remove plaster cast and background artifacts from CT volumes. The cleaned scans are then processed in 3D Slicer to extract skin and bone masks, which are converted into closed-surface mesh models. Segmented bone meshes are used to construct skeletal representations, enabling implicit skinning to align all hand models into a standardized anatomical configuration. Subsequently, non-rigid registration is performed on the hand skin surfaces using the Geodesic Based Coherent Point Drift++ (GBCPD++) algorithm to establish point-wise correspondence across subjects. Principal Component Analysis (PCA) is then applied to the registered models to quantify anatomical shape variability. The Pix2Pix preprocessing stage achieved a Dice coefficient of 0.9856 and an IoU of 0.9720 on the held-out test set. Statistical modeling was performed on a subset of 90 scans in which the fingers were fully visible and anatomically separated. The resulting statistical shape distributions demonstrate strong agreement with the U.S. Army Anthropometric Survey (ANSUR II), supporting the anatomical validity of the reconstructed models. The proposed methodology demonstrates significant potential for advancing biomechanical modeling, ergonomic optimization, prosthetic design, and precision medical diagnostics.

Medical referring image segmentation (MRIS) requires pixel-level masks aligned with textual descriptions of anatomical locations, making annotation costly in low-label regimes. Semi-supervised learning (SSL) can mitigate this burden by leveraging unlabeled data, but its success hinges on maintaining reliable image-text alignment under perturbations. Most existing SSL-based referred segmentation methods use either independent or simplistic multi-modal perturbations (e.g., left-right flips), without fully addressing cross-modal alignment under strong augmentation, while CutMix, highly effective in single-modal SSL, remains underexplored in multi-modal settings due to its tendency to disrupt image-text coherence. We propose Semi-MedRef, a teacher-student SSL framework designed to explicitly maintain consistency between medical images and positional language through three alignment-preserving components: T-PatchMix, a cross-modal CutMix-style augmentation that synchronizes patch mixing with referring expressions via position-constrained and probability-driven rules; PosAug, a position-aware text augmentation that masks or fuzzes anatomical phrases; and ITCL, a position-guided image-text contrastive learning module, which leverages positional pseudo-labels to construct soft anatomical positives and strengthen medically grounded cross-modal alignment. Experiments on QaTa-COV19 and MosMedData+ demonstrate that Semi-MedRef consistently outperforms both fully supervised and semi-supervised baselines across all label regimes.

Accurate medical image segmentation is fundamental to precision medicine, yet robust delineation remains challenging under heterogeneous appearances, ambiguous boundaries, and large anatomical variability. Similar intensity and texture patterns between targets and surrounding tissues often lead to blurred activations and unreliable separation. We attribute these failures to representation collapse during encoding and insufficient fine grained multi scale decoding. To address these issues, we propose Med DisSeg, a dispersion driven medical image segmentation framework that jointly improves representation learning and anatomical delineation. Med DisSeg combines a lightweight Dispersive Loss with adaptive attention for fine grained structure segmentation. The Dispersive Loss enlarges inter sample margins by treating in batch hidden representations as negative pairs, producing well dispersed and boundary aware embeddings with negligible overhead. Based on these enhanced representations, the encoder strengthens structure sensitive responses, while the decoder performs adaptive multi scale calibration to preserve complementary local texture and global shape information. Extensive experiments on five datasets spanning three imaging modalities demonstrate consistent state of the art performance. Moreover, Med DisSeg achieves competitive results on multi organ CT segmentation, supporting its robustness and cross task applicability.

Medical image segmentation remains challenging in low-data regimes, where scarce annotations often yield poor generalization and ambiguous boundaries with missing fine structures. Recent self-supervised pretraining has improved transferability, but it often exhibits a texture bias. In contrast, accurate segmentation is inherently geometry-aware and depends on both topological consistency and precise boundary preservation. To address this problem, we propose a two-stage framework that couples structure-aware encoder pretraining with boundary-oriented decoding. In Stage-1, we aim to learn structure-aware representations for downstream segmentation in low-data regimes. To this end, we propose Mixed-Domain MeanFlow Pretraining, which aligns images and binary masks in a shared latent space through latent transport regression, where masks act as conditional structural guidance rather than prediction targets, making the pretraining task-agnostic. To further improve training stability under scarce supervision, we incorporate a lightweight Dispersive Loss to prevent representation collapse. In Stage-2, we fine-tune the pretrained encoder with a lightweight decoder that combines Direct Attentional Fusion for adaptive cross-scale gating and Frequency-Directional Dynamic Convolution for high-frequency boundary refinement under appearance variation. Experiments on ISIC-2016, Kvasir-SEG, and GlaS demonstrate consistent gains over state-of-the-art methods, with improved robustness in low-data settings and sharper boundary delineation.

INTRODUCTION | Fully supervised 3D segmentation of high-resolution ex vivo MRI is limited by the prohibitive cost of volumetric annotation, forcing reliance on sparse 2D slices. Weakly supervised Sparse-to-Dense frameworks bridge this gap, but guidelines remain ambiguous regarding human-centric visual enhancements and transferring optimization strategies across dimensions. We analyze divergent regularization needs for multi-class segmentation of high-resolution ex vivo spinal cord MRI. METHODS | We used 9.4T MRI of multiple sclerosis spinal cords (>104,000 slices) with sparse annotations (428 slices). A 2D Teacher trained on sparse slices generated dense pseudo-labels to train a 3D Student. We systematically evaluated the impact of human-centric preprocessing, spatial augmentation, and soft-label regularization on both architectures. RESULTS | We identified a critical divergence in training dynamics. The 2D Teacher required strong spatial augmentation and soft-labeling to overcome data scarcity, improving White Matter Lesion Dice scores by >11 points. However, propagating these techniques to the 3D Student degraded its performance. Furthermore, human-centric preprocessing (e.g., CLAHE) disrupted global statistical cues, dropping Gray Matter Lesion Dice scores by ~25 points. DISCUSSION | Our study highlights a perception divergence (human-centric contrast enhancement harms machine models) and a regularization conflict across dimensions. 3D architectures trained on dense pseudo-labels exhibit fundamentally different optimization landscapes than 2D counterparts and require distinct, conservative regularization. Code and models: https://github.com/ivadomed/model_seg_sc-gm-lesion_human_ms_exvivo_t2star.

Semantic segmentation is essential for analysing anatomical features in biomedical research, yet a performance gap remains for Vision Transformers (ViTs) in the field, particularly for sparse, fine-structured, and low signal-to-noise targets. We attribute this challenge in part to the lightweight pixel decoders commonly used in promptable ViT models, who may lack the local inductive bias needed for high-precision biomedical masks. We bridge this gap by introducing ViTC-UNet, which conditions a UNet on frozen pre-trained ViT representations through learnable tokens and a two-way attention decoder. This combines ViT global visual priors with the local inductive bias and high-resolution decoding capacity of UNets, while avoiding end-to-end ViT fine-tuning even in cross-domain settings. ViTC-UNet outperforms baseline results in semantic segmentation tasks across MRI and CT modalities, demonstrating that structure-conditioned UNet decoding can efficiently adapt large-scale visual priors to high-complexity biomedical segmentation.

Accurate medical image segmentation is an integral part of the medical image analysis pipeline that requires the ability to merge local and global information. While vision transformers are able to capture global interactions using vanilla self-attention, their quadratic computational complexity in the input size remains a struggle for medical image segmentation tasks. Motivated by the dispersion property of vanilla self-attention and recent development of Mamba form of attention, Scalable and Efficient Mamba like Attention (SEMA) utilizes token localization via local window attention to avoid dispersion and maintain focusing, complemented by theoretically consistent arithmetic averaging to capture global aspect of attention. In this work, we present USEMA, a hybrid UNet architecture that merges the local feature extraction ability of convolutional neural networks (CNNs) with SEMA attention. We conduct experiments with USEMA across a variety of modalities and image sizes, demonstrating improved computational efficiency compared to transformer based models using full self-attention, and superior segmentation performance relative to purely convolution and Mamba-based models.

Split Federated Learning (SplitFed) combines federated and split learning to preserve privacy while reducing client-side computation. However, in medical image segmentation, heterogeneous label quality across clients can significantly degrade performance. We propose SplitFed-CL, a co-learning framework where a global teacher guides local students to detect and refine unreliable annotations. Reliable labels supervise training directly, while unreliable labels are corrected via weighted student--teacher refinement. SplitFed-CL further incorporates consistency regularization for robustness to input perturbations and a trainable weighting module to balance loss terms adaptively. We also introduce a novel difficulty guided strategy to simulate human like boundary centric annotation errors, where the degree of perturbation is governed by shape complexity and the associated annotation difficulty. Experiments on two multiclass segmentation datasets with controlled synthetic noise, together with a binary segmentation dataset containing real-world annotation errors, demonstrate that SplitFed-CL consistently outperforms seven state-of-the-art baselines, yielding improved segmentation quality and robustness.

Data-driven medical AI is traditionally formulated as a discriminative mapping from input $X$ to output $Y$ via a learned function $f$, which does not generalize well across heterogeneous data and modalities encountered in real-world clinical settings. In this work, we propose a fundamentally different, generative paradigm. We model the joint distribution $P(X,Y)$ using diffusion models and reframe inference as a test-time output optimization problem. By guiding the generative process to match observed inputs, our framework enables flexible, gradient-based conditioning at inference time without architectural changes or retraining, effectively supporting arbitrary and previously unseen combinations of observations. Extensive experiments demonstrate strong performance across standard and cross-modality medical image segmentation, few-shot segmentation with only 2 or 4 training samples, degraded-input segmentation, shape completion from sparse and partial observations, and zero-shot application to demonstrate generality. To support these evaluations, we curated and released a large-scale text-shape dataset derived from MedShapeNet. Our results highlight the versatility of generative joint modeling as a foundation for reusable, task-agnostic medical AI systems.

Medical image segmentation models can perform unevenly across subgroups. Most existing fairness methods focus on improving average subgroup performance, implicitly treating each subgroup as internally homogeneous. However, this can hide difficult cases within a subgroup, where high-loss samples are obscured by the subgroup mean. We call this problem \textbf{intra-group hidden failure}. To solve this, we propose \textbf{DuetFair} mechanism, a dual-axis fairness framework that jointly considers inter-subgroup adaptation and intra-subgroup robustness. Based on DuetFair, we introduce \textbf{FairDRO}, which combines distribution-aware mixture-of-experts (dMoE) with subgroup-conditioned distributionally robust optimization (DRO) loss aggregation. This design allows the model to adapt across subgroups while also reducing hidden failures within each subgroup. We evaluate FairDRO on three medical image segmentation benchmarks with varying degrees of within-group heterogeneity. FairDRO achieves the best equity-scaled performance on Harvard-FairSeg and improves worst-case subgroup performance on HAM10000 under both age- and race-based grouping schemes. On the 3D radiotherapy target cohort, FairDRO further improves worst-group Dice by 3.5 points ($\uparrow 6.0\%$) under the tumor-stage grouping and by 4.1 points ($\uparrow 7.4\%$) under the institution grouping over the strongest baseline.

Medical image segmentation is a critical task in computer-aided diagnosis and treatment planning. However, deep learning models often struggle to generalize across datasets due to domain shifts arising from variations in imaging protocols, scanner types, and patient populations. Traditional domain generalization (DG) methods utilize causal feature learning, adversarial consistency, and style augmentation to improve segmentation robustness. While effective, these approaches rely on explicit feature alignment, adversarial objectives, or handcrafted augmentations, which may not fully exploit the capabilities of foundation models. Recently, the Segment Anything Model (SAM) has demonstrated strong generalization capabilities in segmentation tasks. SAM-based DG methods attempt to improve medical image segmentation. However, these approaches primarily operate in the spatial domain and overlook frequency-based discrepancies that significantly affect model robustness. In this work, we propose Frequency-based Domain Generalization with SAM (FSAM), a novel framework that integrates Low-Rank Adaptation (LoRA) for efficient fine-tuning and a frequency adapter to incorporate frequency-domain representations for single-source domain generalization. FSAM enhances SAM's segmentation robustness by extracting domain-invariant high-frequency features, mitigating frequency-related domain shifts. Experimental results on fundus and prostate datasets demonstrate that FSAM outperforms existing traditional DG and SAM-based DG approaches in domain generalization. Codes and pre-trained models will be made available on GitHub.

Modern computer vision systems increasingly encounter performance limitations in data-scarce domains, where collecting large-scale, high-quality labeled data is costly or impractical. While controllable diffusion models enable scalable synthetic image generation, directly applying synthetic augmentation often leads to unstable performance gains due to dataset-level quality issues and insufficient feedback mechanisms. In this work, we present a Real-Calibrated Synthetic-First Data Engine, a modular data engineering framework that combines controllable diffusion generation and multi-stage curation/filtering within a unified pipeline, with optional support for uncertainty-driven selection and human verification. Instead of introducing new generative algorithms, our approach focuses on systematic dataset construction for improving the practical reliability of synthetic augmentation in low-data regimes. The framework is implemented as a modular CLI-based pipeline, where generation, filtering, selection, and validation components can be independently configured and replaced. This design emphasizes reproducibility, flexibility, and practical deployment in real-world data workflows. Through empirical evaluation centered on human pose estimation, we show that synthetic data improves a real-data baseline when used as near-zero-human-annotation-cost augmentation alongside real anchors, while synthetic-only training remains substantially below real-only performance. Supplementary segmentation diagnostics show the same domain-gap pattern. These results highlight the practical value of data-centric orchestration for low-data augmentation.

While U-Net architectures remain the gold standard for medical image segmentation, their deployment in resource-constrained environments demands aggressive model compression. However, finding an optimally efficient configuration is computationally prohibitive, typically requiring exhaustive train-and-evaluate cycles to find the smallest model that maintains peak performance. In this paper, we introduce a training-free selection framework to automatically identify ultralightweight, dataset-specific U-Net configurations directly at initialization. We observe that systematically scaling down U-Net channel width induces a sharp transition from a stable performance plateau to representational capacity collapse. To pinpoint this boundary without training, we propose a Jacobian-based sensitivity metric that scores discrete, width-capped U-Net variants using a small set of unlabeled images. By analyzing the total variation of this sensitivity curve, we isolate the smallest stable configuration, which we denote as XTinyU-Net. Evaluated across six diverse medical datasets within the nnU-Net framework, XTinyU-Net achieves segmentation accuracy comparable to the heavy nnU-Net baseline with 400x-1600x fewer parameters, and outperforms contemporary lightweight architectures while utilizing 5x-72x fewer parameters. Code is publicly accessible on https://github.com/alvinkimbowa/nntinyunet.git.

Purpose: To develop and evaluate cross-sequence transfer learning for automatic femoral cartilage segmentation, testing bidirectional transfer between dual-echo steady-state (DESS) and sagittal proton density-weighted 3D fast spin-echo (Cube) sequences. Materials and Methods: We optimized a modified 2D U-Net on 507 DESS images from the Osteoarthritis Initiative (OAI). We then established same-sequence baselines using subject-level cross-validation on a subset of 44 OAI DESS images and 44 Cube images acquired at the Istituto Ortopedico Rizzoli, Bologna, Italy. Each subset included 22 non-lesioned and 22 lesioned subjects. Finally, we performed transfer learning across sequences by fine-tuning the pretrained models on the target sequence with increasing training set sizes to study convergence, while keeping validation and test sets fixed. Segmentations were evaluated using Dice similarity coefficient (DSC) and average surface distance (ASD). Lesion effects were assessed with two-sided Mann-Whitney U tests with Bonferroni correction. Results: Same-sequence training yielded higher accuracy on DESS than Cube (DSC, $0.900$ vs $0.830$; $P < .001$). Cube-to-DESS transfer matched DESS performance (DSC, $0.903 \pm 0.032$ vs $0.900 \pm 0.027$), reaching a performance plateau at 9 training subjects. DESS-to-Cube yielded a lower combined DSC ($0.802 \pm 0.049$ vs $0.830 \pm 0.042$), reaching a plateau at 24 training subjects. Lesions did not affect DESS ($P \ge .39$) but reduced Cube accuracy (DSC, $0.805$ vs $0.856$; $P < .001$). Conclusion: Transfer learning across sequences can substantially reduce target-sequence annotation requirements for femoral cartilage segmentation, but performance is direction- and sequence-dependent, and the effects of lesions on segmentation may vary across MRI sequences.

Uncertainty quantification complements model predictions by characterizing their reliability, which is essential for high-stakes decision making such as medical image segmentation. However, most existing methods reduce uncertainty to a scalar confidence estimate, leaving its spatial distribution semantically underconstrained. In this work, we focus on uncertainty interpretability, namely, whether estimated uncertainty behaves in a human-understandable manner with respect to sources of ambiguity. We identify three perception-aligned principles requiring the spatial distribution of uncertainty to reflect: (1) image contrast between structures, (2) severity of image corruption, and (3) geometric complexity in anatomical structures. Accordingly, we develop a principle-guided uncertainty supervision framework (PriUS) based on evidential learning, in which the corresponding supervision objectives are explicitly enforced during training. We further introduce quantitative metrics to measure the consistency between predicted uncertainty and image attributes that induce ambiguity. Experiments on ACDC, ISIC, and WHS datasets showed that, compared with state-of-the-art methods, PriUS produced more consistent uncertainty estimates while maintaining competitive segmentation performance.

Multiple sclerosis (MS) expresses substantial clinical and radiological heterogeneity, which poses significant challenges for automatic lesion segmentation. The current deep learning-based SOTA is highly susceptible to changes in both distribution, e.g., changes in scanner; as well as the structure of inputs, evident in the current divide between cross-sectional and longitudinal approaches. We introduce TimeLesSeg, a unified contrast-agnostic framework designed to segment MS lesions regardless of the presence of a temporal dimension in its inputs, with a single convolutional neural network. Our approach models pathological priors through lesion masks, which are processed together with the current scan. Cross-sectional processing is enabled by exposing the model to training cases where no prior information is available, which are modeled with an empty mask, allowing it to operate seamlessly in both scenarios. To overcome the scarcity and inconsistency of longitudinal datasets, we propose a novel generative pipeline in which patterns of lesion evolution are simulated by stochastically deforming each individual lesion with morphological operations, producing realistic prior timepoints. In parallel, we achieve contrast agnosticism through Gaussian mixture model-based domain randomization, enabling the network to experience a wide spectrum of intensity profiles. Results on three publicly available and two in-house datasets show that TimeLesSeg outperforms the contrast-agnostic state of the art on single-modality inputs across overlap- and distance-based metrics. In longitudinal processing, our method outperforms SAMSEG, and captures lesion load dynamics more accurately than both the former and LST-AI. All source code related to the development of TimeLesSeg is available at https://github.com/NeuroADaS-Lab/TimeLesSeg.

Adapting foundation models to medical segmentation typically requires either backbone fine-tuning or high-capacity task-specific decoders, both of which are difficult to fit reliably when annotations are scarce. We show that frozen DINOv3 features already contain useful structural and boundary cues for medical segmentation, and that the main bottleneck lies in how these features are read out. We propose DINO-MVR, a Multi-View Readout framework for annotation-efficient medical segmentation. DINO-MVR trains only lightweight MLP probes on features from the final three transformer blocks of a frozen DINOv3 backbone, without updating the backbone itself. At inference, each input is interpreted through complementary resolutions and test-time augmentations, whose probability maps are combined by entropy-weighted fusion and refined with simple spatial regularization. For volumetric inputs, Gaussian z-axis smoothing further improves inter-slice consistency. Under fixed evaluation protocols on endoscopy, dermoscopy, and MRI benchmarks, DINO-MVR achieves strong readout-only performance, including 0.895 Dice on Kvasir-SEG, 0.897 Dice on ISIC 2018, and 0.908 Dice on BraTS FLAIR whole-tumor segmentation. With only five annotated BraTS patients, it recovers 98.4% of the performance obtained by the 40-patient BraTS reference run. These results suggest that frozen self-supervised vision backbones can support accurate medical segmentation when paired with an effective multi-view readout.

Curating fully annotated datasets for medical image segmentation is labour-intensive and expertise-demanding. To alleviate this problem, prior studies have explored scribble annotations for weakly supervised segmentation. Existing solutions mainly compute losses on annotated areas and generate pseudo labels by propagating annotations to adjacent regions. However, these methods often suffer from inaccurate and unrealistic segmentations due to insufficient supervision and incomplete shape information. In contrast, we first investigate the principle of good scribble annotations, which leads to efficient scribble forms via supervision maximization and randomness simulation. We further introduce regularization terms to encode the spatial relationship and the shape constraints, where the EM algorithm is utilized to estimate the mixture ratios of label classes. These ratios are critical in identifying the unlabeled pixels for each class and correcting erroneous predictions, thus the accurate estimation lays the foundation for the incorporation of spatial prior. Finally, we integrate the efficient scribble supervision with the prior into a framework, referred to as ZScribbleSeg, and apply it to multiple scenarios. Leveraging only scribble annotations, ZScribbleSeg achieves competitive performance on six segmentation tasks including ACDC, MSCMRseg, BTCV, MyoPS, Decathlon-BrainTumor and Decathlon-Prostate. Our code will be released via https://github.com/DLwbm123/ZScribbleSeg.

Continual learning (CL) is essential for deploying medical image segmentation models in clinical environments where imaging domains, anatomical targets, and diagnostic tasks evolve over time. However, continual segmentation still faces three main challenges. First, the scenarios for this task remain insufficiently standardized for real-world clinical settings. Second, existing research has been primarily focused on mitigating forgetting, overlooking the other essential properties such as plasticity. Third, a benchmark work with comprehensive evaluation on existing methods is stll desirable. To address these gaps, we present such benchmark study of continual medical image segmentation. We first define three clinically motivated scenarios, namely Domain-CL, Class-CL, and Organ-CL, to respectively capture the cross-center domain shift, the incremental anatomical structure segmentation, and the cross-organ segmentation. We then introduce an evaluation framework that measures not only general performance and forgetting, but also plasticity, forward generalizability, parameter efficiency, and replay burden. The results, from extensive experiments with representative CL methods, showed that it was still challenging to develop a model that could satisfy all the requirements simultaneously. Nevertheless, these studies also suggested that the replay-based methods achieve the best overall balance between stability and plasticity, the parameter-isolation methods should be effective at reducing forgetting, though at the cost of increased model size, and the forward generalizability remain a significantly understudied aspect of this research field. Finally, we discuss related learning paradigms and outline future directions for continual medical image segmentation.

Segment Anything Model 2 (SAM2) demonstrated impressive zero-shot capabilities on natural images but faces challenges in biomedical segmentation due to significant domain shifts and prompt dependency. To address these limitations, we propose a prompt-free, parameter-efficient fine-tuning framework designed for multi-class segmentation on variable-sized inputs. We introduce a convolutional Positional Encoding Generator to adapt effectively to arbitrary aspect ratios and present a dual-adapter strategy: High-Performance Adapter utilizing deformable convolutions for precise boundary modeling and Lightweight Adapter employing structural re-parameterization to minimize inference latency. Experiments on ISBI 2012, Kvasir-SEG, Synapse, and ACDC datasets demonstrate that our approach significantly outperforms strong adaptation baselines. Specifically, our method improved segmentation accuracy by up to 19.66% over the vanilla SAM2, while reducing computational costs by approximately 87% compared to heavyweight medical SAM adaptations, establishing a superior trade-off between accuracy and efficiency.

Rheumatoid arthritis (RA) assessment from hand radiographs requires multi-level analysis and modeling of anatomical structures and fine-grained local pathological changes. However, existing public resources do not support such unified multi-level analysis, often lacking full-hand coverage, fine-grained annotations, and consistent integration with clinical scoring systems. In particular, annotations that enable quantitative analysis of bone erosion (BE) remain scarce. RAM-H1200 contains 1,200 hand radiographs collected from six medical centers, with multi-level annotations including (i) whole-hand bone structure instance segmentation, (ii) pixel-level BE masks, (iii) SvdH-defined joint regions of interest, and (iv) joint-level SvdH scores for both BE and joint space narrowing (JSN). It is designed to evaluate whether models can jointly capture anatomical structure, localized erosive pathology, and clinically standardized RA severity from hand radiographs. The proposed BE masks enable, for the first time, quantitative BE analysis beyond coarse categorical grading by providing explicit spatial supervision for lesion extent and morphology. To our knowledge, RAM-H1200 is the first public large-scale benchmark that jointly supports whole-hand bone structure instance segmentation, pixel-level BE delineation, and clinically grounded joint-level SvdH scoring for both BE and JSN. Results across benchmark tasks show that anatomical modeling is substantially more mature than quantitative BE analysis: whole-hand bone segmentation achieves strong performance, whereas BE segmentation remains a major open challenge. By unifying anatomical structure modeling, quantitative lesion analysis, and clinically grounded SvdH scoring, RAM-H1200 provides a single benchmark for comprehensive RA analysis on hand radiographs.

Anatomical mesh segmentation requires models that operate directly on irregular surface geometry while remaining robust to arbitrary patient pose and mesh resolution variation. Existing task-specific mesh and point-cloud methods are not equivariant, and can degrade sharply under test-time perturbation, for example dropping by 25-26 IoU points on intraoral scan segmentation at $40^\circ$ tilt. We present EAMS, an Equivariant Anatomical Mesh Segmentor built on Equivariant Mesh Neural Networks (EMNN), and evaluate it across four clinically distinct tasks spanning edge-, vertex-, and face-level supervision. We combine intrinsic mesh descriptors with anatomy-aware priors, including PCA-derived frames for dental arches and liver surfaces, and augment message passing to provide lightweight global context. Across intracranial aneurysm and intraoral segmentation, EAMS variants are competitive with specialized baselines on unperturbed inputs while remaining stable under geometric perturbations, and on liver surfaces they expose a favorable trade-off between canonical-pose accuracy and rotation robustness. These results show that a lightweight ($<2$M parameters) equivariant framework can deliver robust anatomical mesh segmentation across diverse supervision types without task-specific architectures.

Deep learning-based medical image segmentation is increasingly used to support clinical diagnosis and develop new treatment strategies. However, model performance remains limited by the scarcity of high-quality annotated data and insufficient generalization across imaging protocols. This limitation is particularly evident in MRI and CT, where models are typically trained on a single acquisition sequence and exhibit reduced robustness when applied to unseen sequences or contrasts. Although data augmentation is widely used to improve general robustness on medical images, its impact on cross-modality generalization has not been quantitatively explored. In this work, we study a targeted set of data augmentation techniques designed to improve cross-modality transfer. We train three spine segmentation models, each on a single-modality/sequence dataset, and evaluate them across seven out-of-distribution datasets (spanning CT and MRI), reflecting a realistic single-sequence training and multi-sequence/contrast/modality deployment scenario. Our results demonstrate substantial performance gains on unseen domains (average Dice gain of 155 %) while preserving in-domain accuracy (average Dice decrease of 0.008 %), including effective transfer between CT and MRI. To mitigate the computational cost typically associated with strong data augmentation, we implement GPU-optimized augmentations that maintain, and even improve, training efficiency by approximately 10 %. We release our approach as an open-source toolbox, enabling seamless integration into commonly used frameworks such as nnUNet and MONAI. These augmentations significantly enhance robustness to heterogeneous clinical imaging scenarios without compromising training speed.

Organoids are complex, three dimensional, self-organizing cell cultures which manifest organ-like features and represent a powerful platform for studying human disease and developing treatment options. Organoid development is characterized by dynamic morphological and cellular organization, which mimic some aspects of organ development. To study these rapid changes over the course of organoid development, advanced imaging and analytical tools are critical to accurately monitor the trajectory of organoid growth and investigate disease processes. In this work, we focus on computer vision and machine learning techniques to automatically measure the size and shape of developing spheroids derived from pluripotent stem cells (iPSCs), which are typically the starting material for generating organoid cultures. To facilitate this task, we introduce a composite method that combines the Segment Anything Model (SAM), a general-purpose foundation model, with an existing domain-specific tool. This composite method is evaluated together with several existing tools by testing them on organoid image data and comparing with the results of manual image segmentation. We find that no single existing tool is able to segment the test images with sufficient accuracy across all test conditions, but the newly introduced composite method produces consistent and accurate results for all but a very small fraction of the most challenging images. Finally, we compare the accuracy of this method to the variability between manual segmentations by independent annotators (inter-observer variability) and find that by one measure it performs at the level of inter-observer variability and by others it performs very close to it.

Federated Learning enables decentralized training by aggregating model updates across clients without sharing raw data, while Split Federated Learning further partitions the model between clients and a server to reduce computation and communication at the client side. However, decentralized medical institutions rarely operate on a single shared task, making standard Federated and SplitFed collaborations poorly aligned with real clinical workflows. Multi-task FL extends these frameworks by allowing clients to handle different tasks, but often introduces instability and privacy vulnerabilities. This study proposes \textbf{MuCALD-SplitFed}, a multi-task SplitFed framework that integrates causal representation learning and latent diffusion. Experiments show MuCALD-SplitFed consistently improves segmentation, while baseline SplitFed fails to converge. The proposed approach further reduces information leakage at split points, mitigating reconstruction-based and membership inference attacks. Additionally, MuCALD SplitFed outperforms state-of-the-art personalized FL and multi-task FL approaches. The code repository is: https://github.com/ChamaniS/MuCALD_SplitFed.

Active learning (AL) has emerged as a crucial strategy for reducing the prohibitive costs associated with medical image segmentation. However, standard uncertainty-based AL methods typically focus on maximizing performance metrics, ignoring performance disparities or fairness across groups with sensitive attributes. While fair active learning has been explored in classification tasks, its intersection with medical image segmentation remains unaddressed. In this work, we introduced a fairness-aware active learning framework with a Weighted Entropy selection strategy that modulates uncertainty based on current group-specific performance estimates on the labeled set. To decouple true epistemic uncertainty from anatomical volume variances, we further utilized a masked, scaled entropy restricted to the region of interest. The framework was evaluated on synthetic T1-weighted brain MRIs with controlled left caudate bias in both strong and weak bias settings. A 3D U-Net was trained to segment the left caudate under several AL strategies, starting from both demographically balanced and strongly imbalanced initial labeled sets. Experiments demonstrated that our method markedly reduces performance disparities between groups compared to random sampling and standard uncertainty sampling. By prioritizing poorly segmented subgroups during the AL cycles, our method consistently achieved the highest equity-scaled performance and reduced the disparity metric by 75% (strong bias) and 86% (weak bias) relative to standard entropy at the final budget. Overall, this work is among the first studies on fair AL for medical image segmentation, offering an efficient strategy to train more equitable models in resource-constrained environments.

We propose a unified cross-domain transfer learning framework that leverages knowledge from multiple heterogeneous medical imaging datasets to improve performance across segmentation, classification, and object detection tasks. Our approach employs a teacher-student paradigm in which a joint teacher model aggregates domain-invariant representations learned from diverse source datasets, while a task-specific student model is trained via multi-level knowledge distillation. Originally developed for medical image segmentation, the framework is extended to support image-level classification and object-level detection, enabling a general multi-task formulation for medical image analysis. We evaluate our method on a broad suite of datasets, including six segmentation benchmarks, BrainMetShare, ISLES, BraTS (MRI) and Lung MSD, LiTS, KiTS (CT), as well as multiple classification datasets for pulmonary disease and dementia, and detection datasets with native bounding-box annotations. Across all tasks and modalities, the proposed approach yields consistent improvements over strong dataset-specific and multi-head baselines, demonstrating enhanced robustness to distributional shifts and superior generalization. These findings highlight the potential of multi-dataset knowledge distillation as a scalable and task-agnostic approach for enhancing segmentation, classification, and object detection performance across heterogeneous medical imaging domains.

Accurate lesion segmentation is crucial for clinical diagnosis and treatment planning. However, lesions often resemble surrounding tissues and exhibit ill-defined boundaries, leading to unstable predictions in boundary/transition regions. Moreover, small-lesion cues can be diluted by multi-scale feature extraction, causing under- or over-segmentation. To address these challenges, we propose an Uncertainty-Aware Hypergraph Refinement Network (UHR-Net). First, we introduce an Uncertainty-Oriented Instance Contrastive (UO-IC) pretraining strategy that couples geometry-aware copy-paste augmentation with hard-negative mining of lesion-like background regions to improve instance-level discrimination for small and visually ambiguous lesions. Second, we design an Uncertainty-Guided Hypergraph Refinement (UGHR) block, which derives an entropy-based uncertainty map from a coarse probability map to guide hypergraph refinement. By splitting hyperedge prototypes into foreground and background groups, UGHR decouples higher-order interactions and improves refinement in ambiguous regions. Experiments on five public benchmarks demonstrate consistent gains over strong baselines. Code is available at: https://github.com/CUGfreshman/UHR-Net.

Peritoneal metastases (PM) are staged using the surgically determined Peritoneal Cancer Index (sPCI), which requires invasive laparoscopic assessment. Although CT is routinely used for preoperative evaluation, imaging-based assessment of PM extent remains challenging and is often less structured than surgical PCI scoring. A recent consensus study defined radiological PCI (rPCI) regions for cross-sectional imaging. We present the first deep learning approach to automatically segment 13 rPCI regions on CT. 62 contrast-enhanced CT scans were retrospectively collected across the full PCI range. Each scan was annotated into non-overlapping rPCI regions by one researcher, reviewed by a second, with disagreements resolved by a radiologist. Using five-fold cross-validation, we compared nnU-Net and Swin UNETR with Dice, 95th-percentile Hausdorff distance (HD95) and Average Surface Distance (ASD). We introduce an anatomically constrained pipeline that trains on merged super-regions and splits them during post-processing using TotalSegmentator landmarks at the hips and the ligament of Treitz. On this 62-scan cohort, the baseline nnU-Net reached an overall Dice of 0.81 and outperformed Swin UNETR (0.76). The proposed pipeline improved the overall Dice to 0.84 and reduced boundary error (HD95 13.7 to 11.8 mm; ASD 4.1 to 3.4 mm), with the largest gains in the small-bowel regions, approaching the interobserver Dice of 0.87. Automated rPCI region segmentation on CT is feasible and approaches interobserver agreement. Encoding anatomical boundary constraints substantially improves segmentation quality in the most challenging regions. This provides a reproducible foundation for non-invasive, imaging-based PCI assessment. The main limitations are the single-center cohort and the small interobserver subset.

Purpose: Rapid and reliable diagnostic tools are crucial for managing respiratory diseases like COVID-19, where chest X-ray analysis coupled with artificial intelligence techniques has proven invaluable. However, most existing works on X-ray images have not considered lung segmentation, raising concerns about their reliability. Additionally, some have employed disproportionate and impractical augmentation techniques, making models less generalized and prone to overfitting. This study presents a critical analysis of both issues and proposes a methodology (SDL-COVID) for more reliable classification of chest X-rays for COVID-19 detection. Methods: We use class activation mapping to obtain a visual understanding of the predictions made by Convolutional Neural Networks (CNNs), validating the necessity of lung segmentation. To analyze the effect of data augmentation, deep learning models are implemented on two levels: one for an augmented dataset and another for a non-augmented dataset. Results: Careful analysis of X-ray images and their corresponding heat maps under expert medical supervision reveals that lung segmentation is necessary for accurate COVID-19 prediction. Regarding data augmentation, test accuracy significantly drops beyond a certain threshold with additional augmented images, indicating model overfitting. Conclusion: Our proposed methodology, SDL-COVID, achieves a precision of 95.21% and a lower false negative rate, ensuring its reliability for COVID-19 detection using chest X-rays.

Text guided 3D medical image segmentation offers a flexible alternative to class based and spatial prompt based models by allowing users to specify regions of interest directly in natural language. This paradigm avoids reliance on predefined label sets, reduces ambiguous outputs, and aligns more naturally with clinical workflows. However, existing text guided frameworks are often computationally expensive, exhibit weak text volume feature alignment, and fail to capture fine anatomical details. We propose ESICA, a lightweight and scalable framework that addresses these challenges through three innovations: (1) a similarity matrix based mask prediction formulation that enhances semantic alignment, (2) an efficient decomposed decoder with adapter modules for accurate volumetric decoding, and (3) a two pass refinement strategy that sharpens boundaries and resolves uncertain regions. To improve training stability and generalization, ESICA adopts a two stage scheme consisting of positive only pretraining followed by balanced fine tuning. On the CVPR BiomedSegFM benchmark spanning five imaging modalities (CT, MRI, PET, ultrasound, and microscopy), ESICA achieves state of the art segmentation accuracy, while the compact ESICA4 Lite variant attains similar segmentation performance with substantially fewer parameters, yielding a superior efficiency accuracy trade off. Our framework advances text guided segmentation toward efficient, scalable, and clinically deployable systems. Code will be made publicly available at https://github.com/mirthAI/ESICA.

Semi-supervised learning (SSL) has become a promising solution to alleviate the annotation burden of deep learning-based medical image segmentation models. While recent advances in foundation model-driven SSL have pushed the boundary to extremely limited annotation scenarios, they fail to maintain robust competitive performance in complex imaging modalities. In this paper, we propose SemiSAM-O1, an annotation-efficient framework using only one annotated template image for segmentation. SemiSAM-O1 extends the specialist-generalist collaborative learning framework to the extreme one-label setting by fully exploiting the foundation model's feature representation capability beyond its prompting interface. SemiSAM-O1 operates in two stages. In the first stage, the foundation model's encoder extracts dense features from all volumes, and class prototypes derived from the single annotated template are propagated to the unlabeled pool via feature similarity to produce coarse initial pseudo-labels. In the second stage, an iterative training-and-refinement loop progressively improves both the segmentation model and the pseudo-labels over multiple rounds, where each round trains the model from scratch on current pseudo-labels and generates updated predictions with voxel-wise uncertainty estimates. An uncertainty-guided refinement step further leverages the foundation model's global feature space to correct high-uncertainty regions by aggregating labels from their most similar confident neighbors, establishing a virtuous cycle of mutual improvement. Extensive experiments on a wide range of segmentation tasks across different modalities and anatomical targets demonstrate that SemiSAM-O1 significantly narrows the performance gap between one-label semi-supervised learning and full supervision, while significantly reducing the computational overhead of online foundation model inference.

Semi-supervised learning addresses label scarcity and high annotation costs in medical image segmentation by exploiting the latent information in unlabeled data to enhance model performance. Traditional discriminative segmentation relies on segmentation masks, neglecting feature-level distribution constraints. This limits robust semantic representation learning and adaptive modeling of unlabeled data in scenarios with few labels. To address these limitations, we propose SemiGDA, a novel Generative Dual-distribution Alignment framework for semi-supervised medical image segmentation. Our SemiGDA overcomes the reliance of discriminative methods on large labeled datasets by aligning feature and semantic distributions to boost semantic learning and scene adaptability. Specifically, we propose a Dual-distribution Alignment Module (DAM), which employs two structurally distinct encoders to model image and mask feature distributions. It enforces their alignment in the latent space via distributional constraints, establishing structured feature consistency. Moreover, we design a Consistency-Driven Skip Adapter (CDSA) strategy, which introduces dual skip adapters (Image and Mask) to fuse multi-scale features via skip connections. Using a consistency loss, CDSA enhances cross-branch semantic alignment and reinforces fine-grained semantic consistency. Experimental results on diverse medical datasets show that our method outperforms other state-of-the-art semi-supervised segmentation methods. Code is released at: https://github.com/taozh2017/SemiGDA.

This work introduces DyABD, a novel and complex benchmark dataset of dynamic abdominal MRIs from patients with abdominal hernias and associated high quality abdominal muscle annotations. DyABD is the first-of-its-kind in four key ways; (1) it proposes the first abdominal muscle segmentation task, (2) the dynamic MRIs are acquired whilst the patients perform various exercises, introducing extreme anatomical variability, making it one of the most challenging segmentation datasets to date, (3) it includes both pre and post corrective MRIs and (4) DyABD promotes clinical research into the high recurrence rates of abdominal hernias. Beyond dataset introduction, this work provides a comprehensive evaluation of the generalisation capabilities of existing segmentation models across Supervised, Few Shot and Zero Shot paradigms on the unseen DyABD dataset. This work reveals that there is still room for substantial improvement in the field of medical image segmentation, with the majority of techniques achieving a Dice Coefficient of 0.82. This work therefore sheds light on the true progress of the field and redefines the benchmark for progress in medical image segmentation.

Transformer architectures, including nnFormer,have demonstrated promising results in volumetric medical image segmentation by being able to capture long-range spatial interactions. Although they have high performance, these models need large quantities of labeled training data and are also likely to overfit and become training unstable. This is a serious practical problem because it is not only time-consuming but also expensive to obtain medical images that are annotated by experts. Moreover, fully supervised traditional training pipelines do not take advantage of the available large amounts of unlabeled medical imaging data that can be easily obtained in the clinics. We have solved these drawbacks by advancing the efficiency of the nnFormer with a self-supervised pretraining framework, which is based on the Masked Autoencoders (MAE). In this method, the model is pretrained on unlabeled volumetric medical images to reconstruct randomly masked parts of the input. This allows the encoder to learn meaningful anatomical and structural representations . The encoder is then further fine-tuned on a labeled dataset on the downstream segmentation task. Conducted Experiment shows that the offered method leads to a higher segmentation performance on the count of Dice score, a quicker convergence rate on the course of the fine-tuning procedure, and a superior generalization on the basis of limited labeled data . These findings validate that self-supervised learning combined with transformer-based segmentation models is an appropriate approach to the problem of data shortage in medical image analysis.

Flow matching has recently emerged as a principled framework for learning continuous-time transport maps, enabling efficient ODE-based sampling without relying on stochastic diffusion processes. While generative modeling has shown promise for medical image segmentation, particularly in capturing uncertainty and complex anatomical variability, existing approaches are predominantly based on diffusion models, which require iterative sampling and incur substantial computational overhead. In this work, we propose MedFlowSeg, a conditional flow matching framework that formulates medical image segmentation as learning a time-dependent vector field that transports a simple prior distribution to the target segmentation distribution. Compared to diffusion-based methods, our formulation enables more efficient inference through solving an ordinary differential equation, while preserving the flexibility of generative modeling. To effectively incorporate conditional information, we introduce a dual-conditioning mechanism. Specifically, we propose a Dual-Branch Spatial Attention (DB-SA) module to inject multi-frequency structural priors, and a Frequency-Aware Attention (FA-Attention) module to model interactions between spatial and spectral representations via discrepancy-aware fusion and time-dependent modulation. These components improve the alignment between noisy intermediate states and clean semantic features, leading to better structural consistency and boundary delineation. We conduct extensive experiments across multiple medical imaging modalities, where MedFlowSeg consistently outperforms prior state-of-the-art (SOTA) baselines, including diffusion-based and flow-based methods.

Accurate medical image segmentation requires both long-range contextual reasoning and precise boundary delineation, a task where existing transformer- and diffusion-based paradigms are frequently bottlenecked by quadratic computational complexity and prohibitive inference latency. We propose RF-HiT, a Rectified Flow Hierarchical Transformer that integrates an Hourglass Transformer backbone with a multi-scale hierarchical encoder for anatomically guided feature conditioning. Unlike prior diffusion-based approaches that rely on hundreds of denoising steps, RF-HiT leverages rectified flow with efficient transformer blocks, achieving linear complexity and requiring only a few discretization steps. The model further fuses conditioning features at each resolution via learnable interpolation, enabling effective multi-scale feature integration with minimal computational overhead. As a result, RF-HiT achieves a strong efficiency-performance trade-off, requiring only 10.14 GFLOPs, 13.6M parameters, and inference in as few as 3 steps. Despite its compact design, RF-HiT attains 91.27% mean Dice on ACDC and 87.40% on BraTS 2021, achieving performance comparable to or exceeding that of significantly more intensive architectures. These results suggest that RF-HiT is a promising, computationally efficient foundation for clinical image segmentation.

A key challenge in segmentation in digital histopathology is inter- and intra-stain variations as it reduces model performance. Labelling each stain is expensive and time-consuming so methods using stain transfer via CycleGAN, have been developed for training multi-stain segmentation models using labels from a single stain. Nevertheless, CycleGAN tends to introduce noise during translation because of the one-to-many nature of some stain pairs, which conflicts with its cycle consistency loss. To address this, we propose the Domain Shift Aware CycleGAN, which reduces the presence of such noise. Furthermore, we evaluate several advances from the field of machine learning aimed at resolving similar problems and compare their effectiveness against DSA-CycleGAN in the context of multi-stain glomeruli segmentation. Experiments demonstrate that DSA-CycleGAN not only improves segmentation performance in glomeruli segmentation but also outperforms other methods in reducing noise. This is particularly evident when translating between biologically distinct stains. The code is publicly available at https://github.com/zeeshannisar/DSA-CycleGAN.

Visual prompting has emerged as a powerful method for adapting pre-trained models to new domains without updating model parameters. However, existing prompting methods typically optimize a single prompt per domain and apply it uniformly to all inputs, limiting their ability to generalize under intra and inter-domain variability, which is especially critical in the medical field. To address this, we propose APEX, an Adaptive Prompt EXtraction framework that retrieves input-specific prompts from a learnable prompt memory. The memory stores diverse, domain-discriminative prompt representations and is queried via domain features extracted from the Fourier spectrum. To learn robust and discriminative domain features, we introduce a novel Low-Frequency Feature Contrastive (LFC) learning framework that clusters representations from the same domain while separating those from different domains. Extensive experiments on two medical segmentation tasks demonstrate that APEX significantly improves generalization across both seen and unseen domains. Furthermore, it complements any existing backbones and consistently enhances performance, confirming its effectiveness as a plug-and-play prompting solution in medical fields. The code is available at https://github.com/cetinkayaevren/apex/

Increasingly advanced data augmentation techniques have greatly aided clinical medical research, increasing data diversity and improving model generalization capabilities. Although most current basic models exhibit strong generalization abilities, image quality varies due to differences in equipment and operators. To address these challenges, we present SegTTA, a framework that improves medical image segmentation without model retraining by combining four augmentations (Gamma correction, Contrast enhancement, Gaussian blur, Gaussian noise) with weighted voting across multiple MedSAM2 checkpoints. Experiments demonstrate consistent improvements across three diverse datasets: healthy uterus segmentation, uterine myoma detection, and multi class hepatic structure segmentation. Ablation studies reveal that large organs benefit from intensity augmentations while small lesions require noise augmentations. The voting threshold controls the coverage precision trade off, enabling task specific optimization for different clinical requirements. Ultimately, on a multiclass hepatic vessel dataset, compared to MedSAM2 baselines, our method achieves an increase of 1.6 in mIoU and 1.9 in aIoU, along with a reduction of approximately 2.0 in HD95. Code will be available at https://github.com/AIGeeksGroup/SegTTA.

Pancreatic ductal adenocarcinoma (PDAC) segmentation on contrast-enhanced CT is inherently ambiguous: inter-rater disagreement among experts reflects genuine uncertainty rather than annotation noise. Standard deep learning approaches assume a single ground truth, producing probabilistic outputs that can be poorly calibrated and difficult to interpret under such ambiguity. We present TwinTrack, a framework that addresses this gap through post-hoc calibration of ensemble segmentation probabilities to the empirical mean human response (MHR) -the fraction of expert annotators labeling a voxel as tumor. Calibrated probabilities are thus directly interpretable as the expected proportion of annotators assigning the tumor label, explicitly modeling inter-rater disagreement. The proposed post-hoc calibration procedure is simple and requires only a small multi-rater calibration set. It consistently improves calibration metrics over standard approaches when evaluated on the MICCAI 2025 CURVAS-PDACVI multi-rater benchmark.

Reliable uncertainty estimation is critical for medical image segmentation, where automated contours feed downstream quantification and clinical decision support. Many strong uncertainty methods require repeated inference, while efficient single-forward-pass alternatives often provide weaker failure ranking or rely on restrictive feature-space assumptions. We present $\textbf{SegWithU}$, a post-hoc framework that augments a frozen pretrained segmentation backbone with a lightweight uncertainty head. SegWithU taps intermediate backbone features and models uncertainty as perturbation energy in a compact probe space using rank-1 posterior probes. It produces two voxel-wise uncertainty maps: a calibration-oriented map for probability tempering and a ranking-oriented map for error detection and selective prediction. Across ACDC, BraTS2024, and LiTS, SegWithU is the strongest and most consistent single-forward-pass baseline, achieving AUROC/AURC of $0.9838/2.4885$, $0.9946/0.2660$, and $0.9925/0.8193$, respectively, while preserving segmentation quality. These results suggest that perturbation-based uncertainty modeling is an effective and practical route to reliability-aware medical segmentation. Source code is available at https://github.com/ProjectNeura/SegWithU.

Purpose: Adaptive skip modules can improve medical image segmentation, but searching for them is computationally costly. Implantable Adaptive Cells (IACs) are compact NAS modules inserted into U-Net skip connections, reducing the search space compared with full-network NAS. However, the original IAC framework still requires a 200-epoch differentiable search for each backbone and dataset. Methods: We analyzed the temporal behavior of operations and edges within IAC cells during differentiable search on public medical image segmentation benchmarks. We found that operations selected in the final discrete cell typically emerge among the strongest candidates early in training, and their architecture parameters stabilize well before the final epoch. Based on this, we propose a Jensen--Shannon-divergence-based stability criterion that tracks per-edge operation-importance distributions and progressively prunes low-importance operations during search. The accelerated framework is called IAC-LTH. Results: Across four public benchmarks (ACDC, BraTS, KiTS, AMOS), several 2-D U-Net backbones, and a 2-D nnU-Net pipeline, IAC-LTH discovers IAC cells whose patient-level segmentation performance matches and sometimes slightly exceeds that of cells found by the original full-length search, while reducing wall-clock NAS cost by 3.7x to 16x across datasets and backbones. These results are consistent across architectures, benchmarks, and both non-augmented and augmented training settings, while preserving the gains of IAC-equipped U-Nets over strong attention-based and dense-skip baselines. Conclusion: Competitive IAC architectures can be identified from early-stabilizing operations without running the full search, making adaptive skip-module design more practical for medical image segmentation under realistic computational constraints.

Myotubes are multinucleated muscle fibers serving as key model systems for studying muscle physiology, disease mechanisms, and drug responses. Mechanistic studies and drug screening thereby rely on quantitative morphological readouts such as diameter, length, and branching degree, which in turn require precise three-dimensional instance segmentation. Yet established pretrained biomedical segmentation models fail to generalize to this domain due to the absence of large annotated myotube datasets. We introduce a geometry-driven synthesis pipeline that models individual myotubes via polynomial centerlines, locally varying radii, branching structures, and ellipsoidal end caps derived from real microscopy observations. Synthetic volumes are rendered with realistic noise, optical artifacts, and CycleGAN-based Domain Adaptation (DA). A compact 3D U-Net with self-supervised encoder pretraining, trained exclusively on synthetic data, achieves a mean IPQ of 0.22 on real data, significantly outperforming three established zero-shot segmentation models, demonstrating that biophysics-driven synthesis enables effective instance segmentation in annotation-scarce biomedical domains.

Medical image segmentation (MIS) is a fundamental component of computer-assisted diagnosis and clinical decision support. Over the past decade, numerous architectures specifically tailored to medical imaging have emerged to address domain-specific challenges such as low contrast, small anatomical structures, and limited annotated data. In parallel, rapid progress in computer vision has produced highly capable general-purpose vision models (GP-VMs) originally designed for natural images. Despite their strong performance on standard vision benchmarks, their effectiveness for MIS remains insufficiently understood. In this controlled empirical study, we examine whether specialized medical segmentation architectures (SMAs) provide systematic advantages over modern GP-VMs for 2D MIS. We compare eleven SMAs and GP-VMs using a unified training and evaluation protocol across three heterogeneous datasets, each covering different 2D imaging modalities, class structures, and data characteristics. Beyond segmentation performance, we employ linear mixed-effects models (LMMs) for statistical assessment and qualitative Grad-CAM visualizations to investigate explainability (XAI)-related model behavior. Our results imply that, for the analyzed settings, GP-VMs achieve performance comparable to that of specialized MIS models. Moreover, XAI analyses indicate that GP-VMs are capable of identifying clinically relevant structures despite the absence of explicit domain-specific architectural priors. These findings suggest that GP-VMs can represent a viable alternative to domain-specific methods for 2D MIS, highlighting the importance of informed model selection. All code and resources are available at GitHub.

Medical image analysis depends on accurate segmentation and controllable synthesis, but both tasks face severe spatial imbalance: lesions occupy small regions against large backgrounds. We study adaptive spatial weighting as a task-level design principle and instantiate it in two adapters. LAW learns per-pixel loss weights for mask-conditioned diffusion by modulating a ratio prior with a feature-dependent delta map, with normalization, clamping, and Dice regularization for stability. ORDER improves lightweight segmentation by adding selective bidirectional skip attention with stage-wise confidence gating. On held-out diffusion test sets, LAW lowers FID from 158.13$\pm$0.15 to 108.43$\pm$0.71 on Polyps, from 144.13$\pm$0.31 to 89.51$\pm$0.96 on KiTS19, and from 139.22$\pm$0.38 to 112.58$\pm$0.68 on BRISC, while improving held-out mask-recovery Dice from 0.681$\pm$0.013 to 0.825$\pm$0.003 on Polyps. When the resulting images are added to nnUNet training, downstream Polyps mDice rises from 71.7$\pm$0.4 to 74.1$\pm$0.8. On the cleaned Polyps segmentation protocol, the reported ORDER configuration reaches 76.3$\pm$1.9 mDice and 67.2$\pm$2.0 mIoU at 42K parameters and 0.11 GFLOPs, versus 70.3$\pm$1.5 mDice and 59.9$\pm$1.7 mIoU for matched MK-UNet. On BRISC under the same training recipe, ORDER reaches 77.4$\pm$0.8 mDice and 68.1$\pm$0.7 mIoU. These results position adaptive spatial weighting as a practical design idea for both medical diffusion and efficient segmentation.

Ambiguous 3D medical image segmentation often involves boundaries where different expert delineations are non-identical yet clinically plausible. Modeling such inter-observer variability requires a careful balance between diversity and anatomical fidelity: deterministic models preserve coherent volumetric structures but collapse expert disagreement into a single mask, while stochastic generative models can produce diverse samples but may introduce disconnected components or slice-to-slice inconsistency when generating full 3D masks from unstructured noise. We propose Volumetric Directional Diffusion (VDD), a prior-anchored diffusion framework that shifts stochastic generation from full-mask synthesis to residual boundary exploration. VDD uses a coarse consensus prediction as an anatomical anchor and learns a directional diffusion process to generate plausible boundary variations around ambiguous regions while preserving stable volumetric topology. Experiments on three multi-rater datasets, including LIDC-IDRI, KiTS21, and ISBI 2015, show that VDD improves uncertainty distribution alignment while maintaining competitive segmentation accuracy and 3D structural consistency. These results suggest that prior-anchored residual diffusion can model clinically plausible expert disagreement without sacrificing anatomical fidelity.

Medical image segmentation is a cornerstone of computer-assisted diagnosis and treatment planning. While recent multimodal vision-language models have shown promise in enhancing semantic understanding through textual descriptions, their resilience in "in-the-wild" clinical settings-characterized by scarce annotations and hardware-induced image degradations-remains under-explored. We introduce BiCLIP (Bidirectional and Consistent Language-Image Processing), a framework engineered to bolster robustness in medical segmentation. BiCLIP features a bidirectional multimodal fusion mechanism that enables visual features to iteratively refine textual representations, ensuring superior semantic alignment. To further stabilize learning, we implement an augmentation consistency objective that regularizes intermediate representations against perturbed input views. Evaluation on the QaTa-COV19 and MosMedData+ benchmarks demonstrates that BiCLIP consistently surpasses state-of-the-art image-only and multimodal baselines. Notably, BiCLIP maintains high performance when trained on as little as 1% of labeled data and exhibits significant resistance to clinical artifacts, including motion blur and low-dose CT noise.

Purpose: Developing generalizable medical image segmentation models is challenging because imaging data are distributed across institutions and differ in modality and acquisition protocol. Federated learning (FL) enables collaborative training without centralizing raw medical images, but cross-modality domain shifts between computed tomography (CT) and magnetic resonance imaging (MRI) can substantially reduce model performance. This study investigates augmentation-driven cross-modality FL for abdominal organ and whole-heart segmentation. Methods: We evaluate convolution-based spatial augmentation, frequency-domain argumentation, domain-specific normalization, and global intensity nonlinear (GIN) augmentation for multimodal segmentation. Abdominal organ segmentation and whole-heart segmentation are first evaluated using a 2D U-Net framework. For whole-heart segmentation, we additionally perform native 3D experiments using a self-configuring nnU-Net architecture on the CARE-WHS 2026 dataset, enabling evaluation of whether the observed cross-modality FL behavior persists when moving from slice-based 2D segmentation to volumetric 3D segmentation. Results: GIN provides the most consistent cross-modality performance among the evaluated approaches in the original 2D experiments. For pancreas segmentation, the Dice similarity coefficient (DSC) improved from 0.073 to 0.437 when CT data were incorporated through federated cross-modality training. In 3D whole-heart segmentation, FedGIN improved mean DSC over FedAvg from 0.8696 to 0.8901 on the unseen CT center and from 0.7160 to 0.7956 on the unseen MRI center. Relative to centralized GIN training, FedGIN retained 92.4% of performance on unseen CT data and achieved comparable performance on unseen MRI data (0.7956 versus 0.7937).

Deep learning has substantially advanced medical image segmentation, yet achieving robust generalization across diverse imaging modalities and anatomical structures remains a major challenge. A key contributor to this limitation lies in how existing architectures, ranging from CNNs to Transformers and their hybrids, primarily encode spatial information while overlooking frequency-domain representations that capture rich structural and textural cues. Although recent studies have begun exploring spectral information at the feature level, supervision-level integration of frequency cues-crucial for fine-grained object localization-remains largely untapped. To this end, we propose Phi-SegNet, a CNN-based architecture that incorporates phase-aware information at both architectural and optimization levels. The network integrates Bi-Feature Mask Former (BFMF) modules that blend neighboring encoder features to reduce semantic gaps, and Reverse Fourier Attention (RFA) blocks that refine decoder outputs using phase-regularized features. A dedicated phase-aware loss aligns these features with structural priors, forming a closed feedback loop that emphasizes boundary precision. Evaluated on five public datasets spanning X-ray, US, histopathology, MRI, and colonoscopy, Phi-SegNet consistently achieved state-of-the-art performance, with an average relative improvement of 1.54+/-1.26% in IoU and 0.98+/-0.71% in F1-score over the next best-performing model. In cross-dataset generalization scenarios involving unseen datasets from the known domain, it also exhibits robust and superior performance, highlighting its adaptability and modality-agnostic design. These findings demonstrate the potential of leveraging spectral priors in both feature representation and supervision, paving the way for generalized segmentation frameworks that excel in fine-grained object localization. Our code is available on GitHub.

Accurate segmentation of anatomical structures in medical images is essential for diagnosis and treatment planning. While recent interactive segmentation foundation models enhance generalization through large-scale multimodal pretraining, they still depend on precise prompts and can fail in underrepresented clinical contexts (e.g., small organs-at-risk). We present AtlasSegFM, an atlas-guided framework that customizes off-the-shelf foundation models to new clinical contexts with a single annotated example. AtlasSegFM 1) performs atlas-query registration to generate context-aware prompts, 2) refines the segmentation with a frozen foundation model, and 3) applies a lightweight adaptive fusion module to combine atlas priors with foundation-model inputs and predictions. Extensive experiments on six public and in-house datasets across radiotherapy and vascular scenarios show consistent gains, with the largest improvements on small and delicate structures. AtlasSegFM provides a lightweight, deployable solution for one-shot customization of segmentation foundation models in real-world clinical workflows.

Recent medical MLLMs have made significant progress in generating step-by-step textual reasoning chains. However, they still struggle with complex clinical tasks that necessitate dynamic and iterative focusing on fine-grained visual regions. To close this gap, we introduce Ophiuchus, a versatile, tool-augmented framework that equips an MLLM to (i) decide when fine-grained visual evidence is needed, (ii) determine where to probe and ground within the medical image, and (iii) seamlessly weave the relevant sub-image content back into an interleaved, multimodal chain of thought for precise segmentation and diagnosis. Ophiuchus moves beyond mere tool-calling by tightly fusing the MLLM's inherent grounding and reasoning capabilities with external tools, enabling more accurate and trustworthy decisions. The core of our method is a three-stage training strategy: cold-start SFT for basic tool selection; self-reflection fine-tuning to strengthen decision revision; and agentic tool reinforcement learning to elicit sophisticated, expert-like diagnostic behaviors. Extensive experiments show that Ophiuchus consistently outperforms both closed-source and open-source SOTA methods across diverse medical benchmarks, including VQA, detection, and reasoning-based segmentation. Our project code is available at https://github.com/SII-zyj/Ophiuchus.

Generative models have achieved remarkable progress with the emergence of flow matching (FM). It has demonstrated strong generative capabilities and attracted significant attention as a simulation-free flow-based framework capable of learning exact data densities. Motivated by these advances, we propose LatentFM, a flow-based model operating in the latent space for medical image segmentation. To model the data distribution, we first design two variational autoencoders (VAEs) to encode both medical images and their corresponding masks into a lower-dimensional latent space. We then estimate a conditional velocity field that guides the flow based on the input image. By sampling multiple latent representations, our method synthesizes diverse segmentation outputs whose pixel-wise variance reliably captures the underlying data distribution, enabling both highly accurate and uncertainty-aware predictions. Furthermore, we generate confidence maps that quantify the model certainty, providing clinicians with richer information for deeper analysis. We conduct experiments on two datasets, ISIC-2018 and CVC-Clinic, and compare our method with several prior baselines, including both deterministic and generative approach models. Through comprehensive evaluations, both qualitative and quantitative results show that our approach achieves superior segmentation accuracy while remaining highly efficient in the latent space.

Medical image segmentation is crucial for clinical diagnosis and treatment planning. Traditional methods typically produce a single segmentation mask, failing to capture inherent uncertainty. Recent generative models enable the creation of multiple plausible masks per image, mimicking the collaborative interpretation of several clinicians. However, these approaches remain computationally heavy. We propose MedSegLatDiff, a diffusion based framework that combines a variational autoencoder (VAE) with a latent diffusion model for efficient medical image segmentation. The VAE compresses the input into a low dimensional latent space, reducing noise and accelerating training, while the diffusion process operates directly in this compact representation. We further replace the conventional MSE loss with weighted cross entropy in the VAE mask reconstruction path to better preserve tiny structures such as small nodules. MedSegLatDiff is evaluated on ISIC-2018 (skin lesions), CVC-Clinic (polyps), and LIDC-IDRI (lung nodules). It achieves state of the art or highly competitive Dice and IoU scores while simultaneously generating diverse segmentation hypotheses and confidence maps. This provides enhanced interpretability and reliability compared to deterministic baselines, making the model particularly suitable for clinical deployment.

Despite notable progress in text-guided medical image segmentation nowadays, these methods are limited to single-round dialogues and fail to support multi-round reasoning, which is important for medical education scenarios. In this work, we introduce Multi-Round Entity-Level Medical Reasoning Segmentation (MEMR-Seg), a new task that requires generating segmentation masks through multi-round queries with entity-level reasoning, helping learners progressively develop their understanding of medical knowledge. To support this task, we construct MR-MedSeg, a large-scale dataset of 177K multi-round medical segmentation dialogues, featuring entity-based reasoning across rounds. Furthermore, we propose MediRound, an effective baseline model designed for multi-round medical reasoning segmentation. To mitigate the inherent error propagation within the chain-like pipeline of multi-round segmentation, we introduce a lightweight yet effective Judgment & Correction Mechanism during model inference. Experimental results demonstrate that our method effectively addresses the MEMR-Seg task and outperforms conventional medical referring segmentation methods. The project is available at https://github.com/Edisonhimself/MediRound.

Robust medical image segmentation across modalities remains challenging due to severe domain shifts and the lack of target-domain labels. While diffusion models have been explored for cross-domain generation and augmentation, target-domain conditional diffusion training typically relies on highly noisy pseudo masks; naively conditioning on a single Arg-Max pseudo-label can corrupt diffusion training and downstream segmentation. We propose UPDiff-UDA, a unified UDA framework whose core is an uncertainty-guided training objective for target-domain conditional diffusion. Given an imperfect source-trained segmenter, we use its per-pixel softmax distribution to form ranked pseudo-label maps (Arg-Max, Arg-2nd, Arg-3rd, ...). Each map yields a conditional score estimate, and we aggregate them via pixel-wise confidence weighting to obtain an uncertainty-reweighted score for score matching, improving robustness to pseudo-label noise while leveraging alternative plausible labels in uncertain regions. We further provide a theoretical justification showing that confidence-weighted aggregation follows a minimum-MSE convex-combination principle under the segmenter-induced surrogate label distribution. To improve pseudo-condition quality, we also introduce a feature-guided, low-degree-of-freedom Bézier curve adaptation to reduce appearance gaps. Experiments on multiple public datasets and modality shifts show that UPDiff-UDA generates high-fidelity labeled target-style samples for augmentation and consistently outperforms strong UDA baselines. The code for this project is available at: https://github.com/superlc1995/Multi-Channel-Uncertainty-Diffusion-UDA

Lightweight 3D medical image segmentation remains constrained by a fundamental \textit{efficiency / robustness conflict''}, particularly when processing complex anatomical structures and heterogeneous modalities. In this paper, we study how to redesign the framework based on the characteristics of high-dimensional 3D images, and explore data synergy to overcome the fragile representation of lightweight methods. Our approach, VeloxSeg, begins with a deployable and extensible dual-stream CNN-Transformer architecture composed of Paired Window Attention (PWA) and Johnson-Lindenstrauss lemma-guided convolution (JLC). For each 3D image, we invoke a glance-and-focus'' principle, where PWA rapidly retrieves multi-scale information, and JLC ensures robust local feature extraction with minimal parameters, significantly enhancing the model's ability to operate with low computational budget. Followed by an extension of the dual-stream architecture that incorporates modal interaction into the multi-scale image-retrieval process, VeloxSeg efficiently models heterogeneous modalities. Finally, Spatially Decoupled Knowledge Transfer (SDKT) via Gram matrices injects the texture prior extracted by a self-supervised network into the segmentation network, yielding stronger representations than baselines at no extra inference cost. Experimental results on multimodal benchmarks show that VeloxSeg achieves a 26% Dice improvement, alongside increasing GPU throughput by 11$\times$, CPU by 48$\times$, and reducing training peak GPU memory usage by $1/20$, inference by $1/24$. Code is available at https://github.com/JinPLu/VeloxSeg.

Supervised deep learning achieves strong performance in biomedical image segmentation but relies on costly pixel-wise annotations, motivating semi-supervised approaches that exploit unlabeled data. We introduce a diffusion-based teacher--student framework in which segmentation predictions are used to condition image denoising, encouraging the production of more informative pseudo-labels. The teacher is first pretrained through an unsupervised reconstruction task using diffusion-style corruption, timestep conditioning, and denoising. Starting from a corrupted empty mask, the model predicts an intermediate segmentation that conditions image denoising, encouraging the predicted mask to capture structural information useful for recovering the original image. The resulting teacher is then co-trained with a student using supervised segmentation on labeled samples and cross pseudo-supervision on unlabeled data. We further introduce a multi-round extension during co-training, in which the teacher generates multiple stochastic image reconstructions and corresponding segmentation predictions, providing additional reconstruction and alignment signals to improve its pseudo-labels. We evaluate the proposed framework on three public 2D biomedical segmentation datasets and a 3D left atrial segmentation benchmark. Across several labeling regimes, our method achieves competitive or superior performance compared with state-of-the-art semi-supervised approaches, with the largest gains observed under severe label scarcity.