Foundation models for image segmentation have shown strong generalization in natural images, yet their applicability to 3D medical imaging remains limited. In this work, we study the zero-shot use of Segment Anything Model 2 (SAM2) for automatic segmentation of volumetric CT data, without any fine-tuning or domain-specific training. We analyze how SAM2 should be applied to CT volumes and identify its main limitation: the lack of inherent volumetric awareness. To address this, we propose a set of inference-alone architectural and procedural modifications that adapt SAM2's video-based memory mechanism to 3D data by treating CT slices as ordered sequences. We conduct a systematic ablation study on a subset of 500 CT scans from the TotalSegmentator dataset to evaluate prompt strategies, memory propagation schemes and multi-pass refinement. Based on these findings, we select the best-performing configuration and report final results on a bigger sample of the TotalSegmentator dataset comprising 2,500 CT scans. Our results show that, even with frozen weights, SAM2 can produce coherent 3D segmentations when its inference pipeline is carefully structured, demonstrating the feasibility of a fully zero-shot approach for volumetric medical image segmentation.
Diffusion models have become a leading approach for high-fidelity medical image synthesis. However, most existing methods for 3D medical image generation rely on convolutional U-Net backbones within latent diffusion frameworks. While effective, these architectures impose strong locality biases and limited receptive fields, which may constrain scalability, global context integration, and flexible conditioning. In this work, we introduce VolDiT, the first purely transformer-based 3D Diffusion Transformer for volumetric medical image synthesis. Our approach extends diffusion transformers to native 3D data through volumetric patch embeddings and global self-attention operating directly over 3D tokens. To enable structured control, we propose a timestep-gated control adapter that maps segmentation masks into learnable control tokens that modulate transformer layers during denoising. This token-level conditioning mechanism allows precise spatial guidance while preserving the modeling advantages of transformer architectures. We evaluate our model on high-resolution 3D medical image synthesis tasks and compare it to state-of-the-art 3D latent diffusion models based on U-Nets. Results demonstrate improved global coherence, superior generative fidelity, and enhanced controllability. Our findings suggest that fully transformerbased diffusion models provide a flexible foundation for volumetric medical image synthesis. The code and models trained on public data are available at https://github.com/Cardio-AI/voldit.
Deep learning and generative models are advancing rapidly, with synthetic data increasingly being integrated into training pipelines for downstream analysis tasks. However, in medical imaging, their adoption remains constrained by the scarcity of reliable annotated datasets. To address this limitation, we propose 3D-LLDM, a label-guided 3D latent diffusion model that generates high-quality synthetic magnetic resonance (MR) volumes with corresponding anatomical segmentation masks. Our approach uses hepatobiliary phase MR images enhanced with the Gd-EOB-DTPA contrast agent to derive structural masks for the liver, portal vein, hepatic vein, and hepatocellular carcinoma, which then guide volumetric synthesis through a ControlNet-based architecture. Trained on 720 real clinical hepatobiliary phase MR scans from Samsung Medical Center, 3D-LLDM achieves a Fréchet Inception Distance (FID) of 28.31, improving over GANs by 70.9% and over state-of-the-art diffusion baselines by 26.7%. When used for data augmentation, the synthetic volumes improve hepatocellular carcinoma segmentation by up to 11.153% Dice score across five CNN architectures.
The advent of Transformer and Mamba-based architectures has significantly advanced 3D medical image segmentation by enabling global contextual modeling, a capability traditionally limited in Convolutional Neural Networks (CNNs). However, state-of-the-art Transformer models often entail substantial computational complexity and parameter counts, which is particularly prohibitive for volumetric data and further exacerbated by the limited availability of annotated medical imaging datasets. To address these limitations, this work introduces SegMaFormer, a lightweight hybrid architecture that synergizes Mamba and Transformer modules within a hierarchical volumetric encoder for efficient long-range dependency modeling. The model strategically employs Mamba-based layers in early, high-resolution stages to reduce computational overhead while capturing essential spatial context, and reserves self-attention mechanisms for later, lower-resolution stages to refine feature representation. This design is augmented with generalized rotary position embeddings to enhance spatial awareness. Despite its compact structure, SegMaFormer achieves competitive performance on three public benchmarks (Synapse, BraTS, and ACDC), matching the Dice coefficient of significantly larger models. Empirically, our approach reduces parameters by up to 75x and substantially decreases FLOPs compared to current state-of-the-art models, establishing an efficient and high-performing solution for 3D medical image segmentation.
Radiotherapy workflows for oncological patients increasingly rely on multi-modal medical imaging, commonly involving both Magnetic Resonance Imaging (MRI) and Computed Tomography (CT). MRI-only treatment planning has emerged as an attractive alternative, as it reduces patient exposure to ionizing radiation and avoids errors introduced by inter-modality registration. While nnU-Net-based frameworks are predominantly used for MRI-to-CT synthesis, we explore Mamba-based architectures for this task, aiming to showcase the advantages of state-space modeling for cross-modality translation compared to standard convolutional neural networks. Specifically, we adapt both the U-Mamba and the SegMamba architecture, originally proposed for segmentation, to perform cross-modality image generation. Our 3D Mamba architecture effectively captures complex volumetric features and long-range dependencies, thus allowing accurate CT synthesis while maintaining fast inference times. Experiments were conducted on a subset of SynthRAD2025 dataset, comprising registered single-channel MRI-CT volume pairs across three anatomical regions. Quantitative evaluation is performed via a combination of image similarity metrics computed in Hounsefield Units (HU) and segmentation-based metrics obtained from TotalSegmentator to ensure geometric consistency is preserved. The findings pave the way for the integration of state-space models into radiotherapy workflows.
The Brain Tumor Reporting and Data System (BT-RADS) standardizes post-treatment MRI response assessment in patients with diffuse gliomas but requires complex integration of imaging trends, medication effects, and radiation timing. This study evaluates an end-to-end multi-agent large language model (LLM) and convolutional neural network (CNN) system for automated BT-RADS classification. A multi-agent LLM system combined with automated CNN-based tumor segmentation was retrospectively evaluated on 509 consecutive post-treatment glioma MRI examinations from a single high-volume center. An extractor agent identified clinical variables (steroid status, bevacizumab status, radiation date) from unstructured clinical notes, while a scorer agent applied BT-RADS decision logic integrating extracted variables with volumetric measurements. Expert reference standard classifications were established by an independent board-certified neuroradiologist. Of 509 examinations, 492 met inclusion criteria. The system achieved 374/492 (76.0%; 95% CI, 72.1%-79.6%) accuracy versus 283/492 (57.5%; 95% CI, 53.1%-61.8%) for initial clinical assessments (+18.5 percentage points; P<.001). Context-dependent categories showed high sensitivity (BT-1b 100%, BT-1a 92.7%, BT-3a 87.5%), while threshold-dependent categories showed moderate sensitivity (BT-3c 74.8%, BT-2 69.2%, BT-4 69.3%, BT-3b 57.1%). For BT-4, positive predictive value was 92.9%. The multi-agent LLM system achieved higher BT-RADS classification agreement with expert reference standard compared to initial clinical scoring, with high accuracy for context-dependent scores and high positive predictive value for BT-4 detection.
We present the first study of Hyper-Connections (HC) for volumetric multi-modal brain tumor segmentation, integrating them as a drop-in replacement for fixed residual connections across five architectures: nnU-Net, SwinUNETR, VT-UNet, U-Net, and U-Netpp. Dynamic HC consistently improves all 3D models on the BraTS 2021 dataset, yielding up to +1.03 percent mean Dice gain with negligible parameter overhead. Gains are most pronounced in the Enhancing Tumor sub-region, reflecting improved fine-grained boundary delineation. Modality ablation further reveals that HC-equipped models develop sharper sensitivity toward clinically dominant sequences, specifically T1ce for Tumor Core and Enhancing Tumor, and FLAIR for Whole Tumor, a behavior absent in fixed-connection baselines and consistent across all architectures. In 2D settings, improvements are smaller and configuration-sensitive, suggesting that volumetric spatial context amplifies the benefit of adaptive aggregation. These results establish HC as a simple, efficient, and broadly applicable mechanism for multi-modal feature fusion in medical image segmentation.
Accurate multi-organ segmentation in abdominal CT scans is essential for computer-aided diagnosis and treatment. While convolutional neural networks (CNNs) have long been the standard approach in medical image segmentation, transformer-based architectures have recently gained attention due to their ability to model long-range dependencies. In this study, we systematically benchmark the three hybrid transformer-based models UNETR, SwinUNETR, and UNETR++ against a strong CNN baseline, SegResNet, for volumetric multi-organ segmentation on the heterogeneous RATIC dataset. The dataset comprises 206 annotated CT scans from 23 institutions worldwide, covering five abdominal organs. All models were trained and evaluated under identical preprocessing and training conditions using the Dice Similarity Coefficient (DSC) as the primary metric. The results show that the CNN-based SegResNet achieves the highest overall performance, outperforming all hybrid transformer-based models across all organs. Among the transformer-based approaches, UNETR++ delivers the most competitive results, while UNETR demonstrates notably faster convergence with fewer training iterations. These findings suggest that, for small- to medium-sized heterogeneous datasets, well-optimized CNN architectures remain highly competitive and may outperform hybrid transformer-based designs.
Equivocal 3D lesion segmentation exhibits high inter-observer variability. Conventional deterministic models ignore this aleatoric uncertainty, producing over-confident masks that obscure clinical risks. Conversely, while generative methods (e.g., standard diffusion) capture sample diversity, recovering complex topology from pure noise frequently leads to severe structural fractures and out-of-distribution anatomical hallucinations. To resolve this fidelity-diversity trade-off, we propose Volumetric Directional Diffusion (VDD). Unlike standard diffusion models that denoise isotropic Gaussian noise, VDD mathematically anchors the generative trajectory to a deterministic consensus prior. By restricting the generative search space to iteratively predict a 3D boundary residual field, VDD accurately explores the fine-grained geometric variations inherent in expert disagreements without risking topological collapse. Extensive validation on three multi-rater datasets (LIDC-IDRI, KiTS21, and ISBI 2015) demonstrates that VDD achieves state-of-the-art uncertainty quantification (significantly improving GED and CI) while remaining highly competitive in segmentation accuracy against deterministic upper bounds. Ultimately, VDD provides clinicians with anatomically coherent uncertainty maps, enabling safer decision-making and mitigating risks in downstream tasks (e.g., radiotherapy planning or surgical margin assessment).
Automated analysis of articulated bodies is crucial in medical imaging. Existing surface-based models often ignore internal volumetric structures and rely on deformation methods that lack anatomical consistency guarantees. To address this problem, we introduce a differentiable volumetric body model based on the Skinned Multi-Person Linear (SMPL) formulation, driven by a new Kinematic Tree-based Log-Euclidean PolyRigid (KTPolyRigid) transform. KTPolyRigid resolves Lie algebra ambiguities associated with large, non-local articulated motions, and encourages smooth, bijective volumetric mappings. Evaluated on 53 fetal MRI volumes, KTPolyRigid yields deformation fields with significantly fewer folding artifacts. Furthermore, our framework enables robust groupwise image registration and a label-efficient, template-based segmentation of fetal organs. It provides a robust foundation for standardized volumetric analysis of articulated bodies in medical imaging.