Medical Image Generation

Data scarcity in multimodal pathology motivates unified generative models that synthesize modality-specific appearance while preserving anatomically coherent structure. Although modalities differ in appearance statistics, morphological structures such as cellular topology and tissue boundaries are largely preserved across acquisition protocols. However, existing methods often model these factors within a homogeneous token stream, implicitly coupling structure with appearance and weakening structural controllability under modality shifts. To address this, we propose pathology Autorgressive modeling (PathAR), a structure-first autoregressive synthesis framework that explicitly factorizes structure and appearance for modality-label-conditioned pathology generation.PathAR employs a dual vector quantization (Dual-VQ) tokenizer to decompose samples into mask-grounded structure and appearance tokens, and an interleaved autoregressive (IAR) transformer with asymmetric attention visibility to enforce structure-to-appearance dependence. PathAR stabilizes morphology under heterogeneous modality-specific appearances and enables spatially aligned image--mask pair generation. Extensive experiments show that PathAR improves structural consistency and modality fidelity over baselines, maintains sample diversity, supports downstream segmentation in data-scarce regimes, and demonstrates extensibility to finer-grained intra-modality organ-label variation.

Generative models for volumetric medical images have found many applications in medical imaging, ranging from data augmentation to serving as priors for inverse problems. For these applications, generating high-resolution 3D images with strong controllability is essential but remains highly challenging. Existing approaches typically control generation either through radiology reports used as text prompts or through full image segmentation. While text-based prompting is flexible, it provides limited spatial control over the location, shape, and boundary of abnormalities. In contrast, segmentation-based methods receive precise spatial guidance but are restrictive in requiring full-organ annotations. In this work, we propose a flexible multimodal framework for controllable volumetric image generation that supports input from radiology reports and segmentation prompts (both optional). Our approach allows users to provide segmentation of a specific anatomy or abnormality without requiring full-organ annotations. The semantic meaning of the segmentation mask is specified through an accompanying text description, resulting in a highly flexible and scalable conditioning mechanism. We develop a memory-efficient architecture based on a modified diffusion transformer that jointly processes image and segmentation tokens. The model further incorporates gated attention to effectively attend to long radiology reports. Experiments demonstrate that our method achieves state-of-the-art perceptual and semantic scores (e.g., 24% relative improvement in mean FID), generates high-resolution anatomically consistent CT volumes, and improves data efficiency when used for data augmentation. Radiologists' evaluation further confirms strong alignment between generated and real medical images.

Multimodal MRI provides complementary information for neuroimaging analysis, where different imaging modalities capture distinct anatomical, tissue, and pathological features that support the development and evaluation of downstream AI applications. Although large-scale structural MRI resources are increasingly available, their modality coverage is often uneven across public and pooled neuroimaging datasets. This uneven modality coverage is further complicated by heterogeneity across sites, scanners, and acquisition protocols, as well as demographic and clinical variables that are often sparse, inconsistently recorded, or unavailable across studies. Synthetic MRI generation can help address this imbalance by synthesizing target-modality volumes for dataset augmentation and controlled synthetic cohort creation. However, many existing MRI synthesis approaches are trained on narrow modality sets or relatively homogeneous cohorts, limiting their applicability to large pooled neuroimaging resources where modality availability, acquisition protocols, and metadata coverage vary substantially across datasets. Diffusion models have become an attractive approach for MRI synthesis because of their strong sample fidelity and diversity, but sampling directly in 3D voxel space is computationally expensive and slow at inference. Latent diffusion improves practicality by synthesizing MRI in a learned, 3D latent space, although generation quality depends on the autoencoder's reconstruction fidelity and the resulting latent distribution. Our approach combines a Wavelet-Fusion variational autoencoder (WF-VAE) latent compressor with a conditional 3D U-Net diffusion model trained in the learned latent space using explicit modality and metadata conditioning. Our proposed Wavelet-Fusion Diffusion Model (WFDM) achieved the strongest distributional alignment among the evaluated synthetic MRI generators.

Modern 3D medical vision-language models (VLMs) can generate fluent radiology-style text while exhibit critically low pathology detection and output diversity, collapsing to generic templates that under-report rare yet critical findings. We identify this failure mode as Template Collapse. This failure stems from the unique constraints of 3D medical imaging, e.g., limited data, severe label imbalance, and weak signals from volumetric encoders. Under these constraints, text-generation objectives encourage shortcut learning and fluent but weakly grounded reports. We systematically diagnose the Template Collapse through clinical fidelity, output diversity, normal-template bias, and rare-finding survival. To mitigate it, we propose CLarGen, a decoupled framework that separates what to say (clinical detection) from how to say it (language synthesis). CLarGen uses (i) a Latent Query Transformer for multi-label pathology detection, (ii) pathology-guided retrieval for clinically matched exemplars, and (iii) a medical language model to synthesize the final report from detected findings and retrieved context. Across state-of-the-art 3D CT report generation baselines, CLarGen mitigates Template Collapse and substantially improves clinical accuracy (macro-F1 0.487 vs. 0.189; CRG 0.472 vs. 0.368) while maintaining fluent reporting. Our results suggest that explicit, measurable clinical grounding is essential for template-collapse-resistant 3D CT report generation. Code is available at https://github.com/ai-med/CLarGen.

Variational autoencoders (VAEs) compress high resolution CT volumes into compact latents while preserving clinically relevant structure. However, training CT-specific VAEs from scratch or heavily fine-tuning them incurs substantial computational and engineering cost, and often degrades under heterogeneous scanners, protocols, and diseases. This paper makes a progressive stride toward training-free medical VAEs by leveraging a critical observation: a single Foundation VAE, pretrained at scale on natural images and videos, can serve as a unified interface for CT Reconstruction, Augmentation, and Generation. With both encoder and decoder frozen, the Foundation VAE reconstructs CT volumes with preserved anatomy while suppressing acquisition noise; training segmentation models on these reconstructions improves surface accuracy by 3.9% NSD on average for pancreatic tumor and lung tumor. Within the same Foundation VAE latent space, a conditional latent diffusion model achieves 3.9% lower average FVD with 36.2% higher CT CLIP score, and improves multi-disease generation faithfulness across 18 types by 2.76% AUC. These results demonstrate Foundation VAEs as a practical interface for scalable CT representation reuse and faithful CT generation. Our code and demo are available at https://github.com/qic999/Foundation-VAE.

While automated diagnosis systems have achieved remarkable success in computed tomography (CT)-based lung cancer screening, their development remains limited by the scarcity of diverse, annotated pulmonary nodule datasets. Diffusion-based generative models offer a promising strategy for data synthesis; however, many existing conditional approaches primarily optimize spatial reconstruction losses, which encourage voxel-wise similarity but may inadequately constrain lesion-level intensity distributions. As a result, these methods may produce over-smoothed texture profiles and underrepresent the distinct attenuation characteristics of different nodule subtypes, including solid, part-solid, and ground-glass nodules. To address this challenge, we propose a controllable latent diffusion model that synthesizes pulmonary nodules within full 3D CT volumes while accurately modeling nodule-specific intensity distributions. Specifically, rather than relying solely on spatial losses, we introduce a histogram-based regularization term that constrains voxel intensity distributions during the generative process. The model combines subtype, spatial mask, and Hounsfield unit (HU) histogram conditioning with the differentiable feature-space histogram regularization term to better align lesion-level intensity distributions, improving the visual plausibility and subtype consistency of synthesized nodules. Extensive experiments on lung CT data demonstrate that our framework achieves strong visual realism, validated through both quantitative metrics and a visual Turing test. Furthermore, when used for data augmentation, the generated nodules improve performance in downstream clinical tasks, particularly for underrepresented nodule subtypes, and show a potential benefit for subtype-informed malignancy classification.

Synthesizing high fidelity contrast enhanced MRI is clinically valuable for safer and more efficient breast cancer screening, yet remains challenging due to complex lesion textures and heterogeneous enhancement patterns.

The major limitations of gastrointestinal (GI) endoscopy AI systems arise from a shortage of annotated data, strict privacy policies, and significant bottlenecks in conventional model fine-tuning. Such limitations impede the successful application of sophisticated AI models in clinical practice, particularly affecting the reliability and scalability of diagnosis. In this paper, we present a dual-pipeline PEFT model that addresses two fundamental problems: medical Visual Question Answering (VQA) and the generation of privacy-preserving synthetic data. For clinical VQA, we adopt the Florence-2 vision-language model. Leveraging PEFT enhances model interpretability while substantially reducing the computational cost of training. Simultaneously, we employ Low-Rank Adaptation (LoRA) with Stable Diffusion 2.1 to generate high-quality GI images that enhance training databases without violating patient privacy. This research utilized the Kvasir-VQA dataset. Our Florence-2 VQA model achieved ROUGE-1 of 0.92, ROUGE-L of 0.91, and BLEU score improvements from 0.08 to 0.24. Fine-tuning on private datasets consistently showed better results than fine-tuning on public datasets. The rank-4 LoRA synthesis achieved optimal performance with a fidelity score of 0.290, an agreement score of 0.730, and a Frechet BiomedCLIP Distance (FBD) of 1450, reducing computational costs by almost 90 percent. This framework improves the clinical potential of AI in GI endoscopy. Compared to FLUX, MSDM, and Kandinsky 2.2, our model demonstrates superior FBD and strong semantic alignment. While other models lead in Fidelity or Agreement, our lower FBD indicates better image-text coherence. These results establish our approach as a robust solution for enhancing VQA and synthetic data generation in clinical AI.

Ultra-low-field (ULF) MRI offers portable and accessible neuroimaging but suffers from reduced signal-to-noise ratio and limited spatial resolution compared to high-field (HF) systems. Acquiring paired ULF-HF data for supervised enhancement is often difficult, particularly in resource-limited settings. We introduce ULF-Synth, a framework that combines: (i) acquisition-based synthesis of realistic ULF images from HF volumes to create large-scale paired training data, (ii) a spatial-frequency domain objective that prioritizes recovery of high-frequency anatomical detail. This formulation is architecture-agnostic, consistently improving structural similarity and perceptual fidelity across encoder-decoder, adversarial, and diffusion-based translation models. When trained exclusively on synthetic data, the resulting models generalize effectively to real 64mT ULF acquisitions, improving downstream multiclass brain segmentation and achieving higher radiologist preference and diagnostic acceptability in a blinded reader study. These findings demonstrate that synthetic paired supervision provides a practical and scalable pathway for enhancing ULF MRI without requiring real paired acquisitions. Code, Models and Dataset: https://github.com/toufiqmusah/ULF-Synth

CT report generation (CTRG) requires models to summarize three-dimensional anatomical context and pathological findings from hundreds of axial slices. Existing methods typically learn a direct image-to-text mapping, providing limited mechanisms for modeling how CT evidence evolves across slices or how reports respond to controlled changes in latent lesion-related factors. We propose SliceWorld, a CT-specific world-state framework that treats an axial CT scan as an ordered sequence along the z-axis. SliceWorld encodes prefix CT evidence into factor-aware latent states containing anatomy, lesion, and uncertainty components, and projects these states into world tokens used for multi-step future-slice feature prediction, lesion-factor intervention, and LLM-based report generation. The model is first pretrained on CT slice sequences with predictive, factor-aware, and counterfactual objectives, and is then fine-tuned on paired CT-report data. Experiments on M3D-Cap and CT-RATE show that SliceWorld improves natural language generation metrics and clinically oriented automatic evaluation. Further analyses demonstrate multi-horizon future-slice prediction, measurable factor alignment, reduced-slice robustness, and selective lesion-sensitive report modulation.

Generative augmentation is often proposed as a remedy for small medical-image datasets, but synthetic images are only useful when they improve downstream task performance. "Augmentation" here means synthetic supplementation: GAN-generated samples added to the real training pool, not geometric or photometric transforms of existing images. Twelve class-plane StyleGAN2-ADA generators were trained on constrained BRISC 2025 partitions to test whether their output, with or without InceptionV3 feature-space filtering, improves held-out tumour classification across three classifier families: a random forest (RF) on InceptionV3 features, a compact two-headed convolutional neural network (CNN), and MobileViTV2, a mobile hybrid convolutional-transformer. Each was evaluated at 1:1 and 1:2 real-to-synthetic ratios. An independent GPT-5.5 blind test placed gated real-versus-synthetic discrimination at 57.73% (95% CI: 54.48--60.92%) on the model-legible subset -- modestly above chance. The RF classifier did not benefit from the synthetic MRIs. The CNN showed consistent mean gains that did not survive Holm correction. MobileViTV2 showed the clearest benefit: filtered 1:1 augmentation improved tumour classification accuracy by 1.02% absolute (95% CI: 0.54--1.54%; Holm-corrected p = 0.0104). A secondary efficiency analysis found that every augmented CNN condition selected its checkpoint 42--64% earlier than baseline, while compute-matched MobileViTV2 runs reached selection after 50--67% fewer real-data epochs. Overall, augmentation utility was found to be architecture- and ratio-dependent, not guaranteed by visual fidelity alone.

Children with rare genetic diseases often exhibit distinctive facial phenotypes, yet developing computer vision systems for early diagnosis remains challenging due to extreme data scarcity, privacy constraints, and limited data sharing in pediatric settings. These challenges not only hinder automated diagnosis but also restrict the availability of visual resources for clinical genetic counseling. While prior work has shown that synthetic data can augment real datasets and preserve phenotype-level semantics, it remains unclear whether synthetic data alone is sufficient for learning in ultra-low-resource pediatric settings. In this work, we study the synthetic-only regime for pediatric rare disease recognition. Under a controlled experimental setup, models are trained exclusively on phenotype-aware synthetic facial images at increasing scales. We find that synthetic-only training achieves performance comparable to real-data-only baselines at sufficient scale across multiple backbones, suggesting that high-fidelity synthetic data can approximate clinically meaningful distributions. These findings together further enable the use of synthetic pediatric facial images as privacy-preserving resources for genetic education and counseling, supporting clinician training and patient communication. Our results highlight the potential of computer vision to improve data efficiency and expand accessible visual tools in children's healthcare.

The synergistic interpretation of anatomical information from computed tomography (CT) and metabolic information from positron emission tomography (PET) is important to oncologic imaging. However, existing deep learning methods for PET/CT remain largely task-specific, are often trained on single-center cohorts, or adopt dual-branch fusion schemes that delay cross-modal interaction and underutilize early spatial correspondence between PET and CT. To address these limitations, we present an open-source, multi-center, whole-body FDG PET/CT foundation model utilizing 4,997 harmonized scans from four public datasets. Our framework employs hierarchical UNet-shaped backbones with early channel-wise concatenation, enabling anatomical and metabolic features to interact from the first embedding layer onward. We further introduce a masked autoencoding objective based on zero-mean imputation, combined with a weighted global reconstruction loss. This design avoids non-physical intensity discontinuities at masked-region boundaries that arise from learnable mask tokens. On downstream AutoPET lesion segmentation, the proposed models demonstrate strong label efficiency: with only 10% of the labeled training data, they achieve performance comparable to models trained from scratch on the full dataset. Under extreme 5-shot linear probing, joint PET/CT pretraining also achieves higher Dice scores than separated-modality pretraining. This multi-center foundation model demonstrates label efficiency and cross-modality representation learning for PET/CT tumor segmentation. It provides a robust, open-source basis for advancing automated oncologic imaging, significantly reducing the need for large-scale manual annotations in clinical practice.

Synthetic PET images are valuable for quantitative imaging workflow development, scalable virtual imaging trials, and deep learning model training, but conventional physics-based simulation approaches are computationally intensive, limited in anatomical variability, and often fail to capture heterogeneous PET uptake. This study developed a pretrained domain-adapted diffusion (PAD) model for anatomy-conditioned PET synthesis from uniform organ activity maps. PAD adopts a natural-image pretrained text-to-image decoder with an upstream conditioning encoder and a downstream PET-domain adapter. A two-phase training strategy was used, with the first phase learning coarse uptake distributions and the second refining local image details. Uniform organ activity maps were generated from CT-based segmentations by assigning each organ its mean uptake from the paired PET image. Evaluation included quantitative accuracy, noise assessment, radiomic analysis, tumor segmentation performance, and a human observer study. PAD-generated images achieved high quantitative accuracy, with concordance correlation coefficients above 0.92 between organ mean SUVs and assigned activity values. The synthesized images showed noise levels and texture characteristics similar to target PET images and produced comparable tumor segmentation performance. In a two-alternative forced-choice observer study, four readers achieved approximately 50% accuracy, indicating visual indistinguishability between synthesized and target images. PAD also generated realistic PET images from XCAT-derived activity maps, demonstrating compatibility with phantom-based anatomical priors. Overall, PAD provides a diffusion-based framework for generating clinically relevant heterogeneous PET images from uniform organ activity maps derived from clinical segmentations or digital phantoms, supporting data augmentation and downstream imaging studies.

High-resolution 3D medical image generation remains challenging because fully volumetric models are computationally expensive, while efficient 2D slice generators often fail to preserve anatomical consistency across the third dimension. We propose LiFT, a framework for Lifted inter-slice Feature Trajectories that factorizes 3D volume synthesis into per-slice image generation and inter-slice trajectory learning. Rather than modeling the volumetric distribution end-to-end, LiFT treats a volume as an ordered trajectory in feature space, capturing how anatomical structures appear, transform, and disappear across depth. A tri-planar drifting loss aligns the trajectory of generated slices with the trajectories of real volumes, enabling distributional learning over inter-slice progressions in unconditional generation; in paired translation, a bidirectional $z$-context mixer trained against the registered target supplies through-plane coherence while preserving per-slice fidelity. We evaluate LiFT on BraTS 2023 (unconditional and missing-modality MR) and SynthRAD2023 (MR-to-CT). Across these settings, LiFT preserves per-slice quality, approaches the reported cWDM missing-MR reconstruction quality at \sim$$135\times lower inference cost (without formal equivalence testing), and improves through-plane coherence on MR-to-CT relative to a no-mapper ablation, demonstrating that lightweight inter-slice trajectory learning is a viable route to high-resolution 3D medical synthesis.

Rare diseases dominate the diagnostic challenge in medical imaging yet are severely underrepresented in clinical datasets, causing classifiers to fail on exactly the conditions where reliable detection matters most. Generative augmentation can supply the missing tail-class coverage, but coarse disease labels aggregate diverse subtypes and acquisition settings into multi-modal conditionals that bias generators toward dominant submodes, while a shared Gaussian source forces rare subpopulations through disproportionately long transport paths. We propose an offline strategy that introduces informative priors at two levels: first, we partition each coarse label into coherent submodes via Gaussian mixture modeling in the generative model's latent space; second, we learn subclass-conditioned source distributions that re-center and re-scale the starting distribution per submode, shortening trajectories and reducing within-subclass dispersion. To prevent degenerate solutions we impose explicit geometric control, moderately concentrating normalized displacement directions around learnable prototypes while capping path-length outliers. On long-tailed chest X-ray (MIMIC-LT, NIH-LT) and CT slice (CT-RATE) benchmarks the proposed method consistently improves tail-class generation fidelity and diversity (FID, IRS) and is a promising augmentation strategy that reliably improves downstream balanced accuracy and macro-F1 over a non-augmented baseline across modalities.

Medical image-to-image (I2I) translation enables virtual scanning, i.e. the synthesis of a target imaging modality from a source one without additional acquisitions. Despite growing interest, most proposed methods operate on 2D slices, are evaluated on isolated tasks with different experimental set-ups and lack clinical validation. The primary contribution of this work is a reproducible, standardized comparative evaluation of 3D I2I translation methods in oncological imaging, designed to standardize preprocessing, splitting, inference, and multi-level evaluation across heterogeneous clinical tasks. Within this framework, we compare seven generative models, three Generative Adversarial Networks (GANs: Pix2Pix, CycleGAN, SRGAN) and four latent generative models (Latent Diffusion Model, Latent Diffusion Model+ControlNet, Brownian Bridge, Flow Matching), across eleven datasets spanning three anatomical regions (head/neck, lung, pelvis) and four translation directions (cone-beam CT to CT, MRI to CT, CT to PET, MRI T2-weighted to T2-FLAIR), for a total of 77 experiments under uniform training, inference, and evaluation conditions. The results show that GANs outperform latent generative models across all tasks, with SRGAN achieving statistically significant superiority. Our lesion-level analysis reveals that all models struggle with small lesions and that, in CT to PET synthesis, models reproduce lesion shape more reliably than absolute uptake-related intensity. We also performed a Visual Turing test administered to 17 physicians, including 15 radiologists, which shows near-chance classification accuracy (56.7%), confirming that synthetic volumes are largely indistinguishable from real acquisitions, while exposing a dissociation between quantitative metrics and clinical preference.

Radiation therapy (RT) requires precise dose delivery over multiple fractions, with CT fundamental for treatment planning due to its electron density information. Repeated CT acquisitions impose radiation exposure and logistical burdens, MRI lacks electron density, and cone-beam CT (CBCT) requires correction for dose calculation. Synthetic CT (sCT) generation addresses these by converting MRI or CBCT into CT-equivalent images with accurate Hounsfield Unit (HU) values, enabling MRI-only RT and CBCT-based adaptive workflows. Building on SynthRAD2023, SynthRAD2025 benchmarked sCT methods on 2,362 patients from five European centers across head and neck, thorax, and abdomen. Two tasks: MRI-to-CT (890 cases) and CBCT-to-CT (1,472 cases), evaluated via image similarity (MAE, PSNR, MS-SSIM), segmentation (Dice, HD95), and dosimetric metrics from photon and proton plans. With 803 participants and 12/13 valid submissions, Task 1 top performance reached MAE $64.8\pm21.3$ HU, PSNR $\sim$30 dB, MS-SSIM $\sim$0.936, Dice 0.79, photon $γ_{2\%/2\text{mm}}>98\%$, proton $γ\approx85\%$. Task 2 improved: MAE $48.3\pm13.4$ HU, PSNR 32.6 dB, MS-SSIM 0.968, Dice 0.86, photon $γ>99\%$, proton $γ\approx89\%$. Strong image--segmentation correlations ($ρ=0.78$--$0.79$) but moderate dose correlations confirmed image quality is insufficient as a dosimetric surrogate. Head-and-neck cases were most consistent; thoracic and abdominal cases showed greater variability. Residual errors at tissue interfaces propagate along beam paths, affecting proton dose more than photon. SynthRAD2025 demonstrates that deep learning yields clinically relevant sCTs, especially for CBCT-to-CT, while identifying persistent MRI-to-CT challenges and underscoring dose-based evaluation as essential for clinical validation.

The geometry of the retinal vessel is a key biomarker of vascular diseases, yet clinical evidence remains primarily observational. Existing generative counterfactuals intervene only at the image-level disease label, failing to isolate explicit anatomical structure. To address this limitation, we propose the Bézier Tree Encoding Counterfactual Framework (BTECF). By abstracting vascular networks into interconnected cubic-Bézier segments, BTECF establishes a disease-agnostic representation in which structural topology is explicitly preserved and atomically perturbable. Coupling this encoding with a diffusion-based generator enables parameter-level do-interventions on explicit geometric axes (e.g., tortuosity, caliber) while preserving background fundus textures. We validate BTECF on diabetic retinopathy, together with independent cohorts for ischemic stroke and Alzheimer's disease. Isolated counterfactual interventions produce dose-responsive shifts in classifier predictions; a matched pixel-drop control attenuates this response by an order of magnitude or more, ruling out out-of-distribution generation artifacts. By enforcing causal isolation between vessel topology and pixel-level confounders, BTECF provides a unified generative paradigm for hypothesis verification across systemic diseases. To support reproducibility, the code will be publicly released upon acceptance.

Foundation diffusion models can generate photorealistic natural images, but adapting them to medical imaging remains challenging. In medical adaptation, limited labeled data can exacerbate hallucination-like and clinically implausible synthesis, while existing metrics such as FID or Inception Score do not quantify per-image alignment with pathology-relevant criteria. We introduce the Clinical Alignment Score (CAS), a foundation-model-based proxy for clinical alignment that evaluates generated images along four complementary dimensions beyond visual fidelity. Building on CAS, we propose Clinical Reward-Aligned Finetuning (CRAFT), a reward-based adaptation framework that transfers medical knowledge from multimodal large language models and vision-language models through label-conditioned prompt enrichment, clinical checklists, and differentiable reward optimization. Across four diverse modalities, CRAFT improves CAS and downstream classification performance over strong adaptation baselines. Beyond average CAS gains, CRAFT reduces the empirical low-alignment tail below a real-image reference threshold by 5.5-34.7% points relative to the strongest baseline, corresponding to a 20.4% average relative reduction across datasets. These results indicate fewer hallucination-like generations under CAS, and are corroborated by out-of-family evaluator evaluation, structured checklist auditing, memorization analysis, and a blinded physician preference study on CheXpert.

Class imbalance is a persistent challenge in visual recognition, particularly in safety-critical domains where collecting positive examples is expensive and rare events are inherently underrepresented. We propose a lightweight synthetic data augmentation pipeline that fine-tunes a LoRA adapter on as few as 20-50 real images of a rare class and uses a pretrained diffusion model to generate synthetic samples for training. We systematically vary the synthetic-to-real ratio and evaluate the approach across two structurally different domains: chest X-ray pathology classification (NIH ChestX-ray14) and industrial surface crack detection (Magnetic Tile Defect dataset). All evaluations are performed on held-out sets of real images only. Across both domains, synthetic augmentation consistently improves rare-class recall and F1 compared to training with real data alone. Performance improves with moderate synthetic augmentation and shows diminishing returns as the synthetic ratio increases. These results suggest that LoRA-adapted diffusion models provide a simple and scalable mechanism for augmenting rare classes, enabling effective learning in data-scarce scenarios across heterogeneous visual domains.

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.

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.

In many real-world computer vision applications, including medical imaging and industrial inspection, binary classification tasks are characterized by a severe scarcity of positive samples. A widely adopted solution is to generate synthetic positive data using image-to-image transformations applied to negative samples. However, a fundamental challenge remains: how can we reliably assess whether such synthetic data will improve downstream model performance? In this work, we propose a geometry-driven metric that predicts the utility of synthetic data without requiring model training. Our approach operates in the embedding space of a pre-trained foundation model and represents the dataset through difference vectors between samples. We evaluate whether the weight vector of a linear classifier can be expressed within the subspace spanned by these variations by measuring the relative projection error. Intuitively, if the variations induced by synthetic data capture task-relevant directions, their span can approximate the classifier, resulting in low projection error. Conversely, poor synthetic data fails to span these directions, leading to higher error. Across multiple datasets and architectures, we show that this metric exhibits strong correlation with downstream classification performance of CNNs trained on mixtures of real negative and synthetic positive data. These findings suggest that the proposed metric serves as a practical and informative tool for evaluating synthetic data quality in data-scarce settings.

The scarcity of high-quality imaging data for coronary angiography (CAG) stenosis limits the clinical translation of automated stenosis detection. Synthetic stenosis data provides a practical avenue to augment training sets, improving data quality, diversity, and distributional coverage, and enhancing detection precision and generalization. However, diffusion-based editing commonly relies on soft guidance in a noise-initialized reverse process, offering limited pixel-level precision and structure preservation. We propose the OT-Bridge Editor, which reframes localized editing as a constrained entropic optimal transport (OT) problem and leverages geometric information to steer the generation path, enabling stronger geometric control. Extensive experiments show that our synthesized angiograms consistently improve downstream stenosis detection, yielding substantial relative gains of 27.8% on the public ARCADE benchmark and 23.0% on our multi-center dataset, supported by consistent qualitative results.

Unifying multimodal understanding and generation is a compelling frontier that is beginning to emerge in the medical field. However, the limited existing unified medical models typically treat understanding and generation as disjoint objectives, lacking a meaningful functional synergy. In this work, we identify and address a critical question in unified medical modeling: what form of understanding truly benefits generation. We present SynerMedGen, a unified framework built on the proposed principle of generation-aligned understanding, which synergizes understanding objectives with generation tasks via task alignment. SynerMedGen introduces three generation-aligned understanding tasks and a two-stage training strategy that transfers generation-beneficial representations learned during understanding training to medical image synthesis. Remarkably, even with understanding training alone, our SynerMedGen achieves strong zero-shot performance across 22 medical image synthesis tasks and demonstrates robust generalization to unseen datasets. When combined with generation training, SynerMedGen consistently outperforms state-of-the-art specialized medical image synthesis models as well as recent unified medical models. We also release a large-scale dataset named SynerMed consisting of 1M paired synthesis samples and 2M generation-derived understanding instances to support further research on understanding-generation synergy. Our project can be accessed at https://github.com/piooip/SynerMedGen.

Computed tomography (CT) is indispensable for clinical diagnosis and image-guided interventions but exposes patients to ionizing radiation, motivating the development of safer imaging alternatives. Ultrasound (US) is non-ionizing and widely accessible; however, it is highly operator dependent and lacks quantitative tissue characterization, often leading to diagnostic uncertainty and unnecessary CT examinations. This work presents a 3D ultrasound-derived pseudo-CT (UD-pCT) framework that generates CT-like anatomical reference volumes inferred from US, without aiming to reproduce physically accurate Hounsfield Units. Paired 3D kidney US and CT volumes from the TRUSTED dataset are first spatially aligned using a landmark-based multimodal registration pipeline, creating high-quality paired inputs for supervised training of an adversarial framework. The proposed Bottleneck Transformer Residual U-Net3D (BT-ResUNet3D) model employs a 3D residual encoder-decoder generator augmented with a transformer bottleneck, enabling effective modeling of fine-grained local anatomical structures as well as long-range volumetric dependencies, while a 3D Conditional PatchGAN discriminator enforces local structural realism in the synthesized pseudo-CT volumes. Quantitative evaluation using PSNR and SSIM demonstrates that the proposed method outperforms established baselines in structural fidelity and perceptual image quality. The UD-pCT volumes provide real-time anatomical reference for operator guidance, potentially reducing acquisition variability and unnecessary CT use. A limitation of this study is the relatively small paired dataset, which may limit the generalizability of the proposed model.

We propose a multimodal latent diffusion model that jointly synthesizes volumetric magnetic resonance imaging (MRI) and tabular clinical data within a shared latent space via cross-attention. This approach enables coherent joint representation learning of MRI and tabular modalities for generative modeling. Our model utilizes a variational autoencoder to fuse the two modalities before diffusion-based synthesis, allowing modality-appropriate reconstruction with separate decoders for MRI and tabular data. We evaluated the framework on data from the German National Cohort (NAKO Gesundheitsstudie), comprising over 10,000 participants with MRI scans and clinical tabular features such as age, sex, body measurements, and ethnicity. The generated MRI volumes exhibited anatomical plausibility and body composition consistent with the synthesized tabular attributes. Quantitative evaluation using Fréchet distance and precision-recall metrics confirmed high-fidelity image generation. In the tabular modality, our model outperformed CTGAN across standard evaluation metrics and achieved results comparable to TVAE, demonstrating competitive performance relative to established unimodal baselines. This work is, to our knowledge, the first to demonstrate the feasibility of jointly modeling MRI and mixed-type tabular data in a single latent diffusion framework, offering a proof-of-concept for generating coherent synthetic multimodal patient data and aligning with the broader goal of developing digital twins in healthcare.

Synthesizing longitudinal medical images at controllable disease stages while preserving patient-specific anatomy is hindered by the entanglement of pathological textures and structural features. We address this challenge for ulcerative colitis (UC) endoscopy, where severity follows a continuous ordinal progression along the Mayo Endoscopic Score (MES). Our framework, Disentangled Anatomy-Disease Diffusion (DADD), conditions a latent diffusion model on two complementary embeddings: a pretrained image encoder for patient anatomy and a separately trained ordinal embedder for cumulative disease severity. Since image embeddings inevitably capture disease information, we introduce a Feature Purifier, a cross-attention-based erasure mechanism that identifies and suppresses disease-correlated channels, yielding purified anatomical representations. These cleaned anatomy tokens and target disease tokens are injected into the denoising network via a Triple-Pathway Cross-Attention mechanism with resolution-dependent routing gates. This architecture leverages the U-Net hierarchy, in which different network depths encode global structure versus fine-grained pathological texture. Furthermore, we introduce Delta Steering, a training-free directional signal derived from the ordinal embeddings that enables explicit, single-pass control over disease transitions at inference without requiring additional forward passes. Validated on the LIMUC dataset, our approach produces high-fidelity images across all severity levels and effectively rebalances skewed class distributions, enhancing performance for downstream classification tasks. The dataset is available at zenodo.org/records/5827695 and the code base at github.com/umutdundar99/progressive-stable-diffusion

Accurate synthesis of computed tomography (CT) images from magnetic resonance imaging (MRI) is clinically valuable for cranial applications such as attenuation correction, radiotherapy planning, and image-guided interventions. However, heterogeneity across MRI field strengths and acquisition protocols limits the generalizability of existing methods. In this study, we formulate cranial CT synthesis as a modular, structurally coupled problem and propose a deep learning framework to improve robustness across heterogeneous MRI conditions. The model is designed to adapt to variations in field strength and imaging protocols while preserving anatomical consistency. Experiments on multi-site datasets demonstrate improved performance and generalization compared with conventional approaches. The proposed method enables reliable CT synthesis across heterogeneous MRI settings, supporting broader clinical translation.

The bottleneck in learning-based industrial defect detection is often limited not by model capacity, but by the scarcity of labeled defect data: defects are rare, annotations are expensive, and collecting balanced training sets is slow. We present an end-to-end pipeline for synthetic defect generation and annotation, combining Vision-Language-Model-based prompts, LoRA-adapted diffusion, mask-guided inpainting, and sample filtering with automatic label derivation, and demonstrates the potential of real data with realistic synthetic samples to overcome data scarcity. The evaluation is conducted on, a challenging dataset of pitting defects on ball screw drives, and then on a subset of the Mobile phone screen surface defect segmentation dataset (MSD) dataset to test cross-domain transfer. Beyond downstream detector performance, we analyze key stages of the pipeline, including prompt construction, LoRA selection, and sample filtering with DreamSim and CLIPScore, to understand which synthetic samples are both realistic and useful. Experiments with YOLOv26, YOLOX, and LW-DETR show that synthetic-only training does not replace real data. When combined with real data, synthetic defects can preserve performance and yield modest gains in selected BSData training regimes. The MSD transfer study shows that the overall pipeline structure carries over to a second industrial inspection domain, while also highlighting the importance of domain-specific adaptation and annotation-quality control. Overall, the paper provides an end-to-end assessment of diffusion-based industrial defect synthesis and shows that its strongest value lies in strengthening scarce real datasets rather than substituting for them.

Controllable medical video generation has achieved remarkable progress, but it still lacks interpretability, which requires the alignment of generated contents with physical priors and faithful clinical manifestations. To push the boundaries from mere controllability to interpretability, we propose DepthPilot, the first interpretable framework for colonoscopy video generation. This work takes a step toward trustworthy generation through two synergistic paradigms. To achieve explicit geometric grounding, DepthPilot devises a prior distribution alignment strategy, injecting depth constraints into the diffusion backbone via parameter-efficient fine-tuning to ensure anatomical fidelity. To enhance intrinsic nonlinear modeling under these geometric constraints, DepthPilot employs an adaptive spline denoising module, replacing fixed linear weights with learnable spline functions to capture complex spatio-temporal dynamics. Extensive evaluations across three public datasets and in-house clinical data confirm DepthPilot's robust ability to produce physically consistent videos. It achieves FID scores below 15 across all benchmarks and ranks first in clinician assessments, bridging the gap between "visually realistic" and "clinically interpretable". Moreover, DepthPilot-generated videos are expected to enable reliable 3D reconstruction, facilitating surgical navigation and blind region identification, and serve as a foundation toward the colorectal world model.

Generative vision-language models can produce fluent medical image captions but remain prone to hallucination, over-specific diagnostic claims, and factual inconsistency-serious issues in pathology. We investigate retrieval-guided generation (RGG) as a safer alternative, where captions are formed by summarizing expert text from visually similar cases rather than generated de novo. On the ARCH histopathology dataset, RGG improves semantic alignment with ground truth, achieving cosine similarity of $\approx$0.60 versus $\approx$0.47 from MedGemma, with non-overlapping confidence intervals indicating a robust gain. A pathologist-led qualitative review shows better preservation of morphology-relevant terminology and fewer unsupported diagnoses, while revealing failure modes such as concept mixing and inherited over-specific labeling. Overall, retrieval-guided captioning offers a more transparent and reliable approach with clearer opportunities for auditing than fully generative methods.

Recent medical multimodal foundation models are built as multimodal LLMs (MLLMs) by connecting a CLIP-pretrained vision encoder to an LLM using LLaVA-style finetuning. This two-stage, decoupled approach introduces a projection layer that can distort visual features. This is especially concerning in medical imaging where subtle cues are essential for accurate diagnoses. In contrast, early-fusion generative approaches such as Chameleon eliminate the projection bottleneck by processing image and text tokens within a single unified sequence, enabling joint representation learning that leverages the inductive priors of language models. We present CheXmix, a unified early-fusion generative model trained on a large corpus of chest X-rays paired with radiology reports. We expand on Chameleon's autoregressive framework by introducing a two-stage multimodal generative pretraining strategy that combines the representational strengths of masked autoencoders with MLLMs. The resulting models are highly flexible, supporting both discriminative and generative tasks at both coarse and fine-grained scales. Our approach outperforms well-established generative models across all masking ratios by 6.0% and surpasses CheXagent by 8.6% on AUROC at high image masking ratios on the CheXpert classification task. We further inpaint images over 51.0% better than text-only generative models and outperform CheXagent by 45% on the GREEN metric for radiology report generation. These results demonstrate that CheXmix captures fine-grained information across a broad spectrum of chest X-ray tasks. Our code is at: https://github.com/StanfordMIMI/CheXmix.

Conditional medical image generation plays an important role in many clinically relevant imaging tasks. However, existing methods still face a fundamental challenge in balancing inference efficiency, patient-specific fidelity, and distribution-level plausibility, particularly in high-dimensional 3D medical imaging. In this work, we propose GDM, a generative drifting framework that reformulates deterministic medical image prediction as a multi-objective learning problem to jointly promote distribution-level plausibility and patient-specific fidelity while retaining one-step inference. GDM extends drifting to 3D medical imaging through an attractive-repulsive drift that minimizes the discrepancy between the generator pushforward and the target distribution. To enable stable drifting-based learning in 3D volumetric data, GDM constructs a multi-level feature bank from a medical foundation encoder to support reliable affinity estimation and drifting field computation across complementary global, local, and spatial representations. In addition, a gradient coordination strategy in the shared output space improves optimization balance under competing distribution-level and fidelity-oriented objectives. We evaluate the proposed framework on two representative tasks, MRI-to-CT synthesis and sparse-view CT reconstruction. Experimental results show that GDM consistently outperforms a wide range of baselines, including GAN-based, flow-matching-based, and SDE-based generative models, as well as supervised regression methods, while improving the balance among anatomical fidelity, quantitative reliability, perceptual realism, and inference efficiency. These findings suggest that GDM provides a practical and effective framework for conditional 3D medical image generation.

There is no consensus in the field of synthetic data on concise metrics for quality evaluations or benchmarks on large health datasets, such as historical epidemiological data. This study presents an evaluation of seven recent models from major machine learning families. The models were evaluated using four different datasets, each with a distinct scale. To ensure a fair comparison, we systematically tuned the hyperparameters of each model for each dataset. We propose a methodology for evaluating the fidelity of synthesized joint distributions, aligning metrics with visualization on a single plot. This method is applicable to any dataset and is complemented by a domain-specific analysis of the German Cancer Registries' epidemiological dataset. The analysis reveals the challenges models face in strictly adhering to the medical domain. We hope this approach will serve as a foundational framework for guiding the selection of synthesizers and remain accessible to all stakeholders involved in releasing synthetic datasets.

Objective. Standard Magnetic Resonance Imaging (MRI) reconstruction pipelines discard phase information captured during acquisition, despite evidence that it encodes tissue properties relevant to tumor diagnosis. Current machine learning approaches inherit this limitation by operating exclusively on reconstructed magnitude images. The aim of this study is to build a generative framework which is capable of jointly modeling magnitude and phase information of complex-valued MRI scans. Approach. The proposed generative framework combines a conditional variational autoencoder, which compresses complex-valued MRI scans into compact latent representations while preserving phase coherence, with a flow-matching-based generative model. Synthetic sample quality is assessed via a real-versus-synthetic classifier and by training downstream classifiers on synthetic data for abnormal tissue detection. Main results. The autoencoder preserves phase coherence above 0.997. Real-versus-synthetic classification yields low AUROC values between 0.50 and 0.66 across all acquisition sequences, indicating generated samples are nearly indistinguishable from real data. In downstream normal-versus-abnormal classification, classifiers trained entirely on synthetic data achieve an AUROC of 0.880, surpassing the real-data baseline of 0.842 on a publicly available dataset (fastMRI). This advantage persists on an independent external test set from a different institution with biopsy-confirmed labels. Significance. The proposed framework demonstrates the feasibility of jointly modeling magnitude and phase information for normal and abnormal complex-valued brain MRI data. Beyond synthetic data generation, it establishes a foundation for the usage of complete brain MRI information in future diagnostic applications and enables systematic investigation of how magnitude and phase jointly encode pathology-specific features.

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 to investigate the applicability of state-space modeling for cross-modality medical image translation and assess its performance relative to established convolutional architectures. Specifically, we adapt the SegMamba architecture, originally proposed for segmentation, to perform image-to-image generation. Our 3D Mamba architecture effectively captures complex volumetric features and long-range dependencies, thus allowing accurate CT synthesis while maintaining a relatively low parameter count. 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 Hounsfield 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.

Generative models are increasingly used to augment medical imaging datasets for fairer AI, yet a key assumption often goes unexamined: that generators produce equally high-quality images across demographic groups. Models trained on imbalanced data inherit these imbalances, degrading synthesis for rare subgroups and struggling with intersections absent from training: the imbalanced generator problem. Remedies such as loss reweighting operate at the optimization level and provide limited benefit when training signal is scarce or absent. We propose CompDiff, a hierarchical compositional diffusion framework that addresses this at the representation level. A dedicated Hierarchical Conditioner Network (HCN) decomposes demographic conditioning into single-attribute, pairwise, and composed representations, producing a demographic token concatenated with CLIP embeddings as cross-attention context. This structured factorization encourages parameter sharing across subgroups and supports compositional generalization to rare or unseen intersections. On chest X-rays (MIMIC-CXR) and fundus images (FairGenMed), CompDiff compares favorably against standard fine-tuning and FairDiffusion across image quality (FID 64.3 vs. 75.1), subgroup equity (ES-FID), and zero-shot intersectional generalization (up to 21% FID improvement on held-out intersections). Downstream classifiers trained on CompDiff data show improved AUROC and reduced demographic bias, suggesting that the architectural design of demographic conditioning is an important and underexplored factor in fair medical image generation. Code: https://github.com/mahmoudibrahim98/CompDiff.

Zero-shot MRI reconstruction relies on generative priors, but single-modality unconditional priors produce hallucinations under severe ill-posedness. In many clinical workflows, complementary MRI acquisitions (e.g. high-quality structural scans) are routinely available, yet existing reconstruction methods lack mechanisms to leverage this additional information. We propose MPFlow, a zero-shot multi-modal reconstruction framework built on rectified flow that incorporates auxiliary MRI modalities at inference time without retraining the generative prior to improve anatomical fidelity. Cross-modal guidance is enabled by our proposed self-supervised pretraining strategy, Patch-level Multi-modal MR Image Pretraining (PAMRI), which learns shared representations across modalities. Sampling is jointly guided by data consistency and cross-modal feature alignment using pre-trained PAMRI, systematically suppressing intrinsic and extrinsic hallucinations. Extensive experiments on HCP and BraTS show that MPFlow matches diffusion baselines on image quality using only 20% of sampling steps while reducing tumor hallucinations by more than 15% (segmentation dice score). This demonstrates that cross-modal guidance enables more reliable and efficient zero-shot MRI reconstruction.

Recent advances in generative AI have made synthetic Computed Tomography (CT) images increasingly realistic, enabling promising applications in medical data augmentation while raising serious concerns about clinical safety and data trustworthiness. Detecting AI-generated CT images remains challenging for two key reasons: existing benchmarks cover only limited generation sources, and many detectors are adapted from natural-image forensics without explicitly modeling CT-specific imaging properties. In this paper, we introduce CTForensics, a dataset for detecting AI-generated CT images. CTForensics contains 75,990 2D CT images, including a dedicated test benchmark of 29,990 balanced authentic and generated samples from ten representative CT generative models spanning GAN-based and diffusion-based paradigms. We further propose the Enhanced Spatial-Frequency CT Forgery Detector (ESF-CTFD), a CT-oriented CNN framework built around a Wavelet-Enhanced Central Stem, Multi-Scale Spatial Aggregation, and a Frequency-Aware Prediction Block. The Wavelet-Enhanced Central Stem enhances local intensity correlations and high-frequency residuals, Multi-Scale Spatial Aggregation aligns anatomical features across resolutions with lightweight residual units, and the Frequency-Aware Prediction Block models global spectral artifacts. Extensive experiments on CTForensics show that ESF-CTFD achieves 96.01% mAcc and 99.96% mAP, outperforming existing methods and maintaining strong robustness under realistic perturbations with only a 0.99% average drop. Codes will be available at https://github.com/liyih/CTForensics.

Tau positron emission tomography supports Alzheimer's disease staging but is difficult to scale because of tracer, scanner, and radiation constraints. Synthesis from structural MRI is therefore attractive, but it is a particularly difficult setting. T1-weighted and FLAIR MRI provide anatomy and disease correlated morphology, but they do not directly measure Tau-PET relevant signal. We introduce SFL-Net, a multi-input synthesis framework that predicts Tau-PET from T1-weighted and FLAIR MRI. SFL-Net factorizes the latent representation into shared, T1-specific, FLAIR-specific, and complementary pathways and preserves anatomical detail through latent structural conditioning rather than direct encoder-decoder connections. We evaluated SFL-Net and baseline models using 605 training and 83 validation subjects from ADNI-3 and OASIS-3 datasets. Evaluation included raw image fidelity, standardized uptake value ratio agreement, high uptake overlap, regional Bland-Altman bias, braak derived stage agreement, non-inferiority sensitivity analysis, and latent component Shapley attribution. SFL-Net performed competitively on both clinically relevant and reconstruction metrics, while also delivering explicit source level auditability that conventional UNet derived models lack.

Self-supervised learning (SSL) and diffusion models have respectively advanced representation learning and generative modeling for high-dimensional 3D visual data, yet they are often developed as separate paradigms. Their unification remains challenging under multi-source heterogeneity, as anatomical content must be preserved for analysis while acquisition-related style varies across centers and affects synthesis. In this paper, we propose MeDUET, a 3D Medical image Disentangled UnifiEd PreTraining framework in the variational autoencoder latent space. MeDUET formulates unified pretraining as an empirical factor identifiability problem, aiming to learn domain-invariant content factors for anatomy and domain-specific style factors for appearance. To improve factor separation, MeDUET first uses token demixing with a standard adversarial domain regularizer to establish basic content-style specialization, and further introduces Mixed Factor Token Distillation and Swap-invariance Quadruplet Contrast to reduce mixed-region factor leakage and organize factor spaces with factor-wise invariance and discriminability. With these learned factors, MeDUET transfers effectively to both synthesis and analysis, yielding higher fidelity, faster convergence, and better controllability for synthesis, while achieving competitive or superior domain generalization and label efficiency on diverse datasets, tasks, and modalities. Overall, MeDUET shows that multi-source heterogeneity can serve as useful supervision, with disentanglement providing an effective interface for unifying 3D medical image synthesis and analysis. Our code is available at https://github.com/JK-Liu7/MeDUET.

Cardiac Magnetic Resonance (CMR) imaging provides a comprehensive assessment of cardiac structure and function but remains constrained by high acquisition costs and reliance on expert annotations, limiting the availability of large-scale labeled datasets. In contrast, electrocardiograms (ECGs) are inexpensive, widely accessible, and offer a promising modality for conditioning the generative synthesis of cine CMR. To this end, we propose ECGFlowCMR, a novel ECG-to-CMR generative framework that integrates a Phase-Aware Masked Autoencoder (PA-MAE) and an Anatomy-Motion Disentangled Flow (AMDF) to address two fundamental challenges: (1) the cross-modal temporal mismatch between multi-beat ECG recordings and single-cycle CMR sequences, and (2) the anatomical observability gap due to the limited structural information inherent in ECGs. Extensive experiments on the UK Biobank and a proprietary clinical dataset demonstrate that ECGFlowCMR can generate realistic cine CMR sequences from ECG inputs, enabling scalable pretraining and improving performance on downstream cardiac disease classification and phenotype prediction tasks.

Deep learning models in computational pathology often fail to generalize across cohorts and institutions due to domain shift. Existing approaches either fail to leverage unlabeled data from the target domain or rely on image-to-image translation, which can distort tissue structures and compromise model accuracy. In this work, we propose a semi-supervised domain adaptation (SSDA) framework that utilizes a latent diffusion model trained on unlabeled data from both the source and target domains to generate morphology-preserving and target-aware synthetic images. By conditioning the diffusion model on foundation model features, cohort identity, and tissue preparation method, we preserve tissue structure in the source domain while introducing target-domain appearance characteristics. The target-aware synthetic images, combined with real, labeled images from the source cohort, are subsequently used to train a downstream classifier, which is then tested on the target cohort. The effectiveness of the proposed SSDA framework is demonstrated on the task of lung adenocarcinoma prognostication. The proposed augmentation yielded substantially better performance on the held-out test set from the target cohort, without degrading source-cohort performance. The approach improved the weighted F1 score on the target-cohort held-out test set from 0.611 to 0.706 and the macro F1 score from 0.641 to 0.716. Our results demonstrate that target-aware diffusion-based synthetic data augmentation provides a promising and effective approach for improving domain generalization in computational pathology.

Expert-annotated training data remains the critical bottleneck for AI in histopathology, particularly for rare pathologies where even dozens of cases may be unavailable. While data augmentation offers a solution, existing methods fail to generate sufficiently realistic lesion morphologies that preserve tissue-specific architectures. Here we present PathoGen, a diffusion-based generative model enabling controllable, high-fidelity lesion inpainting into benign histopathology images. We validate PathoGen across four datasets representing kidney, skin, breast, and prostate pathology. Quantitative assessment confirms PathoGen outperforms state-of-the-art baselines in image fidelity and distributional similarity. Evaluation by six expert pathologists revealed that synthetic images by PathoGen were only marginally distinguished from real tissue image slightly above chance (57.75% accuracy), demonstrating strong perceptual realism of PathoGen-generated lesions. PathoGen achieved the highest win rate (35.4%) when pathologists ranked generation quality against all baselines. Crucially, augmenting training sets with PathoGen-synthesized lesions improves segmentation Dice scores by up to 0.18 compared to traditional augmentations, with maximum benefit in data-scarce regimes. By simultaneously generating realistic morphology and pixel-level annotations, PathoGen effectively addresses both data scarcity and annotation cost, two critical bottlenecks in computational pathology development.

Ultra-high resolution 7 tesla (7T) magnetic resonance imaging (MRI) provides detailed anatomical views, offering better signal-to-noise ratio, resolution and tissue contrast than 3T MRI, though at the cost of accessibility. We present an advanced deep learning model for synthesizing 7T brain MRI from 3T brain MRI. Paired 7T and 3T T1-weighted images were acquired from 172 participants (124 cognitively unimpaired, 48 impaired) from the Swedish BioFINDER-2 study. To synthesize 7T MRI from 3T images, we trained two models: a specialized U-Net, and a U-Net integrated with a generative adversarial network (GAN U-Net). Our models outperformed two previous state-of-the-art 3T-to-7T models in image-based evaluation metrics. Four blinded MRI professionals judged our synthetic 7T images as comparable in detail to real 7T images, and superior in subjective visual quality to 7T images, due to the reduction of artifacts. Using both SynthSeg and NextBrain, automated segmentations of the synthetic 7T images were more similar to real 7T segmentations than automated segmentations from the 3T images that were used to synthesize the 7T images. Finally, synthetic 7T images showed similar performance to real 3T images in downstream prediction of cognitive status using MRI derivatives (n=3,168). In all, we show that synthetic T1-weighted brain images approaching 7T quality can be generated from 3T images, which may improve image quality and segmentation, without compromising performance in downstream tasks. Future directions, possible clinical use cases, and limitations are discussed.

Fetal brain tissue segmentation from magnetic resonance imaging (MRI) is crucial for studying neurodevelopment, but remains challenging due to data heterogeneity and limited annotations. Domain randomization (DR) has recently emerged as a promising strategy for single-source domain generalization by synthesizing training images with randomized artifacts, contrast, and resolution. In this work, we investigate how to maximize the out-of-domain (OOD) generalization of DR-based methods. We evaluate several synthetic data generation strategies for DR, with a particular focus on our recently proposed framework, FetalSynthSeg. We show that simple Gaussian mixture-based intensity modeling outperforms more complex physics-based simulations, and that intensity clustering (subdividing tissue classes based on intensity) improves OOD robustness. Evaluated on 348 fetal subjects from four sites spanning 0.55-3T and both T1w and T2w contrasts, FetalSynthSeg reaches state-of-the-art performance on several FeTA 2024 testing datasets (80-85 Dice score) and, for the first time, offers robust segmentation on modalities other than T2w for fetal brain segmentation (80 Dice on dHCP-T1w dataset). Compared with state-of-the-art methods such as BOUNTI, nnU-Net ensemble, and the FeTA 2024 winner, FetalSynthSeg delivers comparable or superior accuracy while maintaining strong robustness across domain shifts. Our code, model weights, and Docker image ready for easy inference are available at https://hub.docker.com/r/vzalevskyi/fetalsynthseg.