Medical Image Synthesis

Low-field (LF) magnetic resonance imaging (MRI) improves accessibility and reduces costs but generally has lower signal-to-noise ratios and degraded contrast compared to high field (HF) MRI, limiting its clinical utility. Simulating LF MRI from HF MRI enables virtual evaluation of novel imaging devices and development of LF algorithms. Existing low field simulators rely on noise injection and smoothing, which fail to capture the contrast degradation seen in LF acquisitions. To this end, we introduce an end-to-end LF-MRI synthesis framework that learns HF to LF image degradation directly from a small number of paired HF-LF MRIs. Specifically, we introduce a novel HF to LF coordinate-image decoupled neural operator (H2LO) to model the underlying degradation process, and tailor it to capture high-frequency noise textures and image structure. Experimental results in T1w and T2w MRI demonstrate that H2LO produces more faithful simulated low-field images than existing parameterized noise synthesis models and popular image-to-image translation models. Furthermore, it improves performance in downstream image enhancement tasks, showcasing its potential to enhance LF MRI diagnostic capabilities.

Synthetic cardiac MRI (CMRI) generation has emerged as a promising strategy to overcome the scarcity of annotated medical imaging data. Recent advances in GANs, VAEs, diffusion probabilistic models, and flow-matching techniques aim to generate anatomically accurate images while addressing challenges such as limited labeled datasets, vendor variability, and risks of privacy leakage through model memorization. Maskconditioned generation improves structural fidelity by guiding synthesis with segmentation maps, while diffusion and flowmatching models offer strong boundary preservation and efficient deterministic transformations. Cross-domain generalization is further supported through vendor-style conditioning and preprocessing steps like intensity normalization. To ensure privacy, studies increasingly incorporate membership inference attacks, nearest-neighbor analyses, and differential privacy mechanisms. Utility evaluations commonly measure downstream segmentation performance, with evidence showing that anatomically constrained synthetic data can enhance accuracy and robustness across multi-vendor settings. This review aims to compare existing CMRI generation approaches through the lenses of fidelity, utility, and privacy, highlighting current limitations and the need for integrated, evaluation-driven frameworks for reliable clinical workflows.

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.

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.

Currently, a central challenge and bottleneck in the deployment and validation of computer-aided diagnosis (CAD) models within the field of medical imaging is data scarcity. For lung cancer, one of the most prevalent types worldwide, limited datasets can delay diagnosis and have an impact on patient outcome. Generative AI offers a promising solution for this issue, but dealing with the complex distribution of full Hounsfield Unit (HU) range lung CT scans is challenging and remains as a highly computationally demanding task. This paper introduces a novel decomposition strategy that synthesizes CT images one HU interval at a time, rather than modelling the entire HU domain at once. This framework focuses on training generative architectures on individual tissue-focused HU windows, then merges their output into a full-range scan via a learned reconstruction network that effectively reverses the HU-windowing process. We further propose multi-head and multi-decoder models to better capture textures while preserving anatomical consistency, with a multi-head VQVAE achieving the best performance for the generative task. Quantitative evaluation shows this approach significantly outperforms conventional 2D full-range baselines, achieving a 6.2% improvement in FID and superior MMD, Precision, and Recall across all HU intervals. The best performance is achieved by a multi-head VQVAE variant, demonstrating that it is possible to enhance visual fidelity and variability while also reducing model complexity and computational cost. This work establishes a new paradigm for structure-aware medical image synthesis, aligning generative modelling with clinical interpretation.

Abdominal CT data are limited by high annotation costs and privacy constraints, which hinder the development of robust segmentation and diagnostic models. We present a Prior-Integrated Variation Modeling (PIVM) framework, a diffusion-based method for anatomically accurate CT image synthesis. Instead of generating full images from noise, PIVM predicts voxel-wise intensity variations relative to organ-specific intensity priors derived from segmentation labels. These priors and labels jointly guide the diffusion process, ensuring spatial alignment and realistic organ boundaries. Unlike latent-space diffusion models, our approach operates directly in image space while preserving the full Hounsfield Unit (HU) range, capturing fine anatomical textures without smoothing. Source code is available at https://github.com/BZNR3/PIVM.

Diffusion probabilistic models have demonstrated significant potential in generating high-quality, realistic medical images, providing a promising solution to the persistent challenge of data scarcity in the medical field. Nevertheless, producing 3D medical volumes with anatomically consistent structures under multimodal conditions remains a complex and unresolved problem. We introduce Sketch2CT, a multimodal diffusion framework for structure-aware 3D medical volume generation, jointly guided by a user-provided 2D sketch and a textual description that captures 3D geometric semantics. The framework initially generates 3D segmentation masks of the target organ from random noise, conditioned on both modalities. To effectively align and fuse these inputs, we propose two key modules that refine sketch features with localized textual cues and integrate global sketch-text representations. Built upon a capsule-attention backbone, these modules leverage the complementary strengths of sketches and text to produce anatomically accurate organ shapes. The synthesized segmentation masks subsequently guide a latent diffusion model for 3D CT volume synthesis, enabling realistic reconstruction of organ appearances that are consistent with user-defined sketches and descriptions. Extensive experiments on public CT datasets demonstrate that Sketch2CT achieves superior performance in generating multimodal medical volumes. Its controllable, low-cost generation pipeline enables principled, efficient augmentation of medical datasets. Code is available at https://github.com/adlsn/Sketch2CT.

Counterfactual image generation enables controlled data augmentation, bias mitigation, and disease modeling. However, existing methods guided by external classifiers or regressors are limited to subject-level factors (e.g., age) and fail to produce localized structural changes, often resulting in global artifacts. Pixel-level guidance using segmentation masks has been explored, but requires user-defined counterfactual masks, which are tedious and impractical. Segmentor-guided Counterfactual Fine-Tuning (Seg-CFT) addressed this by using segmentation-derived measurements to supervise structure-specific variables, yet it remains restricted to global interventions. We propose Positional Seg-CFT, which subdivides each structure into regional segments and derives independent measurements per region, enabling spatially localized and anatomically coherent counterfactuals. Experiments on coronary CT angiography show that Pos-Seg-CFT generates realistic, region-specific modifications, providing finer spatial control for modeling disease progression.

Contrast-enhanced magnetic resonance imaging (CE-MRI) plays a crucial role in brain tumor assessment; however, its acquisition requires gadolinium-based contrast agents (GBCAs), which increase costs and raise safety concerns. Consequently, synthesizing CE-MRI from non-contrast MRI (NC-MRI) has emerged as a promising alternative. Early Generative Adversarial Network (GAN)-based approaches suffered from instability and mode collapse, while diffusion models, despite impressive synthesis quality, remain computationally expensive and often fail to faithfully reproduce critical tumor contrast patterns. To address these limitations, we propose Tumor-Biased Latent Bridge Matching (TuLaBM), which formulates NC-to-CE MRI translation as Brownian bridge transport between source and target distributions in a learned latent space, enabling efficient training and inference. To enhance tumor-region fidelity, we introduce a Tumor-Biased Attention Mechanism (TuBAM) that amplifies tumor-relevant latent features during bridge evolution, along with a boundary-aware loss that constrains tumor interfaces to improve margin sharpness. While bridge matching has been explored for medical image translation in pixel space, our latent formulation substantially reduces computational cost and inference time. Experiments on BraTS2023-GLI (BraSyn) and Cleveland Clinic (in-house) liver MRI dataset show that TuLaBM consistently outperforms state-of-the-art baselines on both whole-image and tumor-region metrics, generalizes effectively to unseen liver MRI data in zero-shot and fine-tuned settings, and achieves inference times under 0.097 seconds per image.

Positron emission tomography (PET) is a widely recognized technique for diagnosing neurodegenerative diseases, offering critical functional insights. However, its high costs and radiation exposure hinder its widespread use. In contrast, magnetic resonance imaging (MRI) does not involve such limitations. While MRI also detects neurodegenerative changes, it is less sensitive for diagnosis compared to PET. To overcome such limitations, one approach is to generate synthetic PET from MRI. Recent advances in generative models have paved the way for cross-modality medical image translation; however, existing methods largely emphasize structural preservation while neglecting the critical need for pathology awareness. To address this gap, we propose PASTA, a novel image translation framework built on conditional diffusion models with enhanced pathology awareness. PASTA surpasses state-of-the-art methods by preserving both structural and pathological details through its highly interactive dual-arm architecture and multi-modal condition integration. Additionally, we introduce a novel cycle exchange consistency and volumetric generation strategy that significantly enhances PASTA's ability to produce high-quality 3D PET images. Our qualitative and quantitative results demonstrate the high quality and pathology awareness of the synthesized PET scans. For Alzheimer's diagnosis, the performance of these synthesized scans improves over MRI by 4%, almost reaching the performance of actual PET. Our code is available at https://github.com/ai-med/PASTA.

Segmentation of enhancement in LGE cardiac MRI is critical for diagnosing various ischemic and non-ischemic cardiomyopathies. However, creating pixel-level annotations for these images is challenging and labor-intensive, leading to limited availability of annotated data. Generative models, particularly diffusion models, offer promise for synthetic data generation, yet many rely on large training datasets and often struggle with fine-grained conditioning control, especially for small or localized features. We introduce LGESynthNet, a latent diffusion-based framework for controllable enhancement synthesis, enabling explicit control over size, location, and transmural extent. Formulated as inpainting using a ControlNet-based architecture, the model integrates: (a) a reward model for conditioning-specific supervision, (b) a captioning module for anatomically descriptive text prompts, and (c) a biomedical text encoder. Trained on just 429 images (79 patients), it produces realistic, anatomically coherent samples. A quality control filter selects outputs with high conditioning-fidelity, which when used for training augmentation, improve downstream segmentation and detection performance, by up-to 6 and 20 points respectively.

Computational pathology has made significant progress in recent years, fueling advances in both fundamental disease understanding and clinically ready tools. This evolution is driven by the availability of large amounts of digitized slides and specialized deep learning methods and models. Multiple self-supervised foundation feature extractors have been developed, enabling downstream predictive applications from cell segmentation to tumor sub-typing and survival analysis. In contrast, generative foundation models designed specifically for histopathology remain scarce. Such models could address tasks that are beyond the capabilities of feature extractors, such as virtual staining. In this paper, we introduce CytoSyn, a state-of-the-art foundation latent diffusion model that enables the guided generation of highly realistic and diverse histopathology H&E-stained images, as shown in an extensive benchmark. We explored methodological improvements, training set scaling, sampling strategies and slide-level overfitting, culminating in the improved CytoSyn-v2, and compared our work to PixCell, a state-of-the-art model, in an in-depth manner. This comparison highlighted the strong sensitivity of both diffusion models and performance metrics to preprocessing-specific details such as JPEG compression. Our model has been trained on a dataset obtained from more than 10,000 TCGA diagnostic whole-slide images of 32 different cancer types. Despite being trained only on oncology slides, it maintains state-of-the-art performance generating inflammatory bowel disease images. To support the research community, we publicly release CytoSyn's weights, its training and validation datasets, and a sample of synthetic images in this repository: https://huggingface.co/Owkin-Bioptimus/CytoSyn.

Multi-site neuroimaging analysis is fundamentally confounded by scanner-induced covariate shifts, where the marginal distribution of voxel intensities $P(\mathbf{x})$ varies non-linearly across acquisition protocols while the conditional anatomy $P(\mathbf{y}|\mathbf{x})$ remains constant. This is particularly detrimental to radiomic reproducibility, where acquisition variance often exceeds biological pathology variance. Existing statistical harmonization methods (e.g., ComBat) operate in feature space, precluding spatial downstream tasks, while standard deep learning approaches are theoretically bounded by local effective receptive fields (ERF), failing to model the global intensity correlations characteristic of field-strength bias. We propose SA-CycleGAN-2.5D, a domain adaptation framework motivated by the $HΔH$-divergence bound of Ben-David et al., integrating three architectural innovations: (1) A 2.5D tri-planar manifold injection preserving through-plane gradients $\nabla_z$ at $O(HW)$ complexity; (2) A U-ResNet generator with dense voxel-to-voxel self-attention, surpassing the $O(\sqrt{L})$ receptive field limit of CNNs to model global scanner field biases; and (3) A spectrally-normalized discriminator constraining the Lipschitz constant ($K_D \le 1$) for stable adversarial optimization. Evaluated on 654 glioma patients across two institutional domains (BraTS and UPenn-GBM), our method reduces Maximum Mean Discrepancy (MMD) by 99.1% ($1.729 \to 0.015$) and degrades domain classifier accuracy to near-chance (59.7%). Ablation confirms that global attention is statistically essential (Cohen's $d = 1.32$, $p < 0.001$) for the harder heterogeneous-to-homogeneous translation direction. By bridging 2D efficiency and 3D consistency, our framework yields voxel-level harmonized images that preserve tumor pathophysiology, enabling reproducible multi-center radiomic analysis.

Medical image generators trained on imbalanced data can fail at demographic intersections absent from training. We introduce CompDiff, which encodes age, sex and race separately and composes supervised demographic tokens alongside clinical text. Across chest radiographs and fundus images, CompDiff improves overall and subgroup fidelity relative to prompt conditioning (RoentGen-v2) and loss reweighting (FairDiffusion). It generalises in zero-shot generation to 16 chest X-ray intersections excluded from training, achieving the lowest mean FID-RadImageNet in every intersection. In a blinded reader study of these unseen intersections, two radiologists gave CompDiff the highest mean scores among generators for anatomical realism and agreement with the clinical impression, and selected its images most often as the most realistic. Pretraining with CompDiff images improved downstream classification, while CompDiff audit cohorts reduced estimation error on rare intersections. These findings support compositional demographic conditioning for extending medical image synthesis to underserved populations. Code: https://github.com/mahmoudibrahim98/CompDiff

Despite recent advances in deep generative modeling, skin lesion classification systems remain constrained by the limited availability of large, diverse, and well-annotated clinical datasets, resulting in class imbalance between benign and malignant lesions and consequently reduced generalization performance. We introduce DermaFlux, a rectified flow-based text-to-image generative framework that synthesizes clinically grounded skin lesion images from natural language descriptions of dermatological attributes. Built upon Flux.1, DermaFlux is fine-tuned using parameter-efficient Low-Rank Adaptation (LoRA) on a large curated collection of publicly available clinical image datasets. We construct image-text pairs using synthetic textual captions generated by Llama 3.2, following established dermatological criteria including lesion asymmetry, border irregularity, and color variation. Extensive experiments demonstrate that DermaFlux generates diverse and clinically meaningful dermatology images that improve binary classification performance by up to 6% when augmenting small real-world datasets, and by up to 9% when classifiers are trained on DermaFlux-generated synthetic images rather than diffusion-based synthetic images. Our ImageNet-pretrained ViT fine-tuned with only 2,500 real images and 4,375 DermaFlux-generated samples achieves 78.04% binary classification accuracy and an AUC of 0.859, surpassing the next best dermatology model by 8%.

Multiplex immunofluorescence (mIF) enables simultaneous single-cell quantification of multiple biomarkers within intact tissue architecture, yet its high reagent cost, multi-round staining protocols, and need for specialized imaging platforms limit routine clinical adoption. Virtual staining can synthesize mIF channels from widely available brightfield immunohistochemistry (IHC), but current translators optimize pixel-level fidelity without explicitly constraining nuclear morphology. In pathology, this gap is clinically consequential: subtle distortions in nuclei count, shape, or spatial arrangement propagate directly to quantification endpoints such as the Ki67 proliferation index, where errors of a few percent can shift treatment-relevant risk categories. This work introduces a supervision-free, architecture-agnostic conditioning strategy that injects a continuous cell probability map from a pretrained nuclei segmentation foundation model as an explicit input prior, together with a variance-preserving regularization term that matches local intensity statistics to maintain cell-level heterogeneity in synthesized fluorescence channels. The soft prior retains gradient-level boundary information lost by binary thresholding, providing a richer conditioning signal without task-specific tuning. Controlled experiments across Pix2Pix with U-Net and ResNet generators, deterministic regression U-Net, and conditional diffusion on two independent datasets demonstrate consistent improvements in nuclei count fidelity and perceptual quality, as the sole modifications. Code will be made publicly available upon acceptance.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with survival outcomes critically dependent on early and accurate detection. When low-dose computed tomography (LDCT) findings are indeterminate, clinicians typically defer diagnosis pending follow-up CT imaging obtained up to 12 months later, inevitably delaying treatment for patients with malignant nodules. To address this clinical gap, we propose Nodule-Aligned Multimodal (Latent) Diffusion (NAMD), a novel generative framework that synthesizes one-year follow-up nodule CT images conditioned on the baseline CT scan, quantitative nodule biomarkers, and patient-level Electronic Health Records (EHR), enabling timely prediction of nodule malignant progression without requiring actual follow-up scans. NAMD introduces two key contributions: (i) a nodule-aligned latent space regularized so that embedding distances reflect clinically meaningful biomarker changes, and (ii) an LLM-driven multimodal conditioning mechanism encoding heterogeneous EHR data into the diffusion backbone. Evaluated on the National Lung Screening Trial (NLST), our method's synthetic follow-up images achieve an AUROC of 0.805 and an AUPRC of 0.346 for lung nodule malignancy prediction, outperforming both the baseline LDCT performance without virtual follow-up generation, and existing state-of-the-art conditional generation methods, while maintaining competitive image quality. These findings suggest that NAMD enables earlier and more accurate lung cancer diagnosis by capturing clinically meaningful features of nodule progression.

Deep learning models for chest X-ray diagnosis are constrained by limited coverage of clinically meaningful concept combinations in publicly available training datasets. While synthetic image generation has been explored to increase data diversity, existing methods rarely enforce clinical or anatomical constraints, limiting utility for improving model reliability. We propose CARPA, a clinically aware and anatomically grounded framework for synthetic chest X-ray generation that applies targeted perturbations to clinical concept vectors while preserving anatomical structure. By producing anatomically faithful synthetic images with controlled concept insertions and deletions, CARPA expands clinically relevant concept coverage. We evaluate CARPA across seven backbone architectures by fine-tuning models on synthetic subsets and testing on a held-out MIMIC-CXR benchmark. Compared to prior concept perturbation approaches, fine-tuning on CARPA-generated images consistently improves precision-recall performance, reduces predictive uncertainty, and improves model calibration. Structural and semantic analyses demonstrate high anatomical fidelity, strong concept alignment, and low semantic uncertainty. Evaluation by two expert radiologists further confirms realism and clinical agreement. Together, these results show that anatomically grounded concept perturbations enable more effective use of synthetic data, improving both performance and reliability of chest X-ray classification models and supporting safer clinical deployment.

Echocardiography is widely used for assessing cardiac function, where clinically meaningful parameters such as left-ventricular ejection fraction (EF) play a central role in diagnosis and management. Generative models capable of synthesising realistic echocardiogram videos with explicit control over such parameters are valuable for data augmentation, counterfactual analysis, and specialist training. However, existing approaches typically rely on computationally expensive multi-step sampling and aggressive temporal normalisation, limiting efficiency and applicability to heterogeneous real-world data. We introduce EchoLVFM, a one-step latent video flow-matching framework for controllable echocardiogram generation. Operating in the latent space, EchoLVFM synthesises temporally coherent videos in a single inference step, achieving a $\mathbf{\sim 50\times}$ improvement in sampling efficiency compared to multi-step flow baselines while maintaining visual fidelity. The model supports global conditioning on clinical variables, demonstrated through precise control of EF, and enables reconstruction and counterfactual generation from partially observed sequences. A masked conditioning strategy further removes fixed-length constraints, allowing shorter sequences to be retained rather than discarded. We evaluate EchoLVFM on the CAMUS dataset under challenging single-frame conditioning. Quantitative and qualitative results demonstrate competitive video quality, strong EF adherence, and 57.9% discrimination accuracy by expert clinicians which is close to chance. These findings indicate that efficient, one-step flow matching can enable practical, controllable echocardiogram video synthesis without sacrificing fidelity. Code available at: https://github.com/EngEmmanuel/EchoLVFM

The translation from Magnetic resonance imaging (MRI) to Computed tomography (CT) has been proposed as an effective solution to facilitate MRI-only clinical workflows while limiting exposure to ionizing radiation. Although numerous Generative Adversarial Network (GAN) architectures have been proposed for MRI-to-CT translation, systematic and fair comparisons across heterogeneous models remain limited. We present a comprehensive benchmark of ten GAN architectures evaluated on the SynthRAD2025 dataset across three anatomical districts (abdomen, thorax, head-and-neck). All models were trained under a unified validation protocol with identical preprocessing and optimization settings. Performance was assessed using complementary metrics capturing voxel-wise accuracy, structural fidelity, perceptual quality, and distribution-level realism, alongside an analysis of computational complexity. Supervised Paired models consistently outperformed Unpaired approaches, confirming the importance of voxel-wise supervision. Pix2Pix achieved the most balanced performance across districts while maintaining a favorable quality-to-complexity trade-off. Multi-district training improved structural robustness, whereas intra-district training maximized voxel-wise fidelity. This benchmark provides quantitative and computational guidance for model selection in MRI-only radiotherapy workflows and establishes a reproducible framework for future comparative studies. To ensure the reproducibility of our experiments we make our code public, together with the overall results, at the following link:https://github.com/arco-group/MRI_TO_CT.git

Melanoma is the most lethal form of skin cancer, and early detection is critical for improving patient outcomes. Although dermoscopy combined with deep learning has advanced automated skin-lesion analysis, progress is hindered by limited access to large, well-annotated datasets and by severe class imbalance, where melanoma images are substantially underrepresented. To address these challenges, we present the first systematic benchmarking study comparing four GAN architectures-DCGAN, StyleGAN2, and two StyleGAN3 variants (T/R)-for high-resolution melanoma-specific synthesis. We train and optimize all models on two expert-annotated benchmarks (ISIC 2018 and ISIC 2020) under unified preprocessing and hyperparameter exploration, with particular attention to R1 regularization tuning. Image quality is assessed through a multi-faceted protocol combining distribution-level metrics (FID), sample-level representativeness (FMD), qualitative dermoscopic inspection, downstream classification with a frozen EfficientNet-based melanoma detector, and independent evaluation by two board-certified dermatologists. StyleGAN2 achieves the best balance of quantitative performance and perceptual quality, attaining FID scores of 24.8 (ISIC 2018) and 7.96 (ISIC 2020) at gamma=0.8. The frozen classifier recognizes 83% of StyleGAN2-generated images as melanoma, while dermatologists distinguish synthetic from real images at only 66.5% accuracy (chance = 50%), with low inter-rater agreement (kappa = 0.17). In a controlled augmentation experiment, adding synthetic melanoma images to address class imbalance improved melanoma detection AUC from 0.925 to 0.945 on a held-out real-image test set. These findings demonstrate that StyleGAN2-generated melanoma images preserve diagnostically relevant features and can provide a measurable benefit for mitigating class imbalance in melanoma-focused machine learning pipelines.

This paper presents NOIR, a framework that reframes core medical imaging tasks as operator learning between continuous function spaces, challenging the prevailing paradigm of discrete grid-based deep learning. Instead of operating on fixed pixel or voxel grids, NOIR embeds discrete medical signals into shared Implicit Neural Representations and learns a Neural Operator that maps between their latent modulations, enabling resolution-independent function-to-function transformations. We evaluate NOIR across multiple 2D and 3D downstream tasks, including segmentation, shape completion, image-to-image translation, and image synthesis, on several public datasets such as Shenzhen, OASIS-4, SkullBreak, fastMRI, as well as an in-house clinical dataset. It achieves competitive performance at native resolution while demonstrating strong robustness to unseen discretizations, and empirically satisfies key theoretical properties of neural operators. The project page is available here: https://github.com/Sidaty1/NOIR-io.

Although diffusion models have achieved remarkable progress in multi-modal magnetic resonance imaging (MRI) translation tasks, existing methods still tend to suffer from anatomical inconsistencies or degraded texture details when handling arbitrary missing-modality scenarios. To address these issues, we propose a latent diffusion-based multi-modal MRI translation framework, termed MSG-LDM. By leveraging the available modalities, the proposed method infers complete structural information, which preserves reliable boundary details. Specifically, we introduce a style--structure disentanglement mechanism in the latent space, which explicitly separates modality-specific style features from shared structural representations, and jointly models low-frequency anatomical layouts and high-frequency boundary details in a multi-scale feature space. During the structure disentanglement stage, high-frequency structural information is explicitly incorporated to enhance feature representations, guiding the model to focus on fine-grained structural cues while learning modality-invariant low-frequency anatomical representations. Furthermore, to reduce interference from modality-specific styles and improve the stability of structure representations, we design a style consistency loss and a structure-aware loss. Extensive experiments on the BraTS2020 and WMH datasets demonstrate that the proposed method outperforms existing MRI synthesis approaches, particularly in reconstructing complete structures. The source code is publicly available at https://github.com/ziyi-start/MSG-LDM.

Low-field to high-field MRI synthesis has emerged as a promising strategy to improve image quality when access to high-field scanners is limited. However, in ultra-low-field settings, the degradation of anatomical detail is spatially heterogeneous: structurally ambiguous regions are more susceptible to unstable high-frequency generation, which may produce anatomically inconsistent textures and boundaries. This issue is particularly problematic when synthesized images are used for downstream quantitative analysis. We therefore study how to make diffusion-based LF-to-HF synthesis more spatially reliable, rather than only sharper on average. To this end, we propose a reliability-guided diffusion framework (ReDiff) with two complementary inference-time mechanisms. First, a reliability-guided sampling strategy attenuates unstable reverse-diffusion updates in regions with weak low-field support. Second, an uncertainty-aware candidate selection scheme aggregates multiple stochastic reconstructions according to spatial consensus and predictive uncertainty. Beyond aggregate image quality, we test whether the uncertainty is itself a usable reliability signal. Experiments on paired 64mT$\rightarrow$3T MRI datasets show that ReDiff attains the lowest LPIPS across three contrasts and two datasets while remaining competitive on PSNR and SSIM, and downstream segmentation analysis indicates better preservation of anatomical structure.

Medical image synthesis is crucial for alleviating data scarcity and privacy constraints. However, fine-tuning general text-to-image (T2I) models remains challenging, mainly due to the significant modality gap between complex visual details and abstract clinical text. In addition, semantic entanglement persists, where coarse-grained text embeddings blur the boundary between anatomical structures and imaging styles, thus weakening controllability during generation. To address this, we propose a Visually-Guided Text Disentanglement framework. We introduce a cross-modal latent alignment mechanism that leverages visual priors to explicitly disentangle unstructured text into independent semantic representations. Subsequently, a Hybrid Feature Fusion Module (HFFM) injects these features into a Diffusion Transformer (DiT) through separated channels, enabling fine-grained structural control. Experimental results in three datasets demonstrate that our method outperforms existing approaches in terms of generation quality and significantly improves performance on downstream classification tasks. The source code is available at https://github.com/hx111/VG-MedGen.

Controllable pathology image synthesis requires reliable regulation of spatial layout, tissue morphology, and semantic detail. However, existing text-guided diffusion models offer only coarse global control and lack the ability to enforce fine-grained structural constraints. Progress is further limited by the absence of large datasets that pair patch-level spatial layouts with detailed diagnostic descriptions, since generating such annotations for gigapixel whole-slide images is prohibitively time-consuming for human experts. To overcome these challenges, we first develop a scalable multi-agent LVLM annotation framework that integrates image description, diagnostic step extraction, and automatic quality judgment into a coordinated pipeline, and we evaluate the reliability of the system through a human verification process. This framework enables efficient construction of fine-grained and clinically aligned supervision at scale. Building on the curated data, we propose In-Context Diffusion Transformer (IC-DiT), a layout-aware generative model that incorporates spatial layouts, textual descriptions, and visual embeddings into a unified diffusion transformer. Through hierarchical multimodal attention, IC-DiT maintains global semantic coherence while accurately preserving structural and morphological details. Extensive experiments on five histopathology datasets show that IC-DiT achieves higher fidelity, stronger spatial controllability, and better diagnostic consistency than existing methods. In addition, the generated images serve as effective data augmentation resources for downstream tasks such as cancer classification and survival analysis.

Multimodal neuroimaging provides complementary insights for Alzheimer's disease diagnosis, yet clinical datasets frequently suffer from missing modalities. We propose ACADiff, a framework that synthesizes missing brain imaging modalities through adaptive clinical-aware diffusion. ACADiff learns mappings between incomplete multimodal observations and target modalities by progressively denoising latent representations while attending to available imaging data and clinical metadata. The framework employs adaptive fusion that dynamically reconfigures based on input availability, coupled with semantic clinical guidance via GPT-4o-encoded prompts. Three specialized generators enable bidirectional synthesis among sMRI, FDG-PET, and AV45-PET. Evaluated on ADNI subjects, ACADiff achieves superior generation quality and maintains robust diagnostic performance even under extreme 80% missing scenarios, outperforming all existing baselines. To promote reproducibility, code is available at https://github.com/rongzhou7/ACADiff

Brain tumors result in 20 years of lost life on average. Standard therapies induce complex structural changes in the brain that are monitored through MRI. Recent developments in artificial intelligence (AI) enable conditional multimodal image generation from clinical data. In this study, we investigate AI-driven generation of follow-up MRI in patients with intracranial tumors through conditional image generation. This approach enables realistic modeling of post-radiotherapy changes, allowing for treatment optimization. The public SAILOR dataset of 25 patients was used to create a 2D rectified flow model conditioned on axial slices of pre-treatment MRI and RT dose maps. Cross-attention conditioning was used to incorporate temporal and chemotherapy data. The resulting images were validated with structural similarity index measure (SSIM), peak signal-to-noise ratio (PSNR), Dice scores and Jacobian determinants. The resulting model generates realistic follow-up MRI for any time point, while integrating treatment information. Comparing real versus predicted images, SSIM is 0.88, and PSNR is 22.82. Tissue segmentations from real versus predicted MRI result in a mean Dice-Sørensen coefficient (DSC) of 0.91. The rectified flow (RF) model enables up to 250x faster inference than Denoising Diffusion Probabilistic Models (DDPM). The proposed model generates realistic follow-up MRI in real-time, preserving both semantic and visual fidelity as confirmed by image quality metrics and tissue segmentations. Conditional generation allows counterfactual simulations by varying treatment parameters, producing predicted morphological changes. This capability has potential to support adaptive treatment dose planning and personalized outcome prediction for patients with intracranial tumors. Code will be available upon peer-reviewed publication at: https://github.com/SelenaIHuisman/RF-GlioPREDICT

Text-conditioned generative models for volumetric medical imaging provide semantic control but lack explicit anatomical guidance, often resulting in outputs that are spatially ambiguous or anatomically inconsistent. In contrast, structure-driven methods ensure strong anatomical consistency but typically assume access to ground-truth annotations, which are unavailable when the target image is to be synthesized. We propose a retrieval-augmented approach for Text-to-CT generation that integrates semantic and anatomical information under a realistic inference setting. Given a radiology report, our method retrieves a semantically related clinical case using a 3D vision-language encoder and leverages its associated anatomical annotation as a structural proxy. This proxy is injected into a text-conditioned latent diffusion model via a ControlNet branch, providing coarse anatomical guidance while maintaining semantic flexibility. Experiments on the CT-RATE dataset show that retrieval-augmented generation improves image fidelity and clinical consistency compared to text-only baselines, while additionally enabling explicit spatial controllability, a capability inherently absent in such approaches. Further analysis highlights the importance of retrieval quality, with semantically aligned proxies yielding consistent gains across all evaluation axes. This work introduces a principled and scalable mechanism to bridge semantic conditioning and anatomical plausibility in volumetric medical image synthesis. Code is available at https://github.com/arco-group/RAGText2CT.

Precise prognostic modeling of glioblastoma (GBM) under varying treatment interventions is essential for optimizing clinical outcomes. While generative AI has shown promise in simulating GBM evolution, existing methods typically treat interventions as static conditional inputs rather than dynamic decision variables. Consequently, they fail to capture the complex, reciprocal interplay between tumor evolution and treatment response. To bridge this gap, we present Brain-WM, a pioneering brain GBM world model that unifies next-step treatment prediction and future MRI generation, thereby capturing the co-evolutionary dynamics between tumor and treatment. Specifically, Brain-WM encodes spatiotemporal dynamics into a shared latent space for joint autoregressive treatment prediction and flow-based future MRI generation. Then, instead of a conventional monolithic framework, Brain-WM adopts a novel Y-shaped Mixture-of-Transformers (MoT) architecture. This design structurally disentangles heterogeneous objectives, successfully leveraging cross-task synergies while preventing feature collapse. Finally, a synergistic multi-timepoint mask alignment objective explicitly anchors latent representations to anatomically grounded tumor structures and progression-aware semantics. Extensive validation on internal and external multi-institutional cohorts demonstrates the superiority of Brain-WM, achieving 91.5% accuracy in treatment planning and SSIMs of 0.8524, 0.8581, and 0.8404 for FLAIR, T1CE, and T2W sequences, respectively. Ultimately, Brain-WM offers a robust clinical sandbox for optimizing patient healthcare. The source code is made available at https://github.com/thibault-wch/Brain-GBM-world-model.