Medical Image Synthesis

AI-driven image-to-image synthesis is rapidly advancing, with growing applications in medical imaging. Multi-modal image analysis plays a crucial role in optimizing examination quality, yet acquiring multiple imaging modalities in clinical settings remains resource-intensive and time-consuming, especially for 3D imaging. To address this challenge, we propose a novel image-to-image translation model based on Brownian Bridge Diffusion Models (BBDM), which synthesizes magnetic resonance imaging (MRI) sequences from 2D axial slices. Our approach integrates a variational encoder-guided diffusion mechanism, leveraging probabilistic image distributions to enhance synthesis quality. Evaluated on the BraTS 2021 dataset, our Probabilistic-BBDM (Prob-BBDM) achieves superior performance across multiple translation tasks, reaching up to 88.46% SSIM and 26.09 dB PSNR, with consistent improvements over baselines. Notably, our diffusion process requires only 4 steps, making it computationally efficient while maintaining high-quality synthesis. To further validate generalizability, we test Prob-BBDM on an external third-party dataset, demonstrating consistent performance across domains. Additionally, we assess the clinical utility of the synthesized slices by using them as input to a pre-trained segmentation model. Tumor segmentation yields a Dice score of 88.71% and an HD95 of 3.49 mm, confirming that the synthesized slices preserve critical diagnostic information. These results highlight the potential of Prob-BBDM for high-quality, efficient, and generalizable MRI synthesis, offering a promising step toward improved medical image translation.

Universal segmentation models exhibit significant potential for diverse tasks involving different imaging modalities and segmentation objectives. Task-Incremental Learning provides a privacy-preserving approach to continually evolve a universal model on tasks from sequentially-arriving medical departments. However, training the model solely on the incoming task induces forgetting on past tasks, since consecutive tasks exhibit concurrent shifts in image appearance and segmentation objective. To address this problem, we propose a novel Coupled Comprehensive Generative Replay (C^2GR) framework that simultaneously synthesizes image-mask pairs of previous tasks to mitigate forgetting under concurrent appearance and objective shifts. This requires preserving image-mask correspondence for structure-realistic generation and bridging asynchronous optimization of the generator and segmentor for segmentation-oriented generation. Specifically, we propose a Bayesian Joint Diffusion (BJD) method that formulates the correspondence as conditional distributions optimized via conditional denoising. Furthermore, we develop a Relation-aware Unified Prompt Synchronization (RUPS) scheme to simultaneously modulate the generator and segmentor via a shared task-relation-aware prompt for synchronizing their optimization. Experiments on 20 tasks spanning diverse modalities and objectives demonstrate that C^2GR exhibits only a 2.44% drop in overall performance compared to joint training with all task data, effectively alleviating forgetting from the concurrent shifts. Our code will be made publicly available at https://github.com/mar-cry/C2GR.

While longitudinal brain PET imaging is the gold standard for quantifying the spatiotemporal accumulation of Beta-amyloid, its widespread clinical utility is constrained by high operational costs and cumulative radiation risks. Recent deep generative models show promise in longitudinal image synthesis; however, they often fail to capture subtle pathological progression due to identity drift and a persistent bias toward trivially replicating baseline signal intensities rather than modeling temporal transition. To this end, we propose Delta-Diffusion, a novel progression-aware framework that redefines longitudinal PET synthesis as a conditional Poisson Diffusion Bridge (PDB) process. Unlike standard diffusion models that start from Gaussian noise, our PDB formulation is mathematically anchored to the subject's baseline PET, effectively transforming the generative task into a conditional distribution transition of the amyloid trajectory. To handle heteroscedastic nature of PET imaging, we introduce a physically-grounded Poisson perturbation within a Diffusion Transformer (DiT). This architecture uses adaptive scale-shift modulation to precisely calibrate the synthesis with the elapsed clinical interval and structural MRI context. A volume-of-interest balanced objective is designed to emphasize sparse, high-risk regions of amyloid accumulation. Validated on two cohorts with 542 subjects, Delta-Diffusion demonstrates superior performance in capturing longitudinal variations in amyloid deposition compared to state-of-the-art methods, offering a robust computational framework for tracking disease progression.

The ability to synthesize realistic X-ray images has catalyzed the development of AI models for X-ray image-guided procedures, which otherwise suffer from a lack of available annotated data. Prior work has demonstrated the effectiveness of mechanistic simulation of digitally reconstructed radiographs (DRRs) as a training data source for a myriad of tasks, including segmentation and anatomical landmark detection, with comparable or superior performance to real data training. However, mechanistic DRR synthesis still relies on the availability of annotated high-resolution anatomical models. Deriving these from CT images of real patients or specimens imposes an undesirable bottleneck on data quantity and variability. In this work, we explore two methods for synthesizing training data: (1) a 3D conditional latent diffusion model that generates CT volumes to use as inputs for mechanistic DRR generation without real, 3D anatomical models, and (2) a view-conditioned 2D diffusion model that produces synthetic X-rays. In controlled experiments, we demonstrate that synthetic 2D diffusion-based X-rays can be used to train an anatomical landmark detection model that generalized to real X-ray images with performance rivaling that of a model trained on real X-ray images. Thus, we provide preliminary evidence that synthetic, 2D diffusion-based training data can substitute for real X-ray data, identifying a promising avenue towards generating large, diverse datasets for training robust AI models in interventional X-ray imaging.

Generating high-resolution 3D CT volumes with fine details remains challenging due to substantial computational demands and optimization difficulties inherent to existing generative models. In this paper, we propose the Pixel-Level Residual Diffusion Transformer (PRDiT), a scalable generative framework that synthesizes high-quality 3D medical volumes directly at voxel-level. PRDiT introduces a two-stage training architecture comprising 1) a local denoiser in the form of an MLP-based blind estimator operating on overlapping 3D patches to separate low-frequency structures efficiently, and 2) a global residual diffusion transformer employing memory-efficient attention to model and refine high-frequency residuals across entire volumes. This coarse-to-fine modeling strategy simplifies optimization, enhances training stability, and effectively preserves subtle structures without the limitations of an autoencoder bottleneck. Extensive experiments conducted on the LIDC-IDRI and RAD-ChestCT datasets demonstrate that PRDiT consistently outperforms state-of-the-art models, such as HA-GAN, 3D LDM and WDM-3D, achieving significantly lower 3D FID, MMD and Wasserstein distance scores.

Three-dimensional (3D) brain MRI is central to clinical neurology and neuro-oncology, where generative models could augment under-represented cohorts, simulate disease trajectories, and support privacy-preserving data sharing. Latent diffusion has been the go-to solution for modeling imaging data, but it places two competing demands on the tokenizer: encoder embeddings must retain the clinical information that downstream tasks act on, and the decoder must reconstruct anatomically faithful volumes. Existing reconstruction-driven tokenizers achieve the second at the expense of the first. To address this, we introduce a fully volumetric masked-autoencoder (MAE) based tokenizer for 3D brain MRI latent diffusion, decoupling encoder and decoder: a frozen 3D MAE encoder produces clinically informative embeddings, while a dedicated CNN decoder reconstructs voxels from a linear projection of those embeddings. We pretrain the encoder on 35,309 volumes from 18 public cohorts spanning four modalities, ten disease categories, and 200+ acquisition sites, and demonstrate its dual utility in two settings. First, on a 23-task linear-probing benchmark, the encoder outperforms or matches SOTA models (i.e., BrainIAC, BrainSegFounder, and MedicalNet) on 21 of 23 tasks. Second, a conditional diffusion transformer (DiT) trained on these clinically informative embeddings supports both conditional generation across six variables and patient-specific longitudinal forecasting. Together these results establish a single 3D brain-MRI embedding space capable of both downstream clinical tasks and controllable generation.

We introduce the first generative foundation model for chest radiograph synthesis trained from scratch at the billion-parameter scale. Existing radiographic AI models often suffer from poor generalisation across patient subpopulations, institutions, and acquisition settings, resulting in limited real-world clinical utility. Controlled, high-fidelity synthesis of chest radiographs is a promising path toward diversifying clinical datasets and evaluating the robustness of diagnostic models. Therefore, we present the largest specialist generative foundation model for chest radiographs to date, with over 1.3B parameters, trained for 1.6T tokens on a curated, heterogeneous dataset comprising 1.2M radiographs and clinical expert-guided metadata. Our model supports controllable radiograph generation and editing across multiple demographic subgroups, acquisition views, and a dozen pathologies. Moreover, we significantly advance the state of the art in radiograph synthesis fidelity, producing images that are indistinguishable from real radiographs to clinical experts.

Recent advances in generative machine learning models have significantly improved medical imaging, offering promising solutions for data augmentation, privacy preservation, and improved model generalization. However, synthesizing high-quality structural MRI data for Alzheimer's Disease (AD) remains challenging due to the subtle, region-specific, and progressive anatomical changes associated with neurodegeneration. In this paper, we extend the Med-DDPM conditional diffusion model -- originally designed for brain tumor synthesis -- to generate 3D structural MRIs specifically tailored to AD. We adopted Med-DDPM due to its established stability and structural fidelity compared to other generative models, which makes it particularly suitable for capturing the subtle anatomical changes characteristic of AD. Our approach conditions the diffusion process on anatomical segmentation masks derived from the ADNI dataset, incorporating key AD-relevant brain structures into the generation process. We systematically evaluate the quality and utility of the synthetic images by training segmentation models on real, synthetic, and hybrid (mixed) datasets. Experimental results demonstrate that segmentation models trained exclusively on synthetic data achieve comparable Dice scores (0.6532) to those trained on real data (0.6513), while exhibiting significantly enhanced recall. Notably, models trained on hybrid datasets (mixing real and synthetic images) outperform both real and synthetic-only baselines, achieving a Dice score of 0.7244. These findings underscore the successful use of conditional diffusion models for generating anatomically accurate, AD-specific synthetic MRIs, and highlight their potential for enhancing training data availability, improving diagnostic accuracy, and promoting research reproducibility in neuroimaging studies.

Multi-contrast magnetic resonance imaging (MRI) provides complementary information for clinical diagnosis. However, acquiring all MRI sequences is often time-consuming and costly. Recent generative models perform cross-contrast synthesis to address this issue by inferring absent contrasts from the available ones. Nevertheless, synthesizing 3D MRI presents significant challenges. Due to the massive volume sizes, operating directly in the pixel space is computationally prohibitive; therefore, a common approach is to first compress the 3D volumes into a latent space and subsequently train generative models in that space. We observe that existing compression architectures face several critical issues: they under-preserve long-range anatomical coherence, discard clinically meaningful semantics, and rely on optimization objectives that lead to over-smoothed reconstructions. Ultimately, these shortcomings compromise the performance of subsequent generative models. In this work, we propose a semantics-first latent modeling framework for 3D MRI reconstruction and cross-contrast synthesis. Specifically, we introduce a Latent Harmonization Encoder (LHE) to capture global anatomical dependencies, ensuring coherent volumetric representations. To mitigate semantic degradation during latent compression, we further design a Semantic Recovery Block (SRB) that injects high-level priors from a self-supervised semantic teacher, enhancing contrast-aware separability in the latent space. Additionally, we propose an Anatomy-aware Frequency Loss (AFL) to adaptively preserve diagnostically relevant high-frequency structures. Extensive experiments on two public multi-contrast MRI datasets demonstrate consistent improvements in reconstruction fidelity and cross-contrast synthesis quality. Our code is available at https://github.com/script-Yang/RSF.

Whole-brain 4D fMRI generation is valuable for modeling functional brain dynamics, yet existing fMRI foundation models mainly target representation learning and downstream prediction rather than conditional predictive generation. We introduce BrainWorld, a structural-prior-conditioned generative model for whole-brain 4D fMRI dynamics. BrainWorld uses sMRI as subject-level anatomical context to guide future fMRI generation, integrating structural information into the denoising process rather than treating it as a parallel modality. Evaluated on 22 datasets spanning diverse cohorts and brain states, BrainWorld generates stable 4D fMRI trajectories up to 400 frames, improves downstream performance through generated-example augmentation, and learns transferable multimodal representations that outperform baselines. Together, these results establish BrainWorld as a condition-aware generative framework for long-horizon brain dynamics modeling and multimodal representation learning.

Magnetic resonance imaging-signal fat fraction (MRI-SFF) quantifies tissue fat and serves as an established biomarker for metabolic and musculoskeletal disorders. The acquisition requires, however, specialized MRI sequences, which are not available routinely. We investigate whether SFF can be estimated from widely available T2-weighted (T2w) MRI via image-to-image translation (I2I). We further compare a lightweight 4-level U-Net to a state-of-the-art Denoising Diffusion Probabilistic Model (DDPM) using a dataset of 230 048 paired 2D images (183 517 train, 23 621 val, 22 910 test) from the German National Cohort (NAKO). Both models clearly outperform the identity baseline (Pearson correlation r = 0.769, mean absolute error MAE = 0.070 +/- 0.054), which confirms that the models learn a non-trivial cross-modal mapping. Interestingly, the lightweight U-Net outperforms the DDPM in both correlation (r = 0.975 vs. 0.962) and error (MAE = 0.014 +/- 0.015 vs. 0.019 +/- 0.019), while reducing inference time by a factor of 208 (25.2 ms vs. 5 227.2 ms per image using 50 Denoising Diffusion Implicit Model (DDIM) steps). The strong clinical performance at substantially reduced computational cost enables real-time clinical use.

This work addresses the computational problem of generating reproducible projection-space observations from heterogeneous anatomical scenes whose components may undergo independent spatial transformations. We propose a transformation-driven framework for synthetic projection imaging from multimodal anatomical data and demonstrate it on mandibular-motion scenarios. In contrast to conventional Digitally Reconstructed Radiograph (DRR) approaches primarily designed for registration, projection realism, or rendering efficiency, the proposed formulation treats projection imaging as an observation process operating on an explicitly represented anatomical scene. Independently transformable volumetric and surface-based anatomical objects are embedded within a shared scene representation and propagated directly into projection space through explicit transformations. Projection geometry, acquisition modelling, material interpretation, and image presentation remain explicitly separated, enabling controlled exploration of methodological assumptions while preserving reproducibility and direct comparability between generated projections. Particular emphasis is placed on transformation-driven anatomical scenarios relevant to craniofacial analysis, including mandibular motion and therapeutic repositioning. Using a shared anatomical reference scene composed of CT/CBCT volumes, segmented structures, surface models, and auxiliary anatomical or therapeutic objects, the framework enables generation of directly comparable VirtualRTG projections from multiple anatomical configurations while preserving identical imaging assumptions. Rather than aiming at fully physically faithful radiographic simulation, the proposed approach provides a controllable and reproducible methodological environment for studying anatomy--projection relationships, motion observability, and transformation-aware imaging workflows.

Fundus fluorescein angiography (FFA) is critical for assessing retinal vascular abnormalities, but its acquisition is invasive and not always feasible. In contrast, color fundus photography (CFP) is non-invasive and widely accessible, which has motivated studies on CFP-to-FFA synthesis. However, prior works rely solely on CFP surface texture, fundamentally limiting the ability to reconstruct functional vascular information and subtle pathological changes. To address this, we propose a novel framework that synthesizes FFA from CFP with structural guidance provided by optical coherence tomography (OCT). We construct a multi-modal retinal imaging dataset with paired CFP, FFA, and OCT from 3,676 patient eyes--the first tri-modally aligned dataset in retinal imaging. To bridge the spatial gap between OCT and fundus modalities, we propose a Spatially Aligned Cross-Modal Fusion (SACMF) module that projects depth-resolved OCT features onto the fundus plane and injects them into the CFP encoder via adaptive layer normalization. Beyond feature fusion, we further introduce Token-wise Cross-Modality Alignment (TCMA), a token-level contrastive learning strategy that explicitly aligns CFP and FFA representations at corresponding spatial positions. Our method achieves superior synthesis performance compared to state-of-the-art methods. Moreover, extensive experiments demonstrate that the FFA images synthesized by our approach bring greater improvements in downstream disease diagnosis performance than existing methods, highlighting the clinical potential of our approach as a non-invasive decision-support tool in routine workflows. The code is available at https://github.com/while-plus/OCT-guide-FFA-Syn.

3D FLAIR MRI is widely recommended as one of the standard MRI sequences for brain imaging in multiple sclerosis (MS), but publicly available MS datasets remain relatively small and vary across scanners, acquisition protocols, and lesion patterns. This scarcity and variability hinder the development of robust neuroimaging machine learning models and are particularly challenging for generative models that aim to synthesize images while preserving small, sparse lesions. We propose Lesion-DDPM, a 3D conditional diffusion framework for lesion-aware FLAIR synthesis that incorporates multi-level anatomical mask injection together with a lesion-weighted reconstruction loss to emphasize lesion voxels while maintaining global brain structure. Using a curated subset of the MSLesSeg dataset, we compare Lesion-DDPM with representative state-of-the-art GAN- and diffusion-based models, assessing both image-generation metrics and downstream 3D U-Net segmentation. In our experiments, Lesion-DDPM achieved the lowest lesion-region reconstruction error among all methods. In a downstream 3D U-Net lesion segmentation task, a model trained only on Lesion-DDPM-generated scans and evaluated on real MRIs reached a Dice score of 0.616 compared with 0.569 for the best competing synthetic dataset. When Lesion-DDPM images were added to the real training set, the Dice score further increased to 0.685.

Hematoma expansion (HE) after spontaneous intracerebral hemorrhage (ICH) is a major determinant of acute triage and treatment decisions in neurosurgical care. However, most existing methods provide either a binary expansion risk or a single follow-up volume, limiting uncertainty-aware decisions. We introduce HemExp, a clinically-guided latent diffusion model that generates patient-specific follow-up non-contrast CT images, along with segmentations of intraparenchymal and intraventricular hemorrhage. Generation is conditioned on baseline imaging, clinical variables, and an explicit expansion indicator, enabling controllable simulation of realistic clinical scenarios. HemExp uses a hemorrhage-aware multi-head variational autoencoder and models progression as the difference between baseline and follow-up latent representations with a conditional diffusion model. The model is trained on paired scans from 450 patients across multiple centers and evaluated on 107 patients from a held-out institution. HemExp produces spatial HE probability maps by generating multiple synthetic follow-up images per patient to estimate distributions of plausible follow-up hematoma volumes. Perturbing clinical inputs such as symptom-onset-to-imaging time or anticoagulant status shifts the predicted follow-up volume distribution. HemExp extends binary predictors and demonstrates robust estimation of clinically relevant outcomes in the imaging space, such as hematoma volume, intraventricular involvement, and mass effects. Overall, our results support controllable latent diffusion as a promising direction for uncertainty-aware modeling of early ICH progression.

We present a Dual-Domain Equivariant Generative Adversarial Network (DDE-GAN) for multimodal CT-PET image synthesis. Traditional GAN-based approaches often operate solely in the spatial domain and ignore geometric consistency, resulting in limited structural fidelity. DDE-GAN addresses these challenges by jointly learning from both spatial and frequency (Fourier) domains, capturing complementary anatomical and spectral information. Furthermore, rotational equivariance embedded in the physics of the CT and PET measurements are integrated into the loss of both the generator and discriminator to ensure consistent responses under rotations, improving anatomical accuracy. A hierarchical dual-domain training strategy enforces intra- and inter-domain consistency through multi-stage loss functions. Evaluated on the HECKTOR 2022 CT-PET dataset, DDE-GAN achieves superior synthesis quality over baseline models for CT-PET image synthesis. The results demonstrate that combining dual-domain learning with geometric equivariance substantially enhances multimodal image synthesis accuracy and robustness, enabling practical applications in PET completion and data augmentation.

Multi-modal MRI brain image translation via available modalities holds significant practical importance in modern medicine, providing robust support for early diagnosis, treatment planning, and outcome assessment of diseases. For this purpose, it is important to ensure the fidelity of the tumor regions after translation. However, existing brain image translation methods ignore the structure information of different tumor regions, which could assist translation models in enhancing the quality and clinical applicability of the translated images. In this work, we propose a novel translation model called HTSCGAN, which is a unified multi-modal brain image translation generative adversarial model integrating the structural information within tumor regions with the aim of improving the quality of brain image translation. Specifically, the generator employs three Patch Contrast Module (PCM) with different patch sizes to capture the hierarchical structural information of the tumor regions. In addition, a pretrained Patch Classifier (PC) and a pretrained Structure-Aware Encoder (SAE) are employed to derive the generated image containing the same tumor region structure as the ground truth image via patch classification loss and tumor perceptual loss, respectively. The experiments on BraTS2020 and BraTS2021 demonstrate strong performance of our model in both translation tasks and down stream segmentation tasks, highlighting its effectiveness in enhancing the quality and clinical relevance of the translated brain images. Our code is available at https://anonymous.4open.science/r/HTSCGAN.

Diffusion models have become essential for high-fidelity 3D MRI synthesis, yet their deployment remains constrained by substantial GPU resource demands arising from hundreds of U-Net evaluations per sample and a highly heterogeneous kernel behavior. This paper performs a comprehensive performance analysis of the state-of-the-art medical diffusion model, Med-DDPM, across three generations of NVIDIA architectures to study kernel-level runtime breakdowns, instruction-mix characteristics, memory system utilization, warp-level activities, and profiler priority-score estimates. We show that training is overwhelmingly dominated by cuDNN convolution and implicit-GEMM kernels, with inefficiencies arising from memory-access patterns, tensor-layout conversions, and limited Tensor Core utilization. Guided by these insights, we evaluate two architecture-aware optimizations TF32 Tensor Core activation and a 3D channels-last layout and demonstrate that they reduce SM cycles by up to 100x, cut dynamic instructions by 100x, raise Tensor Core utilization from 1.45 to 9.98x, and increase IPC by 7% on A100, all without degrading synthesis quality.

Cine cardiac magnetic resonance is the gold standard for assessing cardiac function, but the scarcity of public datasets limits the development of advanced data-driven models. To address this limitation, we propose a generative method for synthesizing temporally coherent and anatomically consistent cardiac sequences. Our text-to-video framework decouples cardiac spatial structure from temporal motion. First, a fine-tuned diffusion model synthesizes an initial frame from a clinical text prompt, controlling anatomical features. Then, a latent flow model conditioned on a cardiac phase embedding generates the complete cardiac motion, ensuring spatial consistency and temporal control. Our model generates anatomically and pathologically diverse sequences with high temporal coherence and strong fidelity to input prompts, achieving a FID of 31.68 for image realism and a CLIP score of 31.04 for text-image alignment. These experimental results highlight its potential to produce high-fidelity, on-demand medical data, offering a scalable solution to data scarcity.

Large and demographically balanced datasets are essential for reliable neuroimaging biomarkers. Full-resolution 3D brain MRI synthesis can support data augmentation in this setting, but existing approaches either incur prohibitive computational cost at volumetric scale or rely on lossy latent compression that may compromise anatomical detail. As a result, practical 3D generative augmentation often requires specialized compute infrastructure. We propose WaveDiT, a conditional flow matching framework operating in the coefficient space of a 3D Haar Discrete Wavelet Transform. The model combines factorized spatio-depth attention with band-wise heteroscedastic uncertainty modeling derived from higher-order wavelet statistics. Predicted log-variance is integrated directly into both the flow objective and conditioning pathway, enabling adaptive precision consistent with the heavy-tailed and input-dependent variance structure of anatomical detail. This formulation supports full-resolution 3D synthesis under practical memory and time constraints on a single modern GPU. Evaluation on a multi-site cohort demonstrates improved alignment between generated and real MRI distributions, together with enhanced downstream brain age prediction and region-level anatomical agreement relative to diffusion, latent, and wavelet-based baselines. Code is available at https://github.com/sisinflab/WaveDiT

Multi-contrast brain MRI provide complementary soft-tissue characteristics that aid in the screening and diagnosis of diseases. However, limited scanning time, image corruption and various imaging protocols often result in incomplete multi-contrast images. While current approaches excel in image synthesis, they often struggle to synthesize critical tumor regions and exploit contextual information in multi-contrast brain MRI effectively. To address this issue, we propose a synthesis-centric, segmentation-assisted closed-loop framework with retrieval augmentation synthesis. Our method overall takes a generative adversarial architecture, which aims to synthesize missing contrasts from any combination of available ones with a single model. To explicitly capture tumor semantics and focus synthesis on tumor regions, we add an auxiliary segmentation branch that predicts tumor masks and feeds them back as semantic conditioning in synthesis branch, thereby learning tumor-aware representations in the model and improving synthesis fidelity. Furthermore, we propose a dual-bank retrieval augmentation strategy. It dynamically queries two external knowledge bases, namely a tumor masks memory bank for crucial tumor context and cross-image contrast feature memory bank for global style information, to augment synthesis. Verified on two public multi-contrast magnetic resonance brain datasets: BraTs2020 and UCSF-BMSR, the proposed method is effective in handling medical brain images synthesis tasks and shows superior performance compared to previous methods. Code is available at:https://github.com/iBizzard/SSCF.git

Background and Purpose: Automated detection of focal cortical dysplasia (FCD) requires large volumes of voxelwise lesion-delineated MRI data, which are difficult to acquire. This study aims to generate synthetic MRI data exhibiting FCD, assess their realism, and evaluate their impact on automated FCD detection, particularly in reducing the need for manual annotations. Methods: T1-weighted (T1w) and T2-weighted Fluid-Attenuated Inversion Recovery (FLAIR) MRI scans from 131 FCD patients and 90 healthy controls from multiple (3) sites were retrospectively studied. Synthetic MRIs were generated by conditioning a generative network on binary FCD masks. Two neuroradiologists identified real images from a random set of 14 real and 14 synthetic scans. Three nnU-Net models were trained to detect FCD using: (i) real-only (35 FCD / 35 controls), (ii) real (35 FCD / 35 controls) plus synthetic augmentation, and (iii) expanded real data (70 FCD / 70 controls). Results: Experts showed limited ability to distinguish real from synthetic images, with classification accuracy of 60% for T1w and 70% for FLAIR (inter-rater agreement kappa = 0.86). Augmenting automated FCD detection with synthetic data increased sensitivity by 8.14% (p = 0.12) and improved model confidence at true lesion sites (0.83 +/- 0.11 to 0.89 +/- 0.12; p = 0.02). The expanded real-data model further improved sensitivity to 73.8% (p < 0.001) and confidence to 0.90 +/- 0.14 (p = 0.01). Conclusion: Conditional generative networks can generate realistic synthetic FCD-MRIs, reducing labeled data needs by approximately 20% while maintaining equivalent sensitivity. Equivalent amounts of real data, when available, remain more effective than synthetic augmentation.

Synthetic histopathology image generation addresses patient-privacy concerns and the growing data demands of foundation models. Existing state-of-the-art histopathology generative models use pretrained Vision Foundation Models (VFMs) as conditioning signals. We show this yields conditioning-dominated diversity: on TCGA-BRCA, 62-75% of their output diversity is attributable to the conditioning signal rather than the learned latent space, while de novo synthesis still requires a VFM at inference. We instead use histopathology VFMs as the latent space itself: their patch tokens are $\ell_2$-normalized on the unit hypersphere $\mathcal{S}^{d-1}$ with strong angular dominance and intrinsic curvature, motivating a Riemannian formulation. We present STREAM, the first framework to apply Riemannian flow matching in the histopathology domain, in two stages: 1) a bridge-type stochastic perturbation that establishes per-token rectifiability on $\mathcal{S}^{d-1}$ for training a Diffusion Transformer, and 2) a novel decoder training design whose noise covariance is anisotropic in the left-singular basis of the per-token tangent-projected velocity-field Jacobian, spending a large robustness budget on its low-response directions and a small one on its high-response directions. Across TCGA-BRCA and TCGA-COADREAD, STREAM achieves state-of-the-art gFID and ranks first on nearly all histopathology-specific metrics as well. Code and a public gallery of generated images are available at https://chokevin8.github.io/STREAM-Patho/.

Maximal safe resection is the primary objective in glioma surgery. Neuronavigation guidance is progressively degraded by brain shift after dural opening. Intraoperative MRI can compensate but needs dedicated infrastructure and is rarely available, whereas intraoperative ultrasound (ioUS) is inexpensive, repeatable, and compatible with routine workflows. Navigation systems combining ioUS with preoperative MRI usually rely on rigid registration; even deformable multimodal registration is limited by ultrasound speckle contrast, a narrow field of view, and the inability to represent structures absent from the preoperative scan, most critically the resection cavity and residual tumor. We propose an end-to-end pipeline that generates a new whole-brain MRI volume in the preoperative imaging space by merging the preoperative MRI, a synthetic MRI generated from the ioUS, and a deformable registration anchored on that synthetic image. It integrates a 2.5D residual-transformer synthesis backbone (ResViT-2.5D) and a two-stage registration coupling NiftyReg with a synthesis-anchored SynthMorph stage, operating directly on raw scanner inputs. On a post-resection ReMIND cohort, ResViT-2.5D produced synthetic images closely matching the intraoperative T2 across structural, intensity, and perceptual metrics. In 14 subjects with 215 expert landmarks, the synthesis-anchored registration reduced the mean target registration error from 6.27 to 5.86 mm, matching a strong classical NiftyReg baseline (5.85 mm) while yielding a diffeomorphic deformation field in every subject. The contribution is not a gain in registration accuracy but the integrated volume itself, which inside the ultrasound field of view it reflects the intraoperative post-resection state. This provides the surgeon with an MRI-like update of the operative field with potential for integration into surgical-navigation workflows.

Medical imaging is central to modern diagnostics, and artificial intelligence (AI) systems are increasingly used to support image-based analysis by improving efficiency, accuracy, and access to care. However, inequities in healthcare access and differential disease prevalence create severe demographic imbalances in clinical image data. Such imbalances are compounded by the fact that diseases can manifest with distinct features across demographic groups, rendering certain phenotypic presentations naturally rare. AI models trained on such imbalanced data risk perpetuating diagnostic bias and widening healthcare disparities. Here we introduce FairGen, a fairness-aware diffusion framework that synthesizes demographically balanced medical images while preserving pathology-relevant visual features. By embedding physician-aligned preferences into the generation process, FairGen improves subgroup coverage during synthesis and downstream classification. Applied to dermatology, radiology, and neuroimaging benchmark tasks, FairGen achieves fairness improvements of 95.9% for skin images, 80.0% for chest radiography, and 35.2% for brain MRI, while maintaining competitive diagnostic accuracy relative to models trained on original clinical data. Clinician-facing expert review and external validation on independent cohorts further support that these gains extend beyond standard fidelity metrics and are not confined to the original in-distribution datasets.

This study investigates the trade-offs between fidelity, privacy, and utility in synthetic data generation under conditions of data scarcity and privacy sensitivity. We propose an evaluation framework that jointly assesses these three dimensions and apply it to three widely used generative models, VAE, GAN, and DDPM. The evaluation spans three image datasets, MNIST, OCTMNIST, and OrganAMNIST, encompassing both general-purpose and medical imaging domains. Notable differences arise between the three models in their behaviour when differential privacy mechanisms are introduced during training. GAN and DDPM demonstrate greater robustness, maintaining higher fidelity and downstream utility across a range of noise levels, while VAE degrades more rapidly as privacy constraints increase. This study highlights the importance of a multidimensional evaluation of deep generative models, also noting that their behaviour significantly differs when privacy techniques are applied.

Immunohistochemistry (IHC)is frequently used to resolve diagnostically ambiguous prostate cancer biopsy findings on hematoxylin and eosin (H&E)-stained tissue. However, PIN-4 IHC staining is typically performed on adjacent tissue sections, limiting direct spatial comparison between the H&E morphology and the corresponding immunophenotypic signal. A paired, registered H&E/PIN-4 dataset was constructed from routine clinical prostate biopsy whole-slide images (WSIs), and a conditional generative adversarial network (cGAN) was trained to synthesize PIN-4 staining patterns directly from native H&E image patches. The final dataset comprised 172 paired WSIs from 93 patients and 27,298 registered 1024x1024 patch pairs, spanning adenocarcinoma-positive and benign cases with representation across age, race, and ethnicity groups. The model was evaluated on a held-out test set of 1,814 patch pairs from 17 WSIs, achieving a mean peak signal-to-noise ratio (PSNR) of 21.88 dB, structural similarity index measure (SSIM) of 0.667, Pearson correlation coefficient (PCC) of 0.684, and learned perceptual image patch similarity (LPIPS) of 0.417. Qualitative review by a board-certified pathologist showed that generated images captured diagnostically relevant PIN-4 staining patterns, including AMACR/racemase expression and basal-cell-associated staining, while preserving spatial correspondence with the source H&E morphology. Accuracy of synthesis varied across morphologically complex regions, including high-grade carcinoma and intraductal carcinoma. These results support the feasibility of supervised PIN-4 synthesis from routinely acquired brightfield H&E prostate biopsy images. The approach enables direct interpretation of predicted PIN-4 marker patterns in the context of the source prostate H&E architecture, addressing a current spatial limitation of conventional adjacent-section IHC.

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.