Medical Image Synthesis

MRI sequence synthesis aims to recover missing image contrast while preserving patient-specific anatomy. The choice of generation mechanism affects both optimization and the way source information reaches the synthesized image. In this study, we propose SRUG, a supervised standalone fusion-driven generator that learns a deterministic source-to-target mapping for paired MRI synthesis. Its direct reconstruction formulation removes generator-discriminator competition and requires neither variational latent sampling nor iterative diffusion denoising. To support structural fidelity within this formulation, SRUG uses a residual encoder adapted for image reconstruction, with a full-resolution convolutional stem, pooling-separated feature stages, and channel recalibration embedded in the residual branches. A nested multi-scale decoder (NMD) repeatedly fuses the resulting spatial features and predicts the target sequence through a single output head. L1 loss and Multi-Scale Structural Loss (MSS loss) jointly supervise the prediction, connecting the direct generation objective to anatomical detail recovery. Experiments on BraTS 2023 show competitive reconstruction fidelity and structural consistency across three MRI translation tasks. Architecture ablations assess the effects of channel recalibration, NMD, and structural supervision within the same generator framework. Additional evaluation on IXI supports applicability to another dataset and modality pair, while zero-shot testing on BraTS 2019 provides preliminary evidence of cross-dataset transferability. These results support direct supervised generation as a practical approach to paired MRI sequence synthesis, with the adapted encoding and reconstruction pathway providing the basis for structural preservation. The SRUG implementation is publicly available at https://github.com/RisingRich/SRUG.

Synthetic medical image data can unlock the potential of deep learning (DL)-based clinical decision support (CDS) systems through the creation of large scale, privacy-preserving, training sets. Despite the significant progress in this field, there is still a largely unanswered research question: "How can we quantitatively assess the similarity of a synthetically generated set of images with a set of real images in a given application domain?". Today, answers to this question are mainly provided via user evaluation studies, inception-based measures, and the classification performance achieved on synthetic images. This paper proposes a novel measure to assess the similarity between synthetically generated and real sets of images, in terms of their utility for the development of DL-based CDS systems. Inspired by generalized neural additive models, and unlike inception-based measures, the proposed measure is interpretable (Interpretable Utility Similarity, IUS), explaining why a synthetic dataset could be more useful than another one in the context of a CDS system based on clinically relevant image features. The experimental results on publicly available benchmark datasets from various color medical imaging modalities including endoscopic, dermoscopic and fundus imaging, indicate that selecting synthetic images of high utility similarity using IUS can result in relative improvements of up to 54.6% in terms of classification performance. The generality of IUS for synthetic data assessment is demonstrated also for grayscale X-ray and ultrasound imaging modalities. IUS implementation is available at https://github.com/innoisys/ius.

Text-to-image flow matching transformers degrade sharply in long-tail settings: tail-class outputs collapse in fidelity and diversity, limiting their value as synthetic augmentation for rare conditions. We trace this to low head-versus-tail gradient alignment during fine-tuning, an optimization-level pathology that conditioning- and sampling-side interventions do not address. We propose GRASP (Guided Residual Adapters with Sample-wise Partitioning): a deterministic partition of the conditioning space, paired with group-specific residual adapters in the transformer feedforward layers, that leaves the flow-matching objective and the sampler untouched. In conditional flow matching, condition values index distinct sets of probability paths, which makes the conditioning a structurally natural axis along which to factorize residual updates. Because the partition is static, every tail sample is guaranteed to update its assigned expert, which bypasses extreme long-tail failure modes. GRASP is non-invasive and composable: on MIMIC-CXR-LT, combining GRASP with self-guided minority sampling at inference outperforms its learned counterpart on 10 of 12 metrics. Performance is stable across random reassignments of labels to experts and across expert counts, as long as no expert is starved of samples. Used as training data for a downstream DenseNet classifier on NIH-CXR-LT, GRASP synthetics significantly outperform every non-GRASP alternative on macro F1 and yield nonzero F1 on 9 of 13 classes versus 3 of 13 from real data, while maintaining comparable macro F1. Results on ImageNet-LT confirm the mechanism is not tied to medical inductive bias. Code is available at https://github.com/Felix-012/GRASP-LT

Brain tumors induce complex structural deformations that obscure the patient' s original neuroanatomy, making it difficult to distinguish tumor-induced changes from inherent anatomical variability. Reconstructing a subject-specific pseudo-healthy brain can provide a critical reference for such analysis, but this task is inherently counterfactual, as paired pre-tumor scans and explicit healthy guidance are unavailable. We propose BrainNormalizer, a diffusion-based framework for subject-specific pseudo-healthy brain MRI reconstruction that enables anatomy-informed reconstruction without requiring paired data or explicit healthy references. The framework learns anatomical priors and edge-based structural conditioning through a two-stage training strategy consisting of inpainting-based diffusion fine-tuning and ControlNet-based edge conditioning. At inference, counterfactual pseudo-healthy reconstruction is achieved through a deliberate misalignment strategy, where tumorous inputs are paired with non-tumorous prompts and mirrored contralateral edge maps. This allows subject-specific anatomical guidance to be constructed from the patient's own anatomy, enabling anatomically consistent pseudo-healthy reconstruction that preserves individual structural characteristics. Experiments on the BraTS2020 dataset demonstrate that BrainNormalizer achieves improved distributional realism, symmetry-based structural consistency, and reduced false positive detection compared to existing methods. These results indicate that the proposed framework provides a principled approach for subject-specific counterfactual reconstruction and supports downstream analysis of tumor-induced deformation.

Generative modeling frameworks have emerged as an effective approach to capture high-dimensional image distributions from large datasets without requiring domain-specific knowledge, a capability essential for disease progression modeling. Recent generative approaches have attempted to capture progression by mapping images to a latent space and guiding representations to generate follow-up images from previous time points. However, these methods impose constraints on distribution learning, resulting in latent spaces with limited controllability for generating follow-up images without paired subject-specific longitudinal guidance. In order to enable controlled movements in the latent representational space and generate progression images from a previous time-point image without subject-specific guidance, we introduce a conditionable Diffusion Auto-encoder framework that forms a compact latent space capturing high-level semantics and providing means to control generation. Our approach leverages this latent space to condition and apply controlled shifts to the representations of previous time-point images by isolating progression and subject identity information for generating follow-up images. The shifts are implicitly guided by correlating with progression attributes and constraining to Alzheimer's disease specific regions, without paired longitudinal guidance. We validate the generations through image quality metrics, volumetric progression analysis, and downstream tasks in Alzheimer's disease datasets from different sources. This demonstrates the effectiveness of our approach for Alzheimer's progression modeling and longitudinal image generation.

This work introduces MedForj, a suite of 3D foundational generative priors based on diffusion models. The MedForj models were trained on $72{,}659$ 1~mm isotropic 3D $T_1$-weighted MRI human brain image volumes from $38{,}174$ subjects, drawn from a curated corpus of $80{,}675$ volumes from $42{,}506$ subjects spanning $38$ publicly available datasets. These training images were manually inspected to exclude those with poor quality and excessive pathology, and otherwise were minimally processed. The models include six different diffusion training strategies: rectified flow, latent diffusion rectified flow, flow matching, velocity prediction, clean prediction, and noise prediction. Image samples produced by each of these models were compared to each other and against real, ground truth data under downstream segmentation distributions, FID, five inverse problems, and blind human inspection in an observer study. Flow matching was the strongest strategy overall, achieving the best inverse problem solving results at $28.80$~dB PSNR and $0.874$ SSIM averaged over the five forward problems, the highest rate of reconstructions judged real by blind human raters at $72.6\%$, and the closest per-structure match to real segmented anatomy in a permutation test. It was not best everywhere: rectified flow produced the most convincing unconditional samples in the observer study and the best FID, and the latent rectified-flow model achieved the smallest joint distributional distance to real anatomy. No other strategy, however, performed consistently well across all four evaluations. We therefore recommend flow matching as the default MedForj prior, while releasing every strategy so that the choice can be revisited per application. All model weights and corresponding code are publicly available at https://github.com/piksl-research/medforj.

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.

Interest in generating realistic synthetic medical images has grown in recent years. Such datasets can mitigate the scarcity of public data for artificial intelligence research and support education. Work on synthesizing dental panoramic radiographs (PRs) has so far relied almost exclusively on generative adversarial networks (GANs), and three limitations recur: the synthesized field of view is often restricted to a cropped dentoalveolar region rather than a complete PR; observer studies of GAN-generated PRs report that clinicians still identify synthetic images with accuracies of roughly 78-82%, implying persistent visible giveaways; and adversarial training remains sensitive to instability and mode collapse. Generating a full-size PR directly at diagnostic resolution with a diffusion model is an alternative, but sampling at that resolution is costly. We therefore present PanoDiff-SR, an end-to-end two-stage pipeline developed and evaluated specifically for panoramic radiography: a denoising diffusion implicit model (PanoDiff) generates a low-resolution (LR) seed PR ($256\times128$), which a fine-tuned hybrid attention transformer (HAT) super-resolution (SR) stage upscales to a high-resolution (HR) PR of $1024\times512$. Decoupling the expensive generative step from the resolution step yields complete, full-arch PRs at diagnostic resolution on a single 47 GB GPU. The Fréchet inception distance between 7243 real and synthetic HR images is 40.5. Inception scores were 2.68, 2.38, 2.90 and 2.98 for real HR, synthetic HR, real LR and synthetic LR images, respectively. Six clinical experts, each evaluating 100 synthetic and 100 real PRs under a time limit, distinguished real from synthetic images with an average accuracy of 68.5% (50% corresponds to random guessing), substantially closer to chance than reported for GAN-based studies. Project page: https://s4nyam.github.io/panodiff/

Generating semantically controllable 3D CT volumes from radiology reports requires more than a rich text encoder, it requires vision-language alignment grounded in volumetric space. Existing Text-to-CT approaches condition generation on encoders pretrained with language only or 2D vision-language objectives, providing conditioning signals that are linguistically expressive but volumetrically blind. We argue this is a structural limitation: the quality of 3D vision-language alignment, not the richness of the text encoder, is the primary bottleneck for semantic controllability in volumetric diffusion models. To address this, we propose a generation-oriented 3D-CLIP encoder trained with structured hard negatives that operate exclusively at the text level. This design increases contrastive difficulty without any additional 3D memory cost, overcoming the small-batch constraints inherent to volumetric encoders. The resulting encoder conditions a fully end-to-end latent diffusion model that operates directly in 3D latent space, eliminating the spatial artifacts and cross-slice inconsistencies introduced by super-resolution pipelines. Through systematic ablations, we establish a clear empirical link between grounding quality and downstream generative controllability. Evaluated on CT-RATE across 18 pathological conditions, our method achieves state-of-the-art performance on both image fidelity and factual correctness, while requiring less inference time and GPU memory than all competing methods. Code is at https://github.com/danielemolino/Text2CT.

Medical imaging plays a vital role in clinical diagnosis, yet AI-driven imaging methods remain challenged by patient variability, image artifacts, and limited robustness across acquisition conditions. Although deep learning has advanced medical image analysis, 3D image translation remains hindered by limited training data and variability arising from scanner differences, imaging protocols, and patient motion. Conventional data augmentation typically relies on a single transformation pipeline, overlooking augmentation-specific characteristics and limiting representation learning. To address these challenges, we propose Multi-Encoder Augmentation-Aware Learning (MEAL), which processes multiple augmentation variants through dedicated encoder pathways. Three feature integration strategies are investigated: encoder concatenation (MEAL-CC), fusion layer (MEAL-FL), and an adaptive controller block (MEAL-BD). By dynamically weighting augmentation-specific features before decoding, MEAL-BD preserves complementary representations and improves robustness to clinically relevant variability. We evaluate MEAL using CT-to-T1-weighted MRI translation, a clinically relevant task when MRI is unavailable, contraindicated, or delayed. Across predefined and unseen test datasets, MEAL-BD consistently outperformed competing approaches under both geometric perturbations and standard imaging conditions, achieving higher peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM). By prioritizing structural fidelity over perceptual realism, MEAL supports clinical interpretation and downstream image analysis rather than replacing diagnostic MRI, demonstrating that augmentation-aware representation learning improves the robustness and clinical applicability of medical image translation.

Multi-modal medical image synthesis is pivotal for alleviating clinical data scarcity, yet existing methods fail to reconcile global anatomical consistency with high-fidelity local detail. We propose FermatSyn, which addresses three persistent limitations: (1) SAM2-based Prior Encoder that injects domain-aware anatomical knowledge via LoRA$^{+}$ efficient fine-tuning of a frozen SAM2 Vision Transformer; (2) Hierarchical Residual Downsampling Module (HRDM) coupled with a Cross-scale Integration Network (CIN) that preserves high-frequency lesion details and adaptively fuses global--local representations; and (3) continuity constrained Fermat Spiral Scanning strategy within a Bidirectional Fermat Scan Mamba (BFS-Mamba), constructing an approximately isotropic receptive field that substantially reduces the directional bias of raster or spiral serialization. Experiments on SynthRAD2023, BraTS2019, BraTS-MEN, and BraTS-MET show FermatSyn surpasses state-of-the-art methods in PSNR, SSIM, FID, and 3D structural consistency. Downstream segmentation on synthesized images yields no significant difference from real-image training ($p{>}0.05$), confirming clinical utility. Code is available at https://github.com/exsinger-hub/ FermatSyn.

Multi-contrast super-resolution (MCSR) is crucial for enhancing MRI but current deep learning methods are limited. They typically require large, paired low- and high-resolution (LR/HR) training datasets, which are scarce, and are trained for fixed upsampling scales. While recent self-supervised methods remove the paired data requirement, they fail to leverage valuable population-level priors. In this work, we propose a novel, decoupled MCSR framework that resolves both limitations. We reformulate MCSR into two stages: (1) an unpaired cross-modal synthesis (uCMS) module, trained once on unpaired population data to learn a robust anatomical prior; and (2) a lightweight, patient-specific implicit re-representation (IrR) module. This IrR module is optimized in a self-supervised manner to fuse the population prior with the subject's own LR target data. This design uniquely fuses population-level knowledge with patient-specific fidelity without requiring paired target-domain LR/HR training data or paired cross-modal HR reference-target training data. Here, 'unpaired' refers to the population-level training setting; at subject-specific inference, as in standard MCSR, the method uses a matched HR reference image from another contrast together with the subject's LR target image. By building the IrR module on an implicit neural representation, our framework is also inherently scale-agnostic. Our method demonstrates superior quantitative performance on different datasets, with exceptional robustness at extreme scales (16x, 32x), a regime where competing methods fail. Our work presents a data-efficient, flexible, and computationally lightweight paradigm for MCSR, enabling high-fidelity, arbitrary-scale reconstruction without the need for paired population-level supervision.