Medical Image Modality Translation

Missing modality imputation aims to synthesize unobserved modalities from observed ones. Existing methods treat each modality as living on its own latent manifold, forcing the generator to learn a long, unstructured jump between them. We present SphereFlow, which takes a fundamentally different view: by projecting all modalities into a shared hyperspherical latent space via a frozen self-supervised encoder, cross-modal imputation reduces to short-range geometric transport between nearby points on the sphere. Realizing this idea with flow matching, however, exposes two geometric conflicts: the standard Gaussian noise source is catastrophically mismatched with the unit-norm data manifold, and the linear interpolation path departs the sphere surface into a region where the decoder has no training signal. We resolve both with simple, geometry-aware modifications: replacing the noise source with the observed-modality latent so that the velocity field learns only the cross-modal displacement, and training the decoder with a time-weighted loss that extends its domain to the near-surface region traversed by the flow. We prove that this data-as-source formulation reduces the worst-case off-manifold deviation from a quantity that grows with the latent dimension to a small, dimension-independent bound governed by inter-modality similarity. Experiments on BraTS multi-modal MRI imputation and CT-MRI translation demonstrate state-of-the-art generation fidelity across all settings, while downstream brain tumor segmentation with our imputed data closes roughly eighty percent of the gap to the full-modality oracle. Code is available at https://github.com/WTHH031230/SphereFlow.

Novel imaging modalities promise improved diagnostics, but AI development is constrained by scarce training data. Inference-time domain transfer can address this by mapping novel modalities to established ones, enabling reuse of existing diagnostic models. However, this introduces hallucination risks, computational overhead, and regulatory complexity. Inspired by sim-to-real transfer, we propose training-time domain transfer, generating synthetic target-domain training data from archived routine samples to enable direct diagnosis on real inputs without inference-time generation. Using unstained prostate histopathology as a proof-of-concept, we compare this approach with inference-time virtual staining and conventional H&E-based cancer detection. Training-time transfer achieved higher concordance with the conventional benchmark than virtual staining for both raw (Cohen's $κ$=0.59 vs. 0.37; Gwet's AC1=0.73 vs. 0.29) and deparaffinized tissue ($κ$=0.66 vs. 0.61; AC1=0.73 vs. 0.64), supporting its potential for emerging diagnostic modalities.

Positron Emission Tomography (PET) provides important metabolic information for tumor detection and staging but remains significantly less accessible than Computed Tomography (CT) due to its high cost, infrastructure requirements, and reliance on injected radioactive tracers. CT-to-PET image translation using generative models aims to address this disparity, yet state-of-the-art diffusion-based methods are limited by the scarcity of paired training data. To overcome this, we propose a domain-adapted latent diffusion framework that transfers natural-image priors using a relatively small dataset of 21,930 paired CT/PET slices, incorporating a signed power transform to resolve extreme intensity sparsity in PET data. Compared to CPDM, a state-ofthe-art baseline for CT-to-PET image translation, our approach yields superior performance in pixel-wise reconstruction and localized tumor fidelity, demonstrating effective transfer of natural-image priors to the medical domain. We further provide a systematic analysis of evaluation metric reliability for sparse PET data, showing that standard full-image metrics can be misleading indicators of translated image quality, and propose background-filtered and mask-restricted metrics as more clinically meaningful alternatives.

Cross-modality medical image translation is challenged by anatomically inconsistent synthesis that can compromise clinical diagnosis. We propose StaX-Net, a Stackelberg interleaved asymmetric network that incorporates a partially coupled encoder-discriminator structure, and a 2D feature aggregation and spatial transformation (FAST) layer that distills target-supervised priors under the learning using privileged information paradigm. The shared blocks between the generator and discriminator enhance architectural feature alignment. To stabilize the leader-follower training, a Stackelberg-inspired asymmetric optimization scheme employs explicit shared-parameter freezing and asymmetric learning rates. The FAST layer distills target-domain priors during training and applies a source-only transform at inference. This constrains the synthesis process through target-informed feature representations relative to standard generative architectures. The code is available on GitHub for public use.

Inter-modality MRI translation aims to synthesize missing MRI modalities from available acquisitions, reducing the need for additional scanning while preserving clinically relevant anatomical information. However, existing image translation methods often learn intensity mappings without explicitly separating modality-invariant structural information from modality-specific appearance, which may lead to structural information loss or unrealistic image details. In this work, we propose S2T-Unet, a structure-to-style framework that explicitly models these two aspects. Specifically, vector quantization is introduced at the lower-level bottleneck to encode modality-invariant structural information using a learned discrete codebook. At higher levels, a modality transformation module uses decoder features to condition and transform encoder representations toward the target modality, thereby recovering modality-specific intensity and contrast information. Experiments on the IXI multi-contrast MRI dataset across four translation tasks demonstrate that S2T-Unet is comparable or outperform with state-of-art method.

Strongly paired medical image translation contains a substantial component that can be predicted directly from the source. The current reality is that pure deterministic prediction can smooth away fine detail, while generative models can recover detail but may also introduce unnecessary or potentially harmful variation. We propose PredRA, a fast framework that uses the deterministic prediction as a stable reference and further extracts additional deterministic components from the residual during generative refinement, thereby improving fidelity while maintaining perceptual quality. The goal is simple: we view the entire residual-based generative process as an optimization problem and derive a practical solution that recovers useful residual detail through controlled refinement while keeping the prediction close to the paired target. Mechanism studies further show that useful residual information follows structured patterns, but its usefulness is difficult to estimate reliably at the voxel level. We therefore globally control how much of the residual refinement is added to the deterministic prediction, thereby reducing the accumulation of unnecessary uncertainty. PredRA therefore combines deterministic component extraction with controlled stochastic refinement for fast, fidelity-preserving, and perceptually strong medical image translation. We validate the approach across multiple real-world datasets, showing that controlled refinement improves fidelity to the paired target compared with full residual refinement while retaining much of the perceptual benefit of generative modeling. PredRA achieves competitive or superior performance to substantially larger state-of-the-art models with 1.4-11.9x fewer total parameters and 3.1-26.2x fewer trainable parameters, while its 32-step flow sampler requires 31.25x fewer sampling steps than the matched 1000-step DDPM.

Cross-modality medical image translation can reduce the burden of multi-modal acquisitions, yet the field remains constrained by two coupled limitations: methods operate on 2D slices or 3D patches rather than whole volumes, and train a separate model for each translation task. Both stem from a single cause, the absence of a sufficiently strong volumetric prior, which forces generative models to learn anatomical appearance and cross-modality mapping simultaneously, an ill-posed problem at the scale of available paired datasets. We propose to decouple these objectives. A large-scale pretrained 3D variational autoencoder provides a compact latent representation of volumetric appearance, reducing translation to a conditional flow-matching problem. This compression makes whole-volume processing tractable, while a resolution-aware sampling strategy preserves native anatomical scale. We train a single model jointly across inter-modality (MRI$\to$CT, CBCT$\to$CT) and intra-modality (MRI$\to$MRI) tasks over three multi-center datasets. Across all tasks, whole-volume processing outperforms its patch-based counterpart, and the multi-task model matches task-specific baselines while replacing $N$ networks with one. Crucially, joint training unlocks capabilities inaccessible to task-specific approaches: zero-shot generalization to anatomical regions unseen during training, within 0.15 SSIM of the fully supervised model, and compositional cross-dataset translation along paths never directly supervised. These results suggest that combining a strong volumetric prior with multitask training is a scalable route toward synthesis systems that generalize beyond their training distribution. Code is available at https://github.com/arco-group/Whole-Volume-Latent-FM.

Magnetic resonance imaging comes in various modality contrasts that provide complementary anatomical and pathological information. Complete multimodal acquisitions are often unavailable due to time and protocol constraints. This leads to real-world datasets with missing modalities, where conventional medical image translation methods are typically limited to fixed source-target settings or require retraining for each observed source-target pair. We propose a unified framework that formulates missing-modality generation as a linear inverse problem under a joint distribution and solves it via posterior sampling with a flow matching model. By learning a joint prior over the complete modality set, our method can reconstruct arbitrary missing modalities at inference time by guiding the sampling trajectory to enforce measurement consistency with observed modalities. We further mitigate inter-modality error propagation in multi-target generation by adopting a many-to-one sampling strategy. Experiments on BraTS and IXI datasets show that our method achieves the best performance over baselines across most missing-modality scenarios. In downstream tumor segmentation, synthesized images from our method result in higher segmentation performance, indicating better preservation of clinically relevant structures.

We present Spectral Consistent Flow (SC-Flow), a 3D medical image translation framework with a single function evaluation (1-NFE) in the latent space. This approach reformulates medical image translation as a stochastic Brownian bridge process that directly constructs a mapping between source and target modalities by predicting the support regularized mean velocity field. To mitigate modality entanglement, over-smoothing, and artifacts induced by the implicit low-pass modulation of the latent average velocity, we introduce a Spectral Consistency Corrector that dynamically regularizes the evolution of the power spectral density via learnable frequency-domain gain modulation. This mechanism establishes an explicit bridge between spatial textures and spectral energy flow, enabling the model to recover fine-grained anatomical fidelity while maintaining global structural coherence. Extensive experiments on four datasets demonstrate that SC-Flow delivers significantly more accurate, consistent, and robust performance across various translation scenarios.

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.

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.

High-resolution 3D medical image generation remains challenging because fully volumetric models are computationally expensive, while efficient 2D slice generators often fail to preserve anatomical consistency across the third dimension. We propose LiFT, a framework for Lifted inter-slice Feature Trajectories that factorizes 3D volume synthesis into per-slice image generation and inter-slice trajectory learning. Rather than using a fully volumetric synthesis backbone, LiFT treats a volume as an ordered trajectory in feature space, capturing how anatomical structures appear, transform, and disappear across depth. We demonstrate the LiFT framework in both unconditional and conditional settings. In unconditional generation, a tri-planar drifting loss matches feature distributions between generated and real volumes across three orthogonal planes; in paired translation, a bidirectional $z$-context mixer trained with paired target supervision supplies through-plane coherence while preserving per-slice fidelity. We evaluate LiFT on BraTS 2023 for unconditional and missing-modality MR synthesis, and on SynthRAD2023 for MR-to-CT translation. LiFT achieves competitive image quality while retaining the efficiency of predominantly 2D synthesis, operating up to $390\times$ faster than a volumetric diffusion baseline and consistently improving through-plane coherence through explicit inter-slice modeling. These results establish lightweight inter-slice trajectory learning as an efficient approach to high-resolution 3D medical synthesis.

Magnetic Resonance Imaging (MRI), Computed Tomography (CT), and Positron Emission Tomography (PET) provide complementary information about tissues. Medical image-to-image (I2I) translation enables virtual scanning by synthesizing a target modality from a source one without requiring an additional acquisition. Despite growing interest, many methods operate on 2D slices, are evaluated on isolated tasks under different experimental settings, and lack clinically oriented assessment. This work presents a reproducible benchmark for 3D I2I translation in oncological imaging that compares seven generative models: three Generative Adversarial Networks (Pix2Pix, CycleGAN, and SRGAN) and four latent models (Latent Diffusion Model, Latent Diffusion Model+ControlNet, Brownian Bridge, and Flow Matching). The benchmark comprises 77 experiments across eleven configurations drawn from five datasets, covering three anatomical regions (head/neck, lung, and pelvis) and four translation directions (cone-beam CT to CT, MRI to CT, CT to PET, and T2-weighted MRI to T2-FLAIR). Under the evaluated configurations, SRGAN achieves the highest quantitative image fidelity across all tasks, while latent models perform less well, due to information loss introduced by the variational autoencoder. A tumor-level analysis reveals that all models struggle with small lesions and that, in CT to PET synthesis, models reproduce tumor shape more reliably than tracer uptake values. A Visual Turing test involving 17 physicians, including 15 radiologists, shows near-chance classification accuracy (56.7%), suggesting that experts struggle to distinguish real from synthetic volumes under the viewing conditions of the study. Expert preferences do not follow quantitative rankings, exposing a dissociation between quantitative metrics and clinical preference.

Diffusion models produce high-quality synthetic data but suffer from slow inference. We propose 3D Variable-Step Denoising Diffusion Probabilistic Model (VS-DDPM) a framework engineered to maintain generative quality while accelerating inference by several factors. We tested our approach on four tasks (missing MRI, tumor removal, MRI-to-sCT, and CBCT-to-sCT) within the BraTS2025 and SynthRAD2025 challenges. Designed for high efficiency under hardware and time constrains imposed by both challenges. VS-DDPM achieved state-of-the-art (SOTA) performance in missing MRI synthesis, yielding Dice scores of 0.80, 0.83, and 0.88 for the enhancing tumor, tumor core, and whole tumor regions, respectively, alongside a structural similarity index (SSIM) of 0.95. For MRI tumor removal, the model attained a root mean squared error (RMSE) of 0.053, a peak signal-to-noise ratio (PSNR) of 26.77, and an SSIM of 0.918. While the framework demonstrated competitive performance in MRI-to-sCT and CBCT-to-sCT tasks, it did not reach SOTA benchmarks, potentially due to sensitivities in data pre and post-processing pipelines or specific loss function configurations. These results demonstrate that VS-DDPM provides a robust and tunable solution for high-fidelity 3D medical image synthesis. The code is available in https://github.com/andre-fs-ferreira/SynthRAD_by_Faking_it.

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.