Few-Shot Distribution-Aligned Flow Matching for Data Synthesis in Medical Image Segmentation

Segmenting thin structures like infrastructure cracks and anatomical vessels is a task hampered by topology-sensitive geometry, high annotation costs, and poor generalization across domains. Existing methods address these challenges in isolation. We propose FMS$^2$, a flow-matching framework with two modules. (1) SegFlow is a 2.96M-parameter segmentation model built on a standard encoder-decoder backbone that recasts prediction as continuous image $\rightarrow$ mask transport. It learns a time-indexed velocity field with a flow-matching regression loss and outputs the mask via ODE integration, rather than supervising only end-state logits. This trajectory-level supervision improves thin-structure continuity and sharpness, compared with tuned topology-aware loss baselines, without auxiliary topology heads, post-processing, or multi-term loss engineering. (2) SynFlow is a mask-conditioned mask $\rightarrow$ image generator that produces pixel-aligned synthetic image-mask pairs. It injects mask geometry at multiple scales and emphasizes boundary bands via edge-aware gating, while a controllable mask generator expands sparsity, width, and branching regimes. On five crack and vessel benchmarks, SegFlow alone outperforms strong CNN, Transformer, Mamba, and generative baselines, improving the volumetric metric (mean IoU) from 0.511 to 0.599 (+17.2%) and reducing the topological metric (Betti matching error) from 82.145 to 51.524 (-37.3%). When training with limited labels, augmenting SegFlow with SynFlow-generated pairs recovers near-full performance using 25% of real annotations and improves cross-domain IoU by 0.11 on average. Unlike classical data augmentation that promotes invariance via label-preserving transforms, SynFlow provides pixel-aligned paired supervision with controllable structural shifts (e.g., sparsity, width, branching), which is particularly effective under domain shift.

Domain shift across imaging modalities and acquisition sites remains a significant barrier to the clinical deployment of segmentation models. Source-free unsupervised domain adaptation (SFUDA) addresses this by adapting a pretrained model to an unlabeled target domain without requiring access to sensitive source data. We introduce a novel SFUDA framework built on Symmetrical Flow Matching, a unified generative model that segments an input image and synthesizes a source-like image from a mask within the same learned flow. By initializing inference from a domain-agnostic Gaussian origin, the model preserves structural consistency across domains and grounds predictions in learned anatomy rather than shifted texture statistics. Our pipeline leverages this symmetry to generate reliable pseudo-labels and corresponding source-like synthetic images from unlabeled target data, creating a generative replay buffer that anchors source knowledge during a generative self-training stage that fine-tunes on a joint set of real target and synthetic source-like images. We evaluate on abdominal multi-organ and cardiac segmentation, covering cross-modality MRI<->CT shifts, and multi-site prostate segmentation. Our approach outperforms SFUDA baselines and is competitive with conventional UDA methods.

Flow-based image generators achieve strong semantic synthesis but still produce localized structural distortions, such as malformed hands and limbs. Existing post-training methods typically optimize global scalar rewards, which provide weak spatial credit assignment and may alter well-formed regions while correcting local defects. We present Diagnose-to-Generate (D2G), a grounded alignment framework that separates visual diagnosis from generative optimization. We construct Achilles-600K, a region-annotated dataset for structural anomalies, and train ARGUS through supervised cold-start and Region-Aware Group Relative Policy Optimization to predict anomaly categories and bounding boxes. These diagnoses are converted into confidence-weighted spatial rewards for our Patch-level Flow-GRPO. We further identify that global stochastic exploration can shift semantic regions across group rollouts, making patch-wise relative advantages spatially inconsistent. Our Trajectory-Preserving Stochastic Sampling (TPSS) anchors early denoising with deterministic ODE trajectories and introduces stochasticity only at later steps, thereby limiting intra-group spatial drift while retaining local exploration. Experiments on FLUX.1-dev and SD3.5 show improved structural fidelity with preserved FID and CLIP scores. Consistent gains under HumanRefiner, zero-shot GPT-4.1, and blinded human evaluation further demonstrate that the improvements extend beyond the training reward model.