Evaluating Synthetic Data Generation for Domain Generalization in Fetal Brain MRI Segmentation
Authors: Vladyslav Zalevskyi, Thomas Sanchez, Margaux Roulet, Busra Bulut, Hélène Lajous, Jordina Aviles Verdera, Sara Neves Silva, Georg Langs, +5 more
Abstract
Fetal brain tissue segmentation from magnetic resonance imaging (MRI) is crucial for studying neurodevelopment, but remains challenging due to data heterogeneity and limited annotations. Domain randomization (DR) has recently emerged as a promising strategy for single-source domain generalization by synthesizing training images with randomized artifacts, contrast, and resolution. In this work, we investigate how to maximize the out-of-domain (OOD) generalization of DR-based methods. We evaluate several synthetic data generation strategies for DR, with a particular focus on our recently proposed framework, FetalSynthSeg. We show that simple Gaussian mixture-based intensity modeling outperforms more complex physics-based simulations, and that intensity clustering (subdividing tissue classes based on intensity) improves OOD robustness. Evaluated on 348 fetal subjects from four sites spanning 0.55-3T and both T1w and T2w contrasts, FetalSynthSeg reaches state-of-the-art performance on several FeTA 2024 testing datasets (80-85 Dice score) and, for the first time, offers robust segmentation on modalities other than T2w for fetal brain segmentation (80 Dice on dHCP-T1w dataset). Compared with state-of-the-art methods such as BOUNTI, nnU-Net ensemble, and the FeTA 2024 winner, FetalSynthSeg delivers comparable or superior accuracy while maintaining strong robustness across domain shifts. Our code, model weights, and Docker image ready for easy inference are available at https://hub.docker.com/r/vzalevskyi/fetalsynthseg.
Synthetic training has recently advanced brain MRI segmentation by enabling contrast-agnostic models trained entirely on generated data. However, most existing approaches rely on hundreds of automatically labeled templates, introducing systematic biases and limiting their flexibility to incorporate new anatomical structures. We present the Segment It All Model (SIAM), a 3D whole-head segmentation framework for 16 anatomical structures, trained using only six high-quality, manually annotated templates. SIAM extends domain randomization to both intensity and shape domains: synthetic image generation ensures contrast variability, while high-resolution spatial transformations model anatomical differences in cortical thickness and deep nuclei morphology. Unlike prior synthetic models, SIAM simultaneously segments brain as well as extra-cerebral tissues, including cerebrospinal fluid, vessels, dura mater, skull, and skin, enabling fully automated, preprocessing-free analysis. Evaluation across eight heterogeneous datasets (N=301), that include multiple contrasts (T1-weighted, T2-weighted, CT) and span a wide range of ages, demonstrates that SIAM matches or outperforms state-of-the-art methods for brain structures, in addition to extending automated segmentation to non-brain structures. The model also exhibits superior consistency across contrasts and repeated acquisitions, together with improved sensitivity to subtle gray matter atrophy. We openly release the model and the label templates at https://github.com/romainVala/SIAM.
Prenatal ultrasound imaging is key for assessing fetal health, but AI progress is limited by scarce, privacy-restricted, and hard-to-annotate datasets. We propose a high-resolution fetal ultrasound synthesis framework based on the EDM2 diffusion architecture, trained on multiple public datasets to generate 512x512 images across six anatomical classes. Our method achieved improved image quality with lower FID scores and enhanced downstream fetal plane classification, reaching 93.36% ensemble accuracy after fine-tuning, surpassing real-data-only training. Clinical evaluation by an experienced fetal ultrasound specialist (10+ years) on 100 images yielded a mean realism score of 2.67/5, with real images rated higher than synthetic. Artefacts included smoothing, speckle irregularities, and anatomical inconsistencies. Code, data, models and other resources to reproduce this work are available at https://github.com/xfetus/fetal-ultrasound-edm2.
Diffusion MRI (dMRI) tractography enables non-invasive reconstruction of white-matter pathways, but its accuracy is fundamentally limited by indirect, low-resolution measurements of axonal organization. Tracer injection studies in non-human primates provide a gold standard for validating dMRI tractography. This, however, requires time-consuming manual annotation of fiber bundles in histology sections. We propose a synthetic-data augmented framework for automated fiber bundle segmentation in macaque tracer histology. Our approach uses ex vivo dMRI tractography as a generative prior to synthesize 2D image patches for training. This provides us with sufficiently realistic foreground texture, which we compose with backgrounds from blockface photos and diversify via domain randomization. A 2D U-Net is trained on mixed real and synthetic patches. Experiments on held-out brains demonstrate improved generalization across brains and fiber bundle densities compared to training with real data only. Training with synthetic data only leads to poor performance, underscoring the need for real supervision. Overall, our approach achieves performance comparable to the state-of-the-art while requiring 3x less manually annotated data.