Magnetic Resonance Imaging (MRI) of the fetal brain has become a key tool for studying brain development in vivo . Yet, its assessment remains challenging due to variability in brain maturation, imaging protocols, and uncertain estimates of Gestational Age (GA). To overcome these, brain atlases provide a standardized reference framework that facilitates objective evaluation and comparison across subjects by aligning the atlas and subjects in a common coordinate system. In this work, we introduce a novel deep-learning framework for generating continuous, age-specific fetal brain atlases for real-time fetal brain tissue segmentation. The framework combines a direct registration model with a conditional discriminator. Trained on a curated dataset of 219 neurotypical fetal MRIs spanning from 21 to 37 weeks of gestation. The method achieves high registration accuracy, captures dynamic anatomical changes with sharp structural detail, and robust segmentation performance with an average Dice Similarity Coefficient (DSC) of 86.3 % across six brain tissues. Furthermore, volumetric analysis of the generated atlases reveals detailed neurotypical growth trajectories, providing valuable insights into the maturation of the fetal brain. This approach enables individualized developmental assessment with minimal pre-processing and real-time performance, supporting both research and clinical applications.

Accurate tissue segmentation in fetal brain MRI remains challenging due to the dynamically changing anatomical anatomy and contrast during fetal development. To enhance segmentation accuracy throughout gestation, we introduced AtlasSeg, a dual-U-shape convolution network incorporating gestational age (GA) specific information as guidance. By providing a publicly available fetal brain atlas with segmentation label at the corresponding GA, AtlasSeg effectively extracted the contextual features of age-specific patterns in atlas branch and generated tissue segmentation in segmentation branch. Multi-scale attentive atlas feature fusions were constructed in all stages during encoding and decoding, giving rise to a dual-U-shape network to assist feature flow and information interactions between two branches. AtlasSeg outperformed six well-known segmentation networks in both our internal fetal brain MRI dataset and the external FeTA dataset. Ablation experiments demonstrate the efficiency of atlas guidance and the attention mechanism. The proposed AtlasSeg demonstrated superior segmentation performance against other convolution networks with higher segmentation accuracy, and may facilitate fetal brain MRI analysis in large-scale fetal brain studies.

Automated fetal brain extraction from full-uterus MRI is a challenging task due to variable head sizes, orientations, complex anatomy, and prevalent artifacts. While deep-learning (DL) models trained on synthetic images have been successful in adult brain extraction, adapting these networks for fetal MRI is difficult due to the sparsity of labeled data, leading to increased false-positive predictions. To address this challenge, we propose a test-time strategy that reduces false positives in networks trained on sparse, synthetic labels. The approach uses a breadth-fine search (BFS) to identify a subvolume likely to contain the fetal brain, followed by a deep-focused sliding window (DFS) search to refine the extraction, pooling predictions to minimize false positives. We train models at different window sizes using synthetic images derived from a small number of fetal brain label maps, augmented with random geometric shapes. Each model is trained on diverse head positions and scales, including cases with partial or no brain tissue. Our framework matches state-of-the-art brain extraction methods on clinical HASTE scans of third-trimester fetuses and exceeds them by up to 5\% in terms of Dice in the second trimester as well as EPI scans across both trimesters. Our results demonstrate the utility of a sliding-window approach and combining predictions from several models trained on synthetic images, for improving brain-extraction accuracy by progressively refining regions of interest and minimizing the risk of missing brain mask slices or misidentifying other tissues as brain.

Diffusion-weighted MRI is increasingly used to study the normal and abnormal development of fetal brain in-utero. Recent studies have shown that dMRI can offer invaluable insights into the neurodevelopmental processes in the fetal stage. However, because of the low data quality and rapid brain development, reliable analysis of fetal dMRI data requires dedicated computational methods that are currently unavailable. The lack of automated methods for fast, accurate, and reproducible data analysis has seriously limited our ability to tap the potential of fetal brain dMRI for medical and scientific applications. In this work, we developed and validated a unified computational framework to (1) segment the brain tissue into white matter, cortical/subcortical gray matter, and cerebrospinal fluid, (2) segment 31 distinct white matter tracts, and (3) parcellate the brain's cortex and delineate the deep gray nuclei and white matter structures into 96 anatomically meaningful regions. We utilized a set of manual, semi-automatic, and automatic approaches to annotate 97 fetal brains. Using these labels, we developed and validated a multi-task deep learning method to perform the three computations. Our evaluations show that the new method can accurately carry out all three tasks, achieving a mean Dice similarity coefficient of 0.865 on tissue segmentation, 0.825 on white matter tract segmentation, and 0.819 on parcellation. The proposed method can greatly advance the field of fetal neuroimaging as it can lead to substantial improvements in fetal brain tractography, tract-specific analysis, and structural connectivity assessment.

Diffusion-weighted magnetic resonance imaging (dMRI) is the only non-invasive tool for studying white matter tracts and structural connectivity of the brain. These assessments rely heavily on tractography techniques, which reconstruct virtual streamlines representing white matter fibers. Much effort has been devoted to improving tractography methodology for adult brains, while tractography of the fetal brain has been largely neglected. Fetal tractography faces unique difficulties due to low dMRI signal quality, immature and rapidly developing brain structures, and paucity of reference data. This work presents the first machine learning model for fetal tractography. The model input consists of five sources of information: (1) Fiber orientation, inferred from a diffusion tensor fit to the dMRI signal; (2) Directions of recent propagation steps; (3) Global spatial information, encoded as distances to keypoints in the brain cortex; (4) Tissue segmentation information; and (5) Prior information about the expected local fiber orientations supplied with an atlas. In order to mitigate the local tensor estimation error, a large spatial context around the current point in the diffusion tensor image is encoded using convolutional and attention neural network modules. Moreover, the diffusion tensor information at a hypothetical next point is included in the model input. Filtering rules based on anatomically constrained tractography are applied to prune implausible streamlines. We trained the model on manually-refined whole-brain fetal tractograms and validated the trained model on an independent set of 11 test scans with gestational ages between 23 and 36 weeks. Results show that our proposed method achieves superior performance across all evaluated tracts. The new method can significantly advance the capabilities of dMRI for studying normal and abnormal brain development in utero.

We introduce a conditional implicit neural atlas (CINA) for spatio-temporal atlas generation from Magnetic Resonance Images (MRI) of the neurotypical and pathological fetal brain, that is fully independent of affine or non-rigid registration. During training, CINA learns a general representation of the fetal brain and encodes subject specific information into latent code. After training, CINA can construct a faithful atlas with tissue probability maps of the fetal brain for any gestational age (GA) and anatomical variation covered within the training domain. Thus, CINA is competent to represent both, neurotypical and pathological brains. Furthermore, a trained CINA model can be fit to brain MRI of unseen subjects via test-time optimization of the latent code. CINA can then produce probabilistic tissue maps tailored to a particular subject. We evaluate our method on a total of 198 T2 weighted MRI of normal and abnormal fetal brains from the dHCP and FeTA datasets. We demonstrate CINA's capability to represent a fetal brain atlas that can be flexibly conditioned on GA and on anatomical variations like ventricular volume or degree of cortical folding, making it a suitable tool for modeling both neurotypical and pathological brains. We quantify the fidelity of our atlas by means of tissue segmentation and age prediction and compare it to an established baseline. CINA demonstrates superior accuracy for neurotypical brains and pathological brains with ventriculomegaly. Moreover, CINA scores a mean absolute error of 0.23 weeks in fetal brain age prediction, further confirming an accurate representation of fetal brain development.

Diffusion-weighted Magnetic Resonance Imaging (dMRI) is increasingly used to study the fetal brain in utero. An important computation enabled by dMRI is streamline tractography, which has unique applications such as tract-specific analysis of the brain white matter and structural connectivity assessment. However, due to the low fetal dMRI data quality and the challenging nature of tractography, existing methods tend to produce highly inaccurate results. They generate many false streamlines while failing to reconstruct streamlines that constitute the major white matter tracts. In this paper, we advocate for anatomically constrained tractography based on an accurate segmentation of the fetal brain tissue directly in the dMRI space. We develop a deep learning method to compute the segmentation automatically. Experiments on independent test data show that this method can accurately segment the fetal brain tissue and drastically improve tractography results. It enables the reconstruction of highly curved tracts such as optic radiations. Importantly, our method infers the tissue segmentation and streamline propagation direction from a diffusion tensor fit to the dMRI data, making it applicable to routine fetal dMRI scans. The proposed method can lead to significant improvements in the accuracy and reproducibility of quantitative assessment of the fetal brain with dMRI.

In obstetric ultrasound (US) scanning, the learner's ability to mentally build a three-dimensional (3D) map of the fetus from a two-dimensional (2D) US image represents a significant challenge in skill acquisition. We aim to build a US plane localization system for 3D visualization, training, and guidance without integrating additional sensors. This work builds on top of our previous work, which predicts the six-dimensional (6D) pose of arbitrarily oriented US planes slicing the fetal brain with respect to a normalized reference frame using a convolutional neural network (CNN) regression network. Here, we analyze in detail the assumptions of the normalized fetal brain reference frame and quantify its accuracy with respect to the acquisition of transventricular (TV) standard plane (SP) for fetal biometry. We investigate the impact of registration quality in the training and testing data and its subsequent effect on trained models. Finally, we introduce data augmentations and larger training sets that improve the results of our previous work, achieving median errors of 2.97 mm and 6.63 degrees for translation and rotation, respectively.

The performance of deep neural networks typically increases with the number of training images. However, not all images have the same importance towards improved performance and robustness. In fetal brain MRI, abnormalities exacerbate the variability of the developing brain anatomy compared to non-pathological cases. A small number of abnormal cases, as is typically available in clinical datasets used for training, are unlikely to fairly represent the rich variability of abnormal developing brains. This leads machine learning systems trained by maximizing the average performance to be biased toward non-pathological cases. This problem was recently referred to as hidden stratification. To be suited for clinical use, automatic segmentation methods need to reliably achieve high-quality segmentation outcomes also for pathological cases. In this paper, we show that the state-of-the-art deep learning pipeline nnU-Net has difficulties to generalize to unseen abnormal cases. To mitigate this problem, we propose to train a deep neural network to minimize a percentile of the distribution of per-volume loss over the dataset. We show that this can be achieved by using Distributionally Robust Optimization (DRO). DRO automatically reweights the training samples with lower performance, encouraging nnU-Net to perform more consistently on all cases. We validated our approach using a dataset of 368 fetal brain T2w MRIs, including 124 MRIs of open spina bifida cases and 51 MRIs of cases with other severe abnormalities of brain development.

For many expectant parents, the first opportunity to "meet" their baby comes at 20-weeks of pregnancy. The ultrasound scan performed at that time gives the parents a sense of the health of the growing fetus. The images produced in this important exam reveal the shape and structure of the head and brain, which are of particular interest because severe brain problems may become visible at this stage in the pregnancy. As the brain develops, maternal-fetal specialists keep a close eye on the cerebellum – the part of the brain that coordinates and regulates muscular activity. A healthy cerebellum can typically rule out fetal complications, such as spina bifida – a neural tube defect in which the spinal cord fails to properly develop.