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. To address these challenges, this work presents a machine learning model, based on a deep neural network, for fetal tractography. The model input consists of five different sources of information: (1) Voxel-wise fiber orientation, inferred from a diffusion tensor fit to the dMRI signal; (2) Directions of recent propagation steps; (3) Global spatial information, encoded as normalized 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 subjects with gestational ages between 23 and 36 weeks. Results show that our proposed method achieves superior performance across all evaluated tracts. Qualitative assessments on independent data from the Developing Human Connectome Project demonstrated the generalizability of our method. The new method can significantly advance the capabilities of dMRI for studying normal and abnormal brain development in utero.

Diffusion magnetic resonance imaging (dMRI) is pivotal for probing the microstructure of the rapidly-developing fetal brain. However, fetal motion during scans and its interaction with magnetic field inhomogeneities result in artifacts and data scattering across spatial and angular domains. The effects of those artifacts are more pronounced in high-angular resolution fetal dMRI, where signal-to-noise ratio is very low. Those effects lead to biased estimates and compromise the consistency and reliability of dMRI analysis. This work presents High Angular resolution diffusion Imaging reconsTruction and Correction approacH (HAITCH), the first and the only publicly available tool to correct and reconstruct multi-shell high-angular resolution fetal dMRI data. HAITCH offers several technical advances that include a blip-reversed dual-echo acquisition for dynamic distortion correction, advanced motion correction for model-free and robust reconstruction, optimized multi-shell design for enhanced information capture and increased tolerance to motion, and outlier detection for improved reconstruction fidelity. The framework is open-source, flexible, and can be used to process any type of fetal dMRI data, including single-echo or single-shell acquisitions, but is most effective when used with multi-shell multi-echo fetal dMRI data that cannot be processed with any of the existing tools. Validation experiments on real fetal dMRI scans demonstrate significant improvements and accurate correction across diverse fetal ages and motion levels. HAITCH successfully removes artifacts and reconstructs high-fidelity fetal dMRI data suitable for advanced diffusion modeling, including fiber orientation distribution function estimation. These advancements pave the way for more reliable analysis of the fetal brain microstructure and tractography under challenging imaging conditions.

Diffusion-weighted magnetic resonance imaging (dMRI) of the brain offers unique capabilities including noninvasive probing of tissue microstructure and structural connectivity. It is widely used for clinical assessment of disease and injury, and for neuroscience research. Analyzing the dMRI data to extract useful information for medical and scientific purposes can be challenging. The dMRI measurements may suffer from strong noise and artifacts, and may exhibit high intersession and interscanner variability in the data, as well as intersubject heterogeneity in brain structure. Moreover, the relationship between measurements and the phenomena of interest can be highly complex. Recent years have witnessed increasing use of machine learning methods for dMRI analysis. This manuscript aims to assess these efforts, with a focus on methods that have addressed data preprocessing and harmonization, microstructure mapping, tractography, and white matter tract analysis. We study the main findings, strengths, and weaknesses of the existing methods and suggest topics for future research. We find that machine learning may be exceptionally suited to tackle some of the difficult tasks in dMRI analysis. However, for this to happen, several shortcomings of existing methods and critical unresolved issues need to be addressed. There is a pressing need to improve evaluation practices, to increase the availability of rich training datasets and validation benchmarks, as well as model generalizability, reliability, and explainability concerns.