Harmonization mitigates diffusion MRI scanner effects in infancy: insights from the HEALthy Brain and Childhood Development (HBCD) study

The HEALthy Brain and Childhood Development (HBCD) Study is an ongoing longitudinal initiative to understand population-level brain maturation; however, large-scale studies must overcome site-related variance and preserve biologically relevant signal. In addition to diffusion-weighted magnetic resonance imaging images, the HBCD dataset offers analysis-ready derivatives for scientists to conduct their analysis, including scalar diffusion tensor (DTI) metrics in a predetermined set of bundles. The purpose of this study is to characterize HBCD-specific site effects in diffusion MRI data, which have not been systematically reported. In this work, we investigate the sensitivity of HBCD bundle metrics to scanner model-related variance and address these variations with ComBat-GAM harmonization within the current HBCD data release 1.1 across six scanner models. Following ComBat-GAM, we observe zero statistically significant differences between the distributions from any scanner model following FDR correction and reduce Cohen's f effect sizes across all metrics. Our work underscores the importance of rigorous harmonization efforts in large-scale studies, and we encourage future investigations of HBCD data to control for these effects.

Personalized White Matter Bundle Segmentation for Early Childhood

White matter segmentation methods from diffusion magnetic resonance imaging range from streamline clustering-based approaches to bundle mask delineation, but none have proposed a pediatric-specific approach. We hypothesize that a deep learning model with a similar approach to TractSeg will improve similarity between an algorithm-generated mask and an expert-labeled ground truth. Given a cohort of 56 manually labelled white matter bundles, we take inspiration from TractSeg's 2D UNet architecture, and we modify inputs to match bundle definitions as determined by pediatric experts, evaluation to use k fold cross validation, the loss function to masked Dice loss. We evaluate Dice score, volume overlap, and volume overreach of 16 major regions of interest compared to the expert labeled dataset. To test whether our approach offers statistically significant improvements over TractSeg, we compare Dice voxels, volume overlap, and adjacency voxels with a Wilcoxon signed rank test followed by false discovery rate correction. We find statistical significance across all bundles for all metrics with one exception in volume overlap. After we run TractSeg and our model, we combine their output masks into a 60 label atlas to evaluate if TractSeg and our model combined can generate a robust, individualized atlas, and observe smoothed, continuous masks in cases that TractSeg did not produce an anatomically plausible output. With the improvement of white matter pathway segmentation masks, we can further understand neurodevelopment on a population level scale, and we can produce reliable estimates of individualized anatomy in pediatric white matter diseases and disorders.

Fully Differentiable dMRI Streamline Propagation in PyTorch

Diffusion MRI (dMRI) provides a distinctive means to probe the microstructural architecture of living tissue, facilitating applications such as brain connectivity analysis, modeling across multiple conditions, and the estimation of macrostructural features. Tractography, which emerged in the final years of the 20th century and accelerated in the early 21st century, is a technique for visualizing white matter pathways in the brain using dMRI. Most diffusion tractography methods rely on procedural streamline propagators or global energy minimization methods. Although recent advancements in deep learning have enabled tasks that were previously challenging, existing tractography approaches are often non-differentiable, limiting their integration in end-to-end learning frameworks. While progress has been made in representing streamlines in differentiable frameworks, no existing method offers fully differentiable propagation. In this work, we propose a fully differentiable solution that retains numerical fidelity with a leading streamline algorithm. The key is that our PyTorch-engineered streamline propagator has no components that block gradient flow, making it fully differentiable. We show that our method matches standard propagators while remaining differentiable. By translating streamline propagation into a differentiable PyTorch framework, we enable deeper integration of tractography into deep learning workflows, laying the foundation for a new category of macrostructural reasoning that is not only computationally robust but also scientifically rigorous.

DeepFixel: Crossing white matter fiber identification through spherical convolutional neural networks

Diffusion-weighted magnetic resonance imaging allows for reconstruction of models for structural connectivity in the brain, such as fiber orientation distribution functions (ODFs) that describe the distribution, direction, and volume of white matter fiber bundles in a voxel. Crossing white matter fibers in voxels complicate analysis and can lead to errors in downstream tasks like tractography. We introduce one option for separating fiber ODFs by performing a nonlinear optimization to fit ODFs to the given data and penalizing terms that are not symmetric about the axis of the fiber. However, this optimization is non-convex and computationally infeasible across an entire image (approximately 1.01 x 106 ms per voxel). We introduce DeepFixel, a spherical convolutional neural network approximation for this nonlinear optimization. We model the probability distribution of fibers as a spherical mesh with higher angular resolution than a truncated spherical harmonic representation. To validate DeepFixel, we compare to the nonlinear optimization and a fixel-based separation algorithm of two-fiber and three-fiber ODFs. The median angular correlation coefficient is 1 (interquartile range of 0.00) using the nonlinear optimization algorithm, 0.988 (0.317) using a fiber bundle elements or "fixel"-based separation algorithm, and 0.973 (0.004) using DeepFixel. DeepFixel is more computationally efficient than the non-convex optimization (0.32 ms per voxel). DeepFixel's spherical mesh representation is successful at disentangling at smaller angular separations and smaller volume fractions than the fixel-based separation algorithm.