McMaster, Elyssa M.; Newlin, Nancy R.; Cho, Chloe; Rudravaram, Gaurav; Saunders, Adam M.; Krishnan, Aravind R.; Remedios, Lucas W.; Kim, Michael E.; Xu, Hanliang; Schilling, Kurt G.; Rheault, François; Cutting, Laurie E.; Landman, Bennett Allan. (2025). Sensitivity of quantitative diffusion MRI tractography and microstructure to anisotropic spatial sampling. Magnetic Resonance Imaging, 124, 110539. https://doi.org/10.1016/j.mri.2025.110539
Diffusion-weighted MRI (dMRI) is a powerful brain imaging technique that helps scientists study how nerve fibers, or white matter, are organized and connected in the brain. This method allows researchers to map the brain’s “connectome”—a network-like model that shows how different regions communicate. However, the accuracy of these maps can be affected by the shape and size of the 3D pixels, called voxels, used in the scans. When voxels are not perfect cubes (a condition called anisotropy), they can distort measurements of brain structure, but the full extent of this effect hasn’t been well understood.
In this study, we explored how anisotropic voxels influence both the fine details of brain tissue (microstructural measures like fractional anisotropy and mean diffusivity) and larger white matter features (such as bundle volume, length, and surface area). We analyzed brain scans from 44 participants in the Human Connectome Project, comparing data collected at different voxel resolutions. Using statistical tests, we examined how changing voxel shape affected key measurements of white matter structure and connectivity.
Our findings showed that even small changes in voxel shape caused significant differences in at least one microstructural and one bundle-related measure at every tested resolution. This means that voxel anisotropy can meaningfully alter how we interpret brain microstructure and tractography results. We also found that while certain detailed tissue measures could not be accurately restored through simple image upsampling, the consistency of larger white matter bundle measurements improved when data were resampled to 1 mm isotropic voxels.
In short, this study highlights how subtle differences in imaging resolution can affect the accuracy and reliability of brain connectivity studies, emphasizing the need for careful voxel selection and correction methods in diffusion MRI research.
Fig. 1. We illustrate the range of voxels used for this experiment with tensor and tractogram representation. We see a bias in the tensor model toward the superior-inferior direction in the anisotropic voxels when compared to the isotropic sampling. The tractogram’s representation of the corpus callosum dramatically changes based on spatial sampling; the highly anisotropic voxels influence the tracking behavior to generate superior-inferior streamlines when the corpus callosum’s anatomy includes right-left whtie matter.