Schilling, Kurt G., Newton, Allen, Tax, Chantal, Nilsson, Markus, Chamberland, Maxime, Anderson, Adam, Landman, Bennett, & Descoteaux, Maxime. (2025). White matter geometry confounds diffusion tensor imaging along perivascular space (DTI-ALPS) measures. *Human Brain Mapping, 46*(10), e70282. https://doi.org/10.1002/hbm.70282
The perivascular space (PVS) plays an important role in helping the brain clear out waste by allowing fluid to flow around blood vessels. A brain imaging method called DTI-ALPS was suggested as a way to measure how fluid moves in these spaces without surgery. However, it’s not clear how accurate or specific this method is. The DTI-ALPS method assumes certain patterns in brain tissue called “radial symmetrby” and interprets when these patterns are uneven (called “radial asymmetry”) as a sign of fluid movement in the PVS. But other factors in the brain’s structure might affect these measurements.
In this study, we carefully examined these possible influences using detailed brain scans from the Human Connectome Project and high-resolution imaging. We looked at how common radial asymmetry is in brain white matter, how crossing nerve fibers affect the measurements, how nerve fibers’ twisting and spreading impact results, and how blood vessels are oriented in these brain areas. We found that radial asymmetry happens widely in white matter and is mostly caused by the shape and arrangement of nerve fibers—not just fluid in the PVS. Crossing fibers made the measurements seem larger, and twisting or spreading of fibers also caused asymmetry, regardless of fluid flow. Additionally, blood vessels were not always aligned in the way the method assumes.
Overall, the DTI-ALPS measurements are strongly influenced by the brain’s nerve fiber structure rather than just fluid movement in the perivascular space. This means that using DTI-ALPS as a direct marker of the brain’s waste clearance system might be misleading unless these structural factors are considered. Future research should use more advanced methods to separate the effects of fluid flow from the complex structure of brain tissue.
Fig 1
Radial asymmetry is widespread throughout white matter. Sagittal, coronal, and axial slices of an example HCP subject show radial asymmetry at all diffusion weightings, and throughout white matter, with most regions exhibiting average asymmetry values ~1.3–1.8, with many voxels > 2.
