Disentangling crossing fibers with advanced dMRI methods reveals bundle-specific degeneration across the visual system in asymmetric glaucoma.

Overview

1. Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico. Blvd. Juriquilla, Queretaro, Queretaro, Mexico
2. Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, New York, United States of America
3. Centro de Investigación en Matemáticas A.C., Guanajuato, México
4. Sherbrooke Connectivity Imaging Lab (SCIL), Computer Science, Université de Sherbrooke, Sherbrooke, Quebec, Canada
5. Instituto Mexicano de Oftalmologia IAP, Querétaro, Mexico

Abstract

Diffusion magnetic resonance imaging (dMRI) is a non-invasive neuroimaging technique that enables in vivo assessment of white matter microstructure and is highly sensitive to tissue alterations associated with disease. Although substantial evidence links diffusion-derived metrics to underlying white matter tissue properties, the presence of complex within-voxel axonal configurations complicates their biological interpretation. Several methods have been proposed to assess diffusion properties of individual crossing axonal populations, but their validation and clinical applicability remain limited. Glaucoma, the second leading cause of blindness worldwide, is characterized by progressive loss of retinal ganglion cells and axonal damage in the optic nerve, leading to degeneration along the entire visual pathway. This degeneration includes secondary effects on fiber crossings within the optic chiasm, which are challenging to characterize with conventional diffusion methods. Here, we evaluated whether advanced diffusion metrics can detect microstructural alterations in these complex white matter configurations and whether these measures correlate with clinical markers of glaucoma severity. In this study, we evaluated 31 patients with asymmetric glaucoma and 31 healthy controls using advanced diffusion magnetic resonance imaging methods, including Diffusion Tensor Imaging, Constrained Spherical Deconvolution, multi-tensor fit via Multi-Resolution Discrete Search method, and Fixel-Based Analysis. We found significant differences of diffusion metrics in white matter tracts of the visual system, including the optic nerve, optic chiasm, optic tracts, and optic radiations. Moreover, diffusion metrics correlated with clinical ophthalmological parameters such as cup-to-disc ratio, visual field mean deviation, and retinal nerve fiber layer thickness. These findings support the use of advanced diffusion magnetic resonance imaging models as sensitive tools for detecting Wallerian degeneration and resolving complex white matter architecture in the human visual pathway, and demonstrate their utility to study other fiber-crossing regions throughout the brain.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• openneuro:ds006837, at OpenNeuro; found in “Data Availability”

Data Availability

All anonymized images and patient information are available in BIDS format at https://openneuro.org/datasets/ds006837.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 13 MeSH terms, 2 funders, 61 references.

Cite

This paper

Coutiño, D., Guerrero-Zavala, J., Domínguez-Frausto, C. A., García-Guillén, M., Coronado-Leija, R., Ramírez-Manzanares, A., Hernández-Gutiérrez, E., Descoteaux, M., Ayala, M., Badillo, M., & Concha, L. (2026). Disentangling crossing fibers with advanced dMRI methods reveals bundle-specific degeneration across the visual system in asymmetric glaucoma. PloS one, 21(6), e0349951. https://doi.org/10.1371/journal.pone.0349951

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