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Updated: Mar 26, 2026

Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging
Published on: November 8, 2012
In vivo observation and biophysical interpretation of time-dependent diffusion in human white matter
Els Fieremans1, Lauren M Burcaw1, Hong-Hsi Lee1
1Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY 10016, USA.
Abstract:
The presence of micrometer-level restrictions leads to a decrease of diffusion coefficient with diffusion time. Here we investigate this effect in human white matter in vivo. We focus on a broad range of diffusion times, up to 600 ms, covering diffusion length scales up to about 30 μm. We perform stimulated echo diffusion tensor imaging on 5 healthy volunteers and observe a relatively weak time-dependence in diffusion transverse to major fiber tracts. Remarkably, we also find notable time-dependence in the longitudinal direction. Comparing models of diffusion in ordered, confined and disordered media, we argue that the time-dependence in both directions can arise due to structural disorder, such as axonal beads in the longitudinal direction, and the random packing geometry of fibers within a bundle in the transverse direction. These time-dependent effects extend beyond a simple picture of Gaussian compartments, and may lead to novel markers that are specific to neuronal fiber geometry at the micrometer scale.
Insights
Diffusion MRI reveals time-dependent diffusion in human white matter. Structural complexity, like axonal beads and fiber packing, influences diffusion across different time scales, offering new insights into neuronal geometry.
Area of Science:
- Neuroimaging
- Biophysics
- Diffusion MRI
Background:
- Micrometer-level restrictions in biological tissues affect diffusion.
- Understanding diffusion time-dependence is crucial for interpreting diffusion MRI data.
Purpose of the Study:
- Investigate the effect of diffusion time on diffusion coefficients in human white matter in vivo.
- Explore diffusion time-dependence across a range of diffusion times (up to 600 ms) and length scales (up to 30 μm).
Main Methods:
- Stimulated echo diffusion tensor imaging (DTI) was performed on 5 healthy volunteers.
- Analysis focused on diffusion time-dependence in longitudinal and transverse directions relative to major fiber tracts.
Main Results:
- Observed weak time-dependence in diffusion transverse to major fiber tracts.
- Found notable time-dependence in the longitudinal diffusion direction.
- Time-dependence was observed across diffusion lengths up to approximately 30 μm.
Conclusions:
- Structural disorder, including axonal beading and fiber packing geometry, contributes to diffusion time-dependence.
- Time-dependent diffusion effects extend beyond simple Gaussian compartment models.
- These findings may lead to novel diffusion MRI markers specific to neuronal fiber geometry at the micrometer scale.
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