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Diffusion MRI Microstructure Markers of Changes in the Human Brain Across the Lifespan Using Constrained Spherical
Benjamin T Newman1,2, John D Van Horn2,3, T Jason Druzgal1
1Department of Radiology and Medical Imaging, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
Human Brain Mapping
|November 14, 2025
Summary
This study reveals how brain microstructure changes with age using advanced MRI techniques. It maps these changes across the lifespan in healthy individuals, providing a baseline for future research.
Area of Science:
- Neuroscience
- Brain Development
- Aging Research
Background:
- Understanding brain development, maturation, aging, and decline is crucial in neuroscience.
- Diffusion MRI metrics offer insights into brain microstructure.
- Lifespan studies are essential for characterizing normative brain changes.
Purpose of the Study:
- To investigate the relationship between brain diffusion microstructure and chronological age.
- To utilize 3-tissue constrained spherical deconvolution (3T-CSD) and fixel-based metrics for microstructural analysis.
- To establish normative microstructural trajectories across the lifespan in a healthy cohort.
Main Methods:
- Employed 3-tissue constrained spherical deconvolution (3T-CSD) and fixel-based derivatives.
- Analyzed diffusion MRI data from the Nathanial Kline Institute's Rockland cohort (409 subjects, ages 5-85).
- Quantified microstructural metrics in white matter, subcortical gray matter, and cortical regions, assessing lateral differences.
Main Results:
- Identified age-related trajectories for various microstructural metrics, including extracellular free water, intracellular isotropic, intracellular anisotropic, fiber density and cross-section, g-ratio, and conduction velocity.
- Observed general trends of positive association with age for extracellular signal fraction and g-ratio, negative for intracellular isotropic signal fraction, fiber density/cross-section, and conduction velocity, and an inverted U-shape for intracellular anisotropic signal fraction.
- Found significant structural and lateral differences in microstructure measurements across different brain regions.
Conclusions:
- 3T-CSD and fixel-based metrics effectively describe age-related changes in brain microstructure across the lifespan.
- This study provides a normative reference for analyzing microstructural changes in relation to pathology or behavior.
- Detailed analysis of lateralized results can guide future diffusion microstructure studies of cortical and subcortical regions.
