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Neuroimage. 2016 Mar;128:180-192. doi: 10.1016/j.neuroimage.2015.12.033. Epub 2015 Dec 24.

Age effects and sex differences in human brain white matter of young to middle-aged adults: A DTI, NODDI, and q-space study.

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Department of Psychological and Brain Sciences and Dartmouth Brain Imaging Center, Dartmouth College, 6207, Moore Hall, Hanover, NH 03755, USA.
Departments of Medical Physics and Psychiatry, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA; Waisman Laboratory for Brain Imaging and Behavior, 1500 Highland Ave, Madison, WI 53705, USA.
Department of Biostatistics, Richard M. Fairbanks School of Public Health and School of Medicine, Indiana University, 410 W 10th St., Suite 3000, Indianapolis, IN 46202, USA.
Department of Psychiatry, Indiana University School of Medicine, Goodman Hall 355 W. 16th St., Suite 4800, Indianapolis, IN 46202, USA.
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Goodman Hall, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202, USA. Electronic address:


Microstructural changes in human brain white matter of young to middle-aged adults were studied using advanced diffusion Magnetic Resonance Imaging (dMRI). Multiple shell diffusion-weighted data were acquired using the Hybrid Diffusion Imaging (HYDI). The HYDI method is extremely versatile and data were analyzed using Diffusion Tensor Imaging (DTI), Neurite Orientation Dispersion and Density Imaging (NODDI), and q-space imaging approaches. Twenty-four females and 23 males between 18 and 55years of age were included in this study. The impact of age and sex on diffusion metrics were tested using least squares linear regressions in 48 white matter regions of interest (ROIs) across the whole brain and adjusted for multiple comparisons across ROIs. In this study, white matter projections to either the hippocampus or the cerebral cortices were the brain regions most sensitive to aging. Specifically, in this young to middle-aged cohort, aging effects were associated with more dispersion of white matter fibers while the tissue restriction and intra-axonal volume fraction remained relatively stable. The fiber dispersion index of NODDI exhibited the most pronounced sensitivity to aging. In addition, changes of the DTI indices in this aging cohort were correlated mostly with the fiber dispersion index rather than the intracellular volume fraction of NODDI or the q-space measurements. While men and women did not differ in the aging rate, men tend to have higher intra-axonal volume fraction than women. This study demonstrates that advanced dMRI using a HYDI acquisition and compartmental modeling of NODDI can elucidate microstructural alterations that are sensitive to age and sex. Finally, this study provides insight into the relationships between DTI diffusion metrics and advanced diffusion metrics of NODDI model and q-space imaging.


Aging; Axonal density; Diffusion tensor; Fractional anisotropy; Intra-cellular volume fraction; NODDI; Orientation dispersion index; Sex; White matter

[Available on 2017-03-01]
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