Article Figures & Data
Figures
- Figure 1.
Age at scans for all subjects. Each of the 221 scans obtained is represented by a circle; each of the 103 subjects is shown in a different row, with their scans connected by a straight line. Females (red) and males (blue) are marked separately. Note the relatively even spacing of subjects across the age range, with most subjects receiving two scans ∼4 years apart. Several subjects received three or four scans in total.
- Figure 2.
Longitudinal volume changes on T1-weighted images. Changes of white matter, gray matter, and total brain volume with age for each scan are shown (top row) along with bar graphs reflecting the percentage of subjects with volume increases (green), decreases (red), or no change (blue) within six age categories. White matter volume increased significantly across the age range, including the twenties, while gray matter volume decreased in the majority of children, adolescents, and young adults up to 25 years. These white matter increases and gray matter decreases offset one another such that total brain volume did not change in most persons, although many of the younger subjects had small increases.
- Figure 3.
Longitudinal age-related changes of fractional anisotropy. Individual FA data from 221 scans and bar graphs depicting the percentage of 103 subjects whose FA increased (green), decreased (red), or did not change (blue) in six age groupings are shown for all 10 white matter fibers. All fibers showed significant nonlinear increases of FA with age. In callosal and projection fibers, children and young adolescents had FA increases, while most young adults showed no change of FA (although 30% had increased FA of the body and splenium in 22–32 year group). The majority of young subjects also had FA increases in association fibers, yet importantly these fibers, such as the superior and inferior fronto-occipital, inferior longitudinal, and cingulum, continue to have 30–50% of subjects with FA increases between scans even in the 19–25 and 22–32 year age groups. Tracts displayed are from a 22-year-old male.
- Figure 4.
Longitudinal age-related changes of mean diffusivity. All 10 tracts had significant age-related decreases of MD. Commissural tracts demonstrated expected patterns, where a large proportion of subjects had decreasing MD in childhood and there were fewer subjects with decreases at older ages. Most association tracts, however, demonstrated more prolonged MD decreases, with 30–40% of older subjects having decreases of MD between scans. Notably, the inferior fronto-occipital, inferior longitudinal, and uncinate fasciculi show 40–60% of subjects with increasing MD between scans as early as the 11–19 year group. Other frontal lobe connecting white matter fibers, such as the genu of the corpus callosum and the cingulum, demonstrate 30–40% of subjects with increasing MD but only in the oldest age grouping of 22–32 years suggesting age-related decline is beginning in some subjects.
- Figure 5.
Sample tracts at two time points. Tracts are shown at two time points for several individuals. The superior longitudinal fasciculus (orange), corticospinal tract (green), and inferior longitudinal fasciculus (purple) are given as examples because they can be some of the more difficult and inconsistent fibers to track. Note that, although there are considerable variations in length, size, and shape of the tracts among individuals, the tracts look relatively similar within the same individual.
- Figure 6.
Longitudinal changes of parallel and perpendicular diffusivity. For all tracts, most young subjects had decreased perpendicular diffusivity between scans and fewer older subjects had decreases. Parallel diffusivity trajectories varied more among tracts. Most association fibers (such as the cingulum shown above) had only small changes of parallel diffusivity, although for tracts with prolonged FA changes (superior and inferior longitudinal, shown above, and inferior fronto-occipital fasciculi), a substantial portion of older subjects demonstrated increased parallel diffusivity between scans. Commissural fibers had substantial decreases of both parallel and perpendicular diffusivity in young subjects, with most subjects having no change at older ages. The corticospinal tract was unique in that its parallel diffusivity trajectory increased at young ages; its perpendicular diffusivity trajectory was similar to that of other tracts.
- Figure 7.
Longitudinal changes of tract volume. Volume changes were significant for most tracts, although not for the superior fronto-occipital fasciculus (no trend line shown). Most tracts had linear volume increases across the age range, although the cingulum, genu of the corpus callosum, and the inferior longitudinal fasciculus had quadratic trends with increases then decreases, and the splenium of the corpus callosum showed linear decreases of volume. Note that within-subject increases of tract volumes were observed in 40–50% of subjects in the 19–25 and 22–32 year age groups for the body of the corpus callosum, cingulum, and inferior longitudinal fasciculus.
- Figure 8.
Tract volume relationship with FA and MD changes. The percentage of subjects that showed increases (green), decreases (red), or no change (blue) in tract volume between scans are shown for each group depending on the evolution of FA or MD. While there is a decent proportion of subjects with elevated FA or reduced MD that have increased tract volume, there is a greater proportion of subjects with no change or even a decrease in tract volume in these cases. There is no clear association between tract volume and diffusion parameter changes.
Tables
Tract FA MD (×10−3 mm2/s) λ// (×10−3 mm2/s) λ⊥ (×10−3 mm2/s) Volume (cm3) Genu of the corpus callosum 0.012 0.017 0.023 0.016 1.15 Body of the corpus callosum 0.013 0.022 0.034 0.020 2.29 Splenium of the corpus callosum 0.012 0.024 0.032 0.022 1.06 Corticospinal tract 0.019 0.025 0.030 0.025 1.23 Cingulum 0.016 0.012 0.020 0.017 0.54 Inferior longitudinal fasciculus 0.007 0.012 0.017 0.012 1.27 Inferior fronto-occipital fasciculus 0.012 0.012 0.022 0.011 2.65 Superior longitudinal fasciculus 0.009 0.010 0.012 0.012 1.25 Superior fronto-occipital fasciculus 0.009 0.011 0.013 0.012 0.72 Uncinate fasciculus 0.010 0.012 0.025 0.022 0.83 Seven subjects were scanned three to four times each within 6 months to determine reliability of the diffusion and tract volume measurements over time. The mean of the SDs over all scans per subject are shown for each parameter [FA, MD, parallel (λ//) and perpendicular diffusivity (λ⊥), and tract volume], which were then used as a threshold for determining whether the parameters increased or decreased between scans in the study population.
- Table 2.
Fitting parameters and p values for age-related changes of FA and MD for all 10 white matter fibers
Fractional anisotropy Mean diffusivity (mm2/s) Intercept Age (×10−2) Age2 (×10−3) Sexa Intercept (×10−3) Age (×10−5) Age2 (×10−6) Sex (×10−5)a Commissural tracts Genu of corpus callosum 0.52 <0.001 0.51 <0.001 −0.13 <0.001 n.s. 0.88 <0.001 −0.87 <0.001 0.18 <0.001
0.16 0.004n.s. Body of corpus callosum 0.48 <0.001 0.60 <0.001 −0.14 <0.001 n.s. 0.97 <0.001 −0.97 <0.001 n.s. Splenium of corpus callosum 0.53 <0.001 0.52 0.001 −0.11 0.013 0.013 0.001 0.93 <0.001 −1.36 <0.001 0.31 <0.001 n.s. Projection tracts Corticospinal tractsb 0.86 <0.001 −0.20 <0.001 n.s. 1.2 0.007 Left CSTb 0.43 <0.001 1.03 <0.001 −0.24 <0.001 −0.009 0.004 Right CSTb 0.46 <0.001 0.60 <0.001 −0.13 <0.001 −0.011 0.001 Association tracts Cingulum 0.43 <0.001 0.54 <0.001 −0.07 0.038 −0.014 <0.001 0.88 <0.001 −0.94 <0.001 0.17 <0.001 0.89 0.021 Inferior longitudinal fasciculus 0.41 <0.001 0.47 <0.001 −0.01 0.001 n.s. 0.93 <0.001 −0.79 <0.001 0.16 <0.001 n.s. Inferior fronto-occipital fasciculus 0.45 <0.001 0.68 <0.001 −0.13 <0.001 n.s. 0.88 <0.001 −0.68 <0.001 0.15 <0.001 n.s. Superior longitudinal fasciculus 0.42 <0.001 0.67 <0.001 −0.14 <0.001 −0.005 0.027 0.85 <0.001 −0.89 <0.001 0.17 <0.001 n.s. Superior fronto-occipital fasciculus 0.41 <0.001 0.53 <0.001 −0.13 <0.001 n.s. 0.82 <0.001 −0.62 <0.001 0.11 0.002 0.81 0.017 Uncinate fasciculus 0.37 <0.001 0.44 <0.001 −0.08 0.011 −0.009 0.002 0.90 <0.001 −0.58 <0.001 0.10 <0.001 n.s. CST, Corticospinal tract; n.s., not significant.
↵aPositive values for sex term indicate higher FA or MD values in females.
↵bThe CST was assessed separately for each hemisphere for FA measures, where there were significant differences in the age and age2 parameters; for MD, there were no significant differences, so hemispheres were combined.
