Fractional anisotropy of water diffusion in cerebral white matter across the lifespan

Abstract

Determining the time of peak of cerebral maturation is vital for our understanding of when cerebral maturation ceases and the cerebral degeneration in healthy aging begins. We carefully mapped changes in fractional anisotropy (FA) of water diffusion for eleven major cerebral white matter tracts in a large group (831) of healthy human subjects aged 11-90. FA is a neuroimaging index of micro-structural white matter integrity, sensitive to age-related changes in cerebral myelin levels, measured using diffusion tensor imaging. The average FA values of cerebral white matter (WM) reached peak at the age 32 ± 6 years. FA measurements for all but one major cortical white matter tract (cortico-spinal) reached peaks between 23 and 39 years of age. The maturation rates, prior to age-of-peak were significantly correlated (r=0.74; p=0.01) with the rates of decline, past age-of-peak. Regional analysis of corpus callosum (CC) showed that thinly-myelinated, densely packed fibers in the genu, that connect pre-frontal areas, maturated later and showed higher decline in aging than the more thickly myelinated motor and sensory areas in the body and splenium of CC. Our findings can be summarized as: associative, cerebral WM tracts that reach their peak FA values later in life also show progressively higher age-related decline than earlier maturing motor and sensory tracts. These findings carry multiple and diverse implications for both theoretical studies of the neurobiology of maturation and aging and for the clinical studies of neuropsychiatric disorders.

Figure 1

Skeletonized, average FA values are shown on the population average FA image. WM-tract labels for eleven major tract are taken from John-Hopkins DTI WM atlas. The average FA values were calculated for the following tracts: CR(corona radiata), SLF (superior longitudinal fasciculus), Cingulate, EC (external capsule), IC (internal capsule), FO (fronto-occipital), CST (cortico-spinal), SS (sagittal striatum) and the Genu, Body and Splenium of Corpus Callosum

Figure 2

Average FA values (●) stratified in 5 year intervals and age-related quadratic (solid curve, FA=0.52 + 22·10−4*age – 0.30 ·10−4*age2, r=0.49, p<1 ·10–24) and linear maturation (dashed line, FA=0.51+14.1·10−4*age, r=0.33, p=10−8) and decline (dotted line, FA=0.59–14.3·10−4*age, r=0.57, p=·10–16) trends for average FA. Age-of-peak (AOP) = 32.1±5.9 years.

Figure 3

FA values for Corona Radiata (■) and Cortical-Spinal tract (Δ) stratified in 5-year intervals. Age-related quadratic (thin curve, FA=0.46+15.6·10−4*age–0.27·10−4*age2, r=0.58, p<1 ·10–24) and linear maturation (dashed line, FA=0.46+4.6·10−4*age, r=0.1, p=0.8) and decline (dotted line, FA=0.51–13.3·10−4*age, r=0.64, p<10–16) trends are shown for Corona Radiata (age-of-peak (AOP)=27.9±5.7years). Quadratic (thin curve, FA=0.45+1.3·10−4*age–0.01 ·10−4*age2, r=0.17, p=0.03) trend is also shown for the Cortical-Spinal tract where the model was not significant and age-of-peak could not be calculated

Figure 4

By-tract FA rate of decline versus by- tract FA rate of maturation