An Age-Specific Atlas for Delineation of White Matter Pathways in Children Aged 6-8 Years

Diffusion MRI allows non-invasive assessment of white matter maturation in typical development and of white matter damage due to brain injury or pathology. Probabilistic white matter atlases provide delineation of white matter tracts, allowing diffusion metrics to be measured in specific white matter pathways. However, given the known age-dependency of developmental change in white matter it may not be optimal to use an adult template when assessing data acquired from children. This study develops an age-specific probabilistic white matter atlas for delineation of 12 major white matter tracts in children aged 6-8 years. By comparing to subject-specific tract tracing in two validation cohorts, we demonstrate that this age-specific atlas gives better overall performance than simply registering to the Johns Hopkins University adult white matter template. Specifically, when normalising diffusion data acquired from children to an adult template, estimates of fractional anisotropy (FA) values for corticospinal tract, uncinate fasciculus, forceps minor, cingulate gyrus part of the cingulum and anterior thalamic radiation were all less accurate than those obtained when using an age-specific atlas, potentially leading to false negatives when performing group comparisons. We then applied the newly developed atlas to compare FA between children treated with therapeutic hypothermia for neonatal encephalopathy and age-matched controls, which revealed significant reductions in the fornix, the left superior longitudinal fasciculus, and both the hippocampal and cingulum parts of the left cingulate gyrus. To our knowledge, this is the first publicly available probabilistic atlas of white matter tracts for this age group.

Differential White Matter Maturation from Birth to 8 Years of Age

Comprehensive delineation of white matter (WM) microstructural maturation from birth to childhood is critical for understanding spatiotemporally differential circuit formation. Without a relatively large sample of datasets and coverage of critical developmental periods of both infancy and early childhood, differential maturational charts across WM tracts cannot be delineated. With diffusion tensor imaging (DTI) of 118 typically developing (TD) children aged 0–8 years and 31 children with autistic spectrum disorder (ASD) aged 2–7 years, the microstructure of every major WM tract and tract group was measured with DTI metrics to delineate differential WM maturation. The exponential model of microstructural maturation of all WM was identified. The WM developmental curves were separated into fast, intermediate, and slow phases in 0–8 years with distinctive time period of each phase across the tracts. Shorter periods of the fast and intermediate phases in certain tracts, such as the commissural tracts, indicated faster earlier development. With TD WM maturational curves as the reference, higher residual variance of WM microstructure was found in children with ASD. The presented comprehensive and differential charts of TD WM microstructural maturation of all major tracts and tract groups in 0–8 years provide reference standards for biomarker detection of neuropsychiatric disorders.