Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping

Abstract

The elaboration of the myelinated white matter is essential for normal neurodevelopment, establishing and mediating rapid communication pathways throughout the brain. These pathways facilitate the synchronized communication required for higher order behavioral and cognitive functioning. Altered neural messaging (or ‘disconnectivity’) arising from abnormal white matter and myelin development may underlie a number of neurodevelopmental psychiatric disorders. Despite the vital role myelin plays, few imaging studies have specifically examined its maturation throughout early infancy and childhood. Thus, direct investigations of the relationship(s) between evolving behavioral and cognitive functions and the myelination of the supporting neural systems have been sparse. Further, without knowledge of the ‘normative’ developmental time-course, identification of early abnormalities associated with developmental disorders remains challenging. In this work, we examined the use of longitudinal (T ₁) and transverse (T ₂) relaxation time mapping, and myelin water fraction (MWF) imaging to investigate white matter and myelin development in 153 healthy male and female children, 3 months through 60 months in age. Optimized age-specific acquisition protocols were developed using the DESPOT and mcDESPOT imaging techniques; and mean T ₁, T ₂ and MWF trajectories were determined for frontal, temporal, occipital, parietal and cerebellar white matter, and genu, body and splenium of the corpus callosum. MWF results provided a spatio-temporal pattern in-line with prior histological studies of myelination. Comparison of T ₁, T ₂ and MWF measurements demonstrates dissimilar sensitivity to tissue changes associated with neurodevelopment, with each providing differential but complementary information.

Highlights

► Investigate brain T ₁, T ₂ and myelin water fraction development across childhood ► Establish protocols for non-sedated infant and toddler imaging ► Regional T ₁, T ₂ and MWF trajectories spanning the first 5 years of life ► Comparison between, T ₁, T ₂ and MWF estimates across the age range