The development of brain white matter microstructure

Abstract

Throughout infancy, childhood, and adolescence, our brains undergo remarkable changes. Processes including myelination and synaptogenesis occur rapidly across the first 2-3 years of life, and ongoing brain remodeling continues into young adulthood. Studies have sought to characterize the patterns of structural brain development, and early studies predominately relied upon gross anatomical measures of brain structure, morphology, and organization. MRI offers the ability to characterize and quantify a range of microstructural aspects of brain tissue that may be more closely related to fundamental neurodevelopmental processes. Techniques such as diffusion, magnetization transfer, relaxometry, and myelin water imaging provide insight into changing cyto- and myeloarchitecture, neuronal density, and structural connectivity. In this review, we focus on the growing body of literature exploiting these MRI techniques to better understand the microstructural changes that occur in brain white matter during maturation. Our review focuses on studies of normative brain development from birth to early adulthood (∼25 years), and places particular emphasis on longitudinal studies and newer techniques that are being used to study microstructural white matter development. All imaging methods demonstrate consistent, rapid microstructural white matter development over the first 3 years of life, suggesting increased myelination and axonal packing. Diffusion studies clearly demonstrate continued white matter maturation during later childhood and adolescence, though the lack of consistent findings in other modalities suggests changes may be mainly due to axonal packing. An emerging literature details differential microstructural development in boys and girls, and connects developmental trajectories to cognitive abilities, behaviour, and/or environmental factors, though the nature of these relationships remains unclear. Future research will need to focus on newer imaging techniques and longitudinal studies to provide more detailed information about microstructural white matter development, particularly in the childhood years.

Keywords: Brain MRI; Brain development; Myelination; Neuroimaging; White matter.

Figure 1

MRI contrast ‘stains’ acquired on the same 11 year-old female, including a conventional T₁-weighted image, and maps of diffusion parameters (FA, RD, and NDI), myelin water fraction (MWF), myelin thickness (g ratio), and pseudo-quantitative inhomogeneous and homogeneous magnetization transfer (qihMT and qMT).

Figure 2

Developmental trends of white matter, gray matter, and total brain volume across childhood, adolescence, and young adulthood. White matter, gray matter, and total brain volume increase markedly across childhood (top row, 0–5 y). White matter volume continues to increase into young adulthood (bottom row, 5–32 years), while gray matter volume decreases and total brain volume remains stable. Data in the bottom row is longitudinal, so multiple scans from the same individual are connected by a line. Top row is unpublished data from Deoni et al.; bottom row data is adapted from Lebel and Beaulieu 2011.

Figure 3

Myelin water fraction (MWF, top row) T1 (middle), and T2 (bottom) change considerably throughout the brain across early childhood, show here from 3–60 months (5 years). A trend is evident with central areas myelinating before peripheral areas. Figure is adapted from Deoni et al., 2012.

Figure 4

Developmental trajectories through infancy and early childhood show rapid changes over the first 2–3 years of life and many appear to plateau by 5 years. Data shown here is taken from several different studies (listed below plots) using a variety of methods to image brain microstructure. Overall, a trend is evident with earlier plateaus in the splenium versus the genu of the corpus callosum, suggesting a posterior-to-anterior pattern of development.

Figure 5

Individual tractography results for the superior longitudinal fasciculus (orange), inferior longitudinal fasciculus (magenta), and corticospinal tracts (green) are shown in three representative healthy individuals at different ages. The whole dataset is shown in scatterplots at right, with data from the individuals shown at left identified in colour. The scatter plots show later maturation in the superior longitudinal fasciculus compared to the other regions. Ages of peak FA values were 21 and 23 years for the left and right corticospinal tracts, and 24 and 25 years for the inferior and superior longitudinal fasciculi, respectively. Figure is adapted from Lebel and Beaulieu 2011.