Microstructural maturation of the human brain from childhood to adulthood C. Lebel, a,1 L. Walker, a,1 A. Leemans, b,c L. Phillips, d and C. Beaulieu a, ⁎ a Department of Biomedical Engineering, Faculty of Medicine and Dentistry, Room 1098 Research Transition Facility, University of Alberta, Edmonton, Alberta, Canada T6G 2V2 b School of Psychology (CUBRIC), Cardiff University, Cardiff, UK c Department of Physics (Visionlab), Antwerp University, Antwerp, Belgium d Canadian Centre for Research on Literacy, University of Alberta, Edmonton, Alberta, Canada Received 8 May 2007; revised 14 September 2007; accepted 23 December 2007 Available online 11 January 2008 Brain maturation is a complex process that continues well beyond infancy, and adolescence is thought to be a key period of brain rewiring. To assess structural brain maturation from childhood to adulthood, we charted brain development in subjects aged 5 to 30 years using diffusion tensor magnetic resonance imaging, a novel brain imaging technique that is sensitive to axonal packing and myelination and is particularly adept at virtually extracting white matter connections. Age-related changes were seen in major white matter tracts, deep gray matter, and subcortical white matter, in our large (n = 202), age-distributed sample. These diffusion changes followed an exponential pattern of maturation with considerable regional variation. Differences observed in develop- mental timing suggest a pattern of maturation in which areas with fronto-temporal connections develop more slowly than other regions. These in vivo results expand upon previous postmortem and imaging studies and provide quantitative measures indicative of the progression and magnitude of regional human brain maturation. © 2007 Elsevier Inc. All rights reserved. Introduction Brain development is a complex process linked with behavioral, emotional, cognitive, and overall maturation that progresses throughout childhood, adolescence, and into adulthood. A thorough knowledge of structural brain development during adolescence is crucial for understanding the extensive cognitive and behavioral advances that occur during the same period, and for linking brain structure with brain function in both healthy and disease states. Postmortem studies can and have provided valuable insight into white matter development, demonstrating continued myelination of white matter tracts into the second and third decades of life (Yakovlev and Lecours, 1967; Benes, 1989). However, these studies are limited by the availability of young, previously healthy subjects. Magnetic resonance imaging (MRI) is a powerful tool that has made it possible to investigate healthy brain development in vivo, demonstrating both global brain development, as well as more spe- cific brain maturation. MRI has been used extensively to study brain and tissue volume changes, and has demonstrated that though total brain volume remains approximately constant after early childhood, the volume of the individual tissue components changes throughout the life span (Giedd et al., 1999; Good et al., 2001). Studies of cortical gray matter development have shown regional patterns of brain maturation, with distinct areas developing at different rates (Sowell et al., 2004; Lerch et al., 2006; Whitford et al., 2007). Despite the fact that adolescence is considered a crucial period of brain rewiring, relatively little is known about the development of the white matter tracts that form this wiring or the deep gray matter structures that provide the relay stations. Previous studies using T1- weighted anatomical MRI have shown various brain white matter changes during adolescence, including an overall volume increase (Giedd et al., 1999), and increases of “white matter density” in the internal capsule and the left arcuate fasciculus (Paus et al., 1999). Diffusion tensor MRI (DTI) is a non-invasive tool that provides unique information about tissue microstructure, including indirect measures of myelination and axonal growth, and may be more sen- sitive than conventional imaging (Basser et al., 1994; Beaulieu, 2002; Le Bihan, 2003). DTI has demonstrated more widespread white matter and deep gray matter development with age during childhood and adolescence (Mukherjee et al., 2001; Schmithorst et al., 2002; Barnea-Goraly et al., 2005; Ben Bashat et al., 2005; Snook et al., 2005; Ashtari et al., 2007) than is observed on T1- weighted scans. However, previous DTI studies of adolescence were limited by small sample sizes (Morriss et al., 1999; Eluvathingal et al., 2007), limited brain regions analyzed (Ben Bashat et al., 2005; www.elsevier.com/locate/ynimg NeuroImage 40 (2008) 1044 – 1055 ⁎ Corresponding author. Fax: +1 780 492 8259. E-mail address: christian.beaulieu@ualberta.ca (C. Beaulieu). 1 These authors contributed equally to this work. Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2007.12.053