Brain Structure and Function

, Volume 223, Issue 6, pp 2753–2765 | Cite as

Age, sex, and puberty related development of the corpus callosum: a multi-technique diffusion MRI study

  • Sila GencEmail author
  • Charles B. Malpas
  • Gareth Ball
  • Timothy J. SilkEmail author
  • Marc L. Seal
Original Article


The corpus callosum is integral to the central nervous system, and continually develops with age by virtue of increasing axon diameter and ongoing myelination. Magnetic resonance imaging (MRI) techniques offer a means to disentangle these two aspects of white matter development. We investigate the profile of microstructural metrics across the corpus callosum, and assess the impact of age, sex and pubertal development on these processes. This study made use of two independent paediatric populations. Multi-shell diffusion MRI data were analysed to produce a suite of diffusion tensor imaging, neurite orientation dispersion and density imaging, and apparent fibre density (AFD) metrics. A multivariate profile analysis was performed for each diffusion metric across ten subdivisions of the corpus callosum. All diffusion metrics significantly varied across the length of the corpus callosum. AFD exhibited a strong relationship with age across the corpus callosum (partial η2 = 0.65), particularly in the posterior body of the corpus callosum (partial η2 = 0.72). In addition, females had significantly higher AFD compared with males, most markedly in the anterior splenium (partial η2 = 0.14) and posterior genu (partial η2 = 0.13). Age-matched pubertal group differences were localised to the splenium. We present evidence of a strong relationship between apparent fibre density and age, sex, and puberty during development. These results are consistent with ex vivo studies of fibre morphology, providing insights into the dynamics of axonal development in childhood and adolescence using diffusion MRI.


Apparent fibre density White matter Corpus callosum Puberty Development DTI NODDI 



Apparent fibre density


Akaike information criterion


Body mass index


Diffusion tensor imaging


Diffusion-weighted imaging


Confidence interval


Cincinnati MR Imaging of NeuroDevelopment


Constrained spherical deconvolution


Fractional anisotropy


Fixel-based analysis


Fibre orientation distribution


General linear model


Magnetic resonance imaging


Mean diffusivity


Neuroimaging of the Children’s Attention Project


Neurite orientation dispersion and density imaging


Orientation dispersion index


Pubertal development scale




Repetition time


Intra-cellular volume fraction



Data used in the preparation of this article were obtained from the CMIND Data Repository (Contract #s HHSN275200900018C) and NICAP study (National Health and Medical Research Council; project Grant #1065895). This research and analysis was conducted within the Developmental Imaging research group, Murdoch Children’s Research Institute, supported by The Royal Children’s Hospital Foundation and the Victorian Government’s Operational Infrastructure Support Program.

Compliance with ethical standards

Conflict of interest

All authors disclose no real or potential conflicts of interest.

Studies involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Written informed consent was obtained from the parent/guardian of all children in this study. Additionally, informed consent was obtained for adolescents that were aged 18.

Supplementary material

429_2018_1658_MOESM1_ESM.docx (168 kb)
Supplementary material 1 (DOCX 167 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Paediatrics, Melbourne Medical SchoolThe University of MelbourneParkvilleAustralia
  2. 2.Developmental ImagingMurdoch Children’s Research InstituteParkvilleAustralia
  3. 3.Department of Medical Education, Melbourne Medical SchoolThe University of MelbourneParkvilleAustralia
  4. 4.School of PsychologyDeakin UniversityMelbourneAustralia

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