title: Diffusion kurtosis metrics as biomarkers of microstructural development: A comparative study of a group of children and a group of adults.
abstract: The most common modality of diffusion MRI used in the ageing and development studies is diffusion tensor imaging (DTI) providing two key measures, fractional anisotropy and mean diffusivity. Here, we investigated diffusional changes occurring between childhood (average age 10.3 years) and mitddle adult age (average age 54.3 years) with the help of diffusion kurtosis imaging (DKI), a recent novel extension of DTI that provides additional metrics quantifying non-Gaussianity of water diffusion in brain tissue. We performed voxelwise statistical between-group comparison of diffusion tensor and kurtosis tensor metrics using two methods, namely, the tract-based spatial statistics (TBSS) and the atlas-based regional data analysis. For the latter, fractional anisotropy, mean diffusivity, mean diffusion kurtosis, and other scalar diffusion tensor and kurtosis tensor parameters were evaluated for white matter fibres provided by the Johns-Hopkins-University Atlas in the FSL toolkit (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/Atlases). Within the same age group, all evaluated parameters varied depending on the anatomical region. TBSS analysis showed that changes in kurtosis tensor parameters beyond adolescence are more widespread along the skeleton in comparison to the changes of the diffusion tensor metrics. The regional data analysis demonstrated considerably larger between-group changes of the diffusion kurtosis metrics than of diffusion tensor metrics in all investigated regions. The effect size of the parametric changes between childhood and middle adulthood was quantified using Cohen's d. We used Cohen's d related to mean diffusion kurtosis to examine heterogeneous maturation of various fibres. The largest changes of this parameter (interpreted as reflecting the lowest level of maturation by the age of children group) were observed in the association fibres, cingulum (gyrus) and cingulum (hippocampus) followed by superior longitudinal fasciculus and inferior longitudinal fasciculus. The smallest changes were observed in the commissural fibres, forceps major and forceps minor. In conclusion, our data suggest that DKI is sensitive to developmental changes in local microstructure and environment, and is particularly powerful to unravel developmental differences in major association fibres, such as the cingulum and superior longitudinal fasciculus.
authors.affiliation: Institute of Neuroscience and Medicine, 4, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany; Department of Neurology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany. Electronic address: f.grinberg@fz-juelich.de.
authors.forename: Farida
authors.initials: F
authors.lastname: Grinberg
authors.affiliation: Institute of Neuroscience and Medicine, 4, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany.
authors.forename: Ivan I
authors.initials: II
authors.lastname: Maximov
authors.affiliation: Institute of Neuroscience and Medicine, 4, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Farrher
authors.affiliation: Institute of Neuroscience and Medicine, 4, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Germany; JARA - BRAIN - Translational Medicine, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Neuner
authors.affiliation: Institute of Neuroscience and Medicine, 4, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Amort
authors.affiliation: Institute of Neuroscience and Medicine, 4, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany; Child Neuropsychology Section, Department of Child and Adolescent Psychiatry and Psychotherapy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Thönneßen
authors.affiliation: Child Neuropsychology Section, Department of Child and Adolescent Psychiatry and Psychotherapy, RWTH Aachen University, 52074 Aachen, Germany; Institute of Neuroscience and Medicine, 3, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
authors.forename: Eileen
authors.initials: E
authors.lastname: Oberwelland
authors.affiliation: Child Neuropsychology Section, Department of Child and Adolescent Psychiatry and Psychotherapy, RWTH Aachen University, 52074 Aachen, Germany; JARA - BRAIN - Translational Medicine, Germany; Institute of Neuroscience and Medicine, 3, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Konrad
authors.affiliation: Institute of Neuroscience and Medicine, 4, Forschungszentrum Juelich GmbH, 52425 Juelich, Germany; Department of Neurology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany; JARA - BRAIN - Translational Medicine, Germany.
authors.forename: N Jon
authors.initials: NJ
authors.lastname: Shah
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers; D002648:Child; D056324:Diffusion Tensor Imaging / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D066127:White Matter / Q000000981:diagnostic imaging* / Q000254:growth & development*
chemical_list: D015415:Biomarkers
keywords: Brain; Development; Diffusion kurtosis imaging; MRI; Microstructure; Non-Gaussian Diffusion