Diffusion tensor imaging (DTI), which measures the magnitude of anisotropy of water diffusion in white matter, has recently been used to visualize and quantify parameters of neural tracts connecting brain regions. In order to investigate the developmental changes and sex and hemispheric differences of neural fibers in normal white matter, we used DTI to examine 52 healthy humans ranging in age from 2 months to 25 years. We extracted the following tracts of interest (TOIs) using the region of interest method: the corpus callosum (CC), cingulum hippocampus (CGH), inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF). We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). Approximate values and changes in growth rates of all DTI parameters at each age were calculated and analyzed using LOESS (locally weighted scatterplot smoothing). We found that for all TOIs, FA increased with age, whereas ADC, AD and RD values decreased with age. The turning point of growth rates was at approximately 6 years. FA in the CC was greater than that in the SLF, ILF and CGH. Moreover, FA, ADC and AD of the splenium of the CC (sCC) were greater than in the genu of the CC (gCC), whereas the RD of the sCC was lower than the RD of the gCC. The FA of right-hemisphere TOIs was significantly greater than that of left-hemisphere TOIs. In infants, growth rates of both FA and RD were larger than those of AD. Our data show that developmental patterns differ by TOIs and myelination along with the development of white matter, which can be mainly expressed as an increase in FA together with a decrease in RD. These findings clarify the long-term normal developmental characteristics of white matter microstructure from infancy to early adulthood.

Filley CM: Exploring white matter microstructure: new insights from diffusion tensor imaging. Neurology 2009;73:1718-1719.
Basser PJ, Mattiello J, LeBihan D: Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson B 1994;103:247-254.
Catani M, Howard RJ, Pajevic S, Jones DK: Virtual in vivo interactive dissection of white matter fasciculi in the human brain. Neuroimage 2002;17:77-94.
Underhill HR, Yuan C, Yarnykh VL: Direct quantitative comparison between cross-relaxation imaging and diffusion tensor imaging of the human brain at 3.0 T. Neuroimage 2009;47:1568-1578.
Yap QJ, Teh I, Fusar-Poli P, Sum MY, Kuswanto C, et al: Tracking cerebral white matter changes across the lifespan: insights from diffusion tensor imaging studies. J Neural Transm 2013;120:1369-1395.
Hermoye L, Saint-Martin C, Cosnard G, Lee SK, Kim J, et al: Pediatric diffusion tensor imaging: normal database and observation of the white matter maturation in early childhood. Neuroimage 2006;29:493-504.
Westlye LT, Walhovd KB, Dale AM, Bjornerud A, Due-Tonnessen P, et al: Life-span changes of the human brain white matter: diffusion tensor imaging (DTI) and volumetry. Cereb Cortex 2010;20:2055-2068.
Rorden C, Brett M: Stereotaxic display of brain lesions. Behav Neurol 2000;12:191-200.
Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, et al: Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 2006;31:1487-1505.
Yoshida S, Oishi K, Faria AV, Mori S: Diffusion tensor imaging of normal brain development. Pediatr Radiol 2013;43:15-27.
Mori S, Crain BJ, Chacko VP, van Zijl PC: Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 1999;45:265-269.
Xue R, van Zijl PC, Crain BJ, Solaiyappan M, Mori S: In vivo three-dimensional reconstruction of rat brain axonal projections by diffusion tensor imaging. Magn Reson Med 1999;42:1123-1127.
Mori S, Wakana S, Nagae-Poetscher LM, van Zijl PC: MRI Atlas of Human White Matter. Amsterdam, Elsevier, 2005.
Wakana S, Caprihan A, Panzenboeck MM, Fallon JH, Perry M, et al: Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage 2007;36:630-644.
Zhang Y, Schuff N, Jahng GH, Bayne W, Mori S, et al: Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease. Neurology 2007;68:13-19.
Cleveland WS: Robust locally weighted regression and smoothing scatterplots. J Am Stat Assoc 1979;74:829-836.
Lebel C, Walker L, Leemans A, Phillips L, Beaulieu C: Microstructural maturation of the human brain from childhood to adulthood. Neuroimage 2008;40:1044-1055.
Tanaka C, Matsui M, Uematsu A, Noguchi K, Miyawaki T: Developmental trajectories of the fronto-temporal lobes from infancy to early adulthood in healthy individuals. Dev Neurosci 2012;34:477-487.
Uematsu A, Matsui M, Tanaka C, Takahashi T, Noguchi K, et al: Developmental trajectories of amygdala and hippocampus from infancy to early adulthood in healthy individuals. PLoS One 2012;7:e46970.
Giorgio A, Watkins KE, Chadwick M, James S, Winmill L, et al: Longitudinal changes in grey and white matter during adolescence. Neuroimage 2010;49:94-103.
Seo Y, Wang ZJ, Ball G, Rollins NK: Diffusion tensor imaging metrics in neonates - a comparison of manual region-of-interest analysis vs. tract-based spatial statistics. Pediatr Radiol 2013;43:69-79.
Rose J, Vassar R, Cahill-Rowley K, Guzman XS, Stevenson DK, et al: Brain microstructural development at near-term age in very-low-birth-weight preterm infants: an atlas-based diffusion imaging study. Neuroimage 2014;86:244-256.
Gao W, Lin W, Chen Y, Gerig G, Smith JK, et al: Temporal and spatial development of axonal maturation and myelination of white matter in the developing brain. AJNR Am J Neuroradiol 2009;30:290-296.
Provenzale JM, Liang L, DeLong D, White LE: Diffusion tensor imaging assessment of brain white matter maturation during the first postnatal year. AJR Am J Roentgenol 2007;189:476-486.
Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, et al: Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A 2004;101:8174-8179.
Yakovlev PI, Lecours AR: The myelogenetic cycles of regional maturation of the brain; in Minkowski A (ed): Regional Development of the Brain in Early Life. Oxford, Blackwell Scientific, 1967, pp 3-70.
Lebel C, Gee M, Camicioli R, Wieler M, Martin W, et al: Diffusion tensor imaging of white matter tract evolution over the lifespan. Neuroimage 2012;60:340-352.
Schmithorst VJ, Holland SK, Dardzinski BJ: Developmental differences in white matter architecture between boys and girls. Hum Brain Mapp 2008;29:696-710.
Abe O, Aoki S, Hayashi N, Yamada H, Kunimatsu A, et al: Normal aging in the central nervous system: quantitative MR diffusion-tensor analysis. Neurobiol Aging 2002;23:433-441.
Ota M, Obata T, Akine Y, Ito H, Ikehira H, et al: Age-related degeneration of corpus callosum measured with diffusion tensor imaging. Neuroimage 2006;31:1445-1452.
Schneiderman JS, Buchsbaum MS, Haznedar MM, Hazlett EA, Brickman AM, et al: Diffusion tensor anisotropy in adolescents and adults. Neuropsychobiology 2007;55:96-111.
Park HJ, Westin CF, Kubicki M, Maier SE, Niznikiewicz M, et al: White matter hemisphere asymmetries in healthy subjects and in schizophrenia: a diffusion tensor MRI study. Neuroimage 2004;23:213-223.
Hasan KM, Kamali A, Abid H, Kramer LA, Fletcher JM, et al: Quantification of the spatiotemporal microstructural organization of the human brain association, projection and commissural pathways across the lifespan using diffusion tensor tractography. Brain Struct Funct 2010;214:361-373.
Travers BG, Adluru N, Ennis C, Tromp do PM, Destiche D, et al: Diffusion tensor imaging in autism spectrum disorder: a review. Autism Res 2012;5:289-313.
Fitzsimmons J, Kubicki M, Shenton ME: Review of functional and anatomical brain connectivity findings in schizophrenia. Curr Opin Psychiatry 2013;26:172-187.
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