title: White Matter Changes of Neurite Density and Fiber Orientation Dispersion during Human Brain Maturation.
abstract: Diffusion tensor imaging (DTI) studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI) is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI) and neurite density index (NDI). In this study, we apply NODDI to 66 healthy controls aged 7-63 years to investigate changes of ODI and NDI with brain maturation, with comparison to standard DTI metrics. Using both region-of-interest and voxel-wise analyses, we find that NDI exhibits striking increases over the studied age range following a logarithmic growth pattern, while ODI rises following an exponential growth pattern. This novel finding is consistent with well-established age-related changes of FA over the lifespan that show growth during childhood and adolescence, plateau during early adulthood, and accelerating decay after the fourth decade of life. Our results suggest that the rise of FA during the first two decades of life is dominated by increasing NDI, while the fall in FA after the fourth decade is driven by the exponential rise of ODI that overcomes the slower increases of NDI. Using partial least squares regression, we further demonstrate that NODDI better predicts chronological age than DTI. Finally, we show excellent test-retest reliability of NODDI metrics, with coefficients of variation below 5% in all measured regions of interest. Our results support the conclusion that NODDI reveals biologically specific characteristics of brain development that are more closely linked to the microstructural features of white matter than are the empirical metrics provided by DTI.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Yi Shin
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America; Program in Bioengineering, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Julia P
authors.initials: JP
authors.lastname: Owen
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Pojman
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Tony
authors.initials: T
authors.lastname: Thieu
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Polina
authors.initials: P
authors.lastname: Bukshpun
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Mari L J
authors.initials: ML
authors.lastname: Wakahiro
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Berman
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Timothy P L
authors.initials: TP
authors.lastname: Roberts
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America; Program in Bioengineering, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Srikantan S
authors.initials: SS
authors.lastname: Nagarajan
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Elliott H
authors.initials: EH
authors.lastname: Sherr
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America; Program in Bioengineering, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Pratik
authors.initials: P
authors.lastname: Mukherjee
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000254:growth & development*; D001931:Brain Mapping; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers; D016501:Neurites; D015203:Reproducibility of Results; D066127:White Matter / Q000254:growth & development*; D055815:Young Adult