title: Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study.
abstract: Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than those of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study.
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, United States; Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Kilian M
authors.initials: KM
authors.lastname: Pohl
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States. Electronic address: edie@stanford.edu.
authors.forename: Edith V
authors.initials: EV
authors.lastname: Sullivan
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, United States.
authors.forename: Torsten
authors.initials: T
authors.lastname: Rohlfing
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, United States.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chu
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, United States; Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Dongjin
authors.initials: D
authors.lastname: Kwon
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, United States; Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: B Nolan
authors.initials: BN
authors.lastname: Nichols
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States; Veterans Affairs San Diego Healthcare System, La Jolla, CA, United States.
authors.forename: Susan F
authors.initials: SF
authors.lastname: Tapert
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cummins
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Thompson
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.
authors.forename: Ty
authors.initials: T
authors.lastname: Brumback
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, United States.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Colrain
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, United States.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Baker
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, United States.
authors.forename: Devin
authors.initials: D
authors.lastname: Prouty
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: De Bellis
authors.affiliation: Department of Radiology, Duke University School of Medicine, Durham, NC, United States.
authors.forename: James T
authors.initials: JT
authors.lastname: Voyvodic
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Duncan B
authors.initials: DB
authors.lastname: Clark
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Claudiu
authors.initials: C
authors.lastname: Schirda
authors.affiliation: Departments of Psychiatry and Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States.
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: Nagel
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, United States; Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
mesh_terms: D000293:Adolescent; D000428:Alcohol Drinking / Q000009:adverse effects*; D016880:Anisotropy; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D001931:Brain Mapping / Q000379:methods / Q000592:standards*; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D012727:Sex Characteristics; D066127:White Matter / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D055815:Young Adult
keywords: Adolescence; Cortex; Development; Diffusion tensor imaging; Ethnicity; Fractional anisotropy; Sex