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Brain Behav. 2017 Jan 14;7(2):e00615. doi: 10.1002/brb3.615. eCollection 2017 Feb.

Reproducibility of tract-based white matter microstructural measures using the ENIGMA-DTI protocol.

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Department of PsychiatryUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA; Research Imaging InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA.
Department of Psychiatry Maryland Psychiatric Research Center University of Maryland School of Medicine Baltimore MD USA.
Department of PsychiatryMaryland Psychiatric Research CenterUniversity of Maryland School of MedicineBaltimoreMDUSA; Russell H. Morgan Department of Radiology and Radiological ScienceJohns Hopkins UniversityBaltimoreMDUSA.
Oxford Centre for Functional MRI of the BrainUniversity of OxfordOxfordUK; Department of PsychiatryYale University School of MedicineNew HavenCTUSA.
Department of Psychiatry University of Texas Health Science Center at San Antonio San Antonio TX USA.
Imaging Genetics Center, Stevens Neuroimaging and Informatics Institute Keck School of Medicine of USC Marina del Rey CA USA.
Department of Neurology 59th Medical Wing Lackland AFB TX USA.
Department of Neuroradiology 59th Medical Wing Lackland AFB TX USA.



In preparation for longitudinal analyses of white matter development in youths with family histories of substance use disorders (FH+) or without such histories (FH-), we examined the reproducibility and reliability of global and regional measures of fractional anisotropy (FA) values, measured using the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA)-diffusion tensor imaging (DTI) protocol. Highly reliable measures are necessary to detect any subtle differences in brain development.


First, we analyzed reproducibility data in a sample of 12 healthy young adults (ages 20-28) imaged three times within a week. Next, we calculated the same metrics in data collected 1-year apart in the sample of 68 FH+ and 21 FH- adolescents. This is a timeframe where within subject changes in white matter microstructure are small compared to between subject variance. Reproducibility was estimated by examining mean coefficients of variation (MCV), mean absolute differences (MAD), and intraclass correlations (ICC) for global and tract-specific FA values.


We found excellent reproducibility for whole-brain DTI-FA values and most of the white matter tracts, except for the corticospinal tract and the fornix in both adults and youths. There was no significant effect of FH-group on reproducibility (= .4). Reproducibility metrics were not significantly different between adolescents and adults (all > .2). In post hoc analyses, the reproducibility metrics for regional FA values showed a strong positive correlation (= .6) with the regional FA heritability measures previously reported by ENIGMA-DTI.


Overall, this study demonstrated an excellent reproducibility of ENIGMA-DTI FA, positing it as viable analysis tools for longitudinal studies and other protocols that repeatedly assess white matter microstructure.


ENIGMA‐DTI; diffusion tensor imaging; fractional anisotropy; reproducibility; white matter microstructure

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