title: Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression.
abstract: Diffusion tensor imaging (DTI) holds promise for developing our understanding of white-matter pathology in major depressive disorder (MDD). Variable findings in DTI-based investigations of MDD, however, have thwarted development of this literature. Effects of extra-cellular free-water on the sensitivity of DTI metrics could account for some of this inconsistency. Here we investigated whether applying a free-water correction algorithm to DTI data could improve the sensitivity to detect clinical effects using DTI metrics. Only after applying this correction, we found: a) significantly decreased fractional anisotropy and axial diffusivity (AD) in the left inferior fronto-occipital fasciculus (IFOF) in MDD; and b) increased self-reported stress that significantly correlated with decreased IFOF AD in depression. We estimated and confirmed the robustness of differences observed between free-water corrected and uncorrected approaches using bootstrapping. We conclude that applying a free-water correction to DTI data increases the sensitivity of DTI-based metrics to detect clinical effects in MDD.
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bergamino
authors.affiliation: Department of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Pasternak
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK, USA.
authors.forename: Madison
authors.initials: M
authors.lastname: Farmer
authors.affiliation: Department of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK, USA; Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linköping, Sweden.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Hamilton
mesh_terms: D000328:Adult; D000465:Algorithms; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D003865:Major Depressive Disorder / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013315:Stress, Psychological / Q000473:pathology*; D014867:Water; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
chemical_list: D014867:Water
keywords: Axial diffusivity; Diffusion tensor imaging; Fractional anisotropy; Free-water corrected DTI; Major depressive disorder; Tract-based spatial statistics