Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Nov 30:10:336-42.
doi: 10.1016/j.nicl.2015.11.020. eCollection 2016.

Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression

Maurizio Bergamino  1 , Ofer Pasternak  2 , Madison Farmer  1 , Martha E Shenton  3 , J Paul Hamilton  4
Affiliations

Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression

Maurizio Bergamino et al. Neuroimage Clin. .

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.

Keywords: Axial diffusivity; Diffusion tensor imaging; Fractional anisotropy; Free-water corrected DTI; Major depressive disorder; Tract-based spatial statistics.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Clusters where decrements in FA and AD in the MDD relative to the HC group were found when we used the free-water corrected maps. The skeletonized map is shown in blue. The figure is in radiological convention. The MNI coordinates of the centers of mass for AD and FA clusters are (x, y, z): − 39, − 46, − 1 and − 39, − 43, − 1, respectively.
Fig. 2
Fig. 2
Top: For each group, per-subject FA (A) and AD (B) values from clusters in which a between-groups difference was detected using the free-water correction procedure. For comparison, values derived from uncorrected data are also shown. Bottom: For data from these same clusters, bootstrapping-derived distributions of difference in Cohen's d obtained with versus without applying free-water correction prior to estimating FA (C) and AD (D). Dashed lines represent boundaries of middle 95th percentile of distribution of Cohen's d with minus without free-water correction; that the middle 95th percentile does not intersect with zero indicates the reliability of the difference in Cohen's d.
Fig. 3
Fig. 3
Top: Pearson's correlation between AD values from the cluster in which a between-groups difference was detected using the free-water correction procedure, and (A) PSWQ, (B) PDSS, and (C) PSS scores. Bottom: The histograms derived from the bootstrap procedure for assessing the reliability of differences in AD correlations with the PSWQ (D), PDSS (E), and PSS (F) when the free-water correction either was or was not applied. Dashed lines represent boundaries of middle 95th percentile of distribution of r with minus without free-water correction; that the middle 95th percentile does not intersect with zero in D and F indicates the reliability of the difference in r statistics.
See this image and copyright information in PMC

References

    1. Alexander A.L., Lee J.E., Lazar M., Field A.S. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007;4:316–329. - PMC - PubMed
    1. Beck A.T., Rush A.J., Shaw B.F., Emery G. 1979. Cognitive Therapy of Depression.
    1. Behrens T.E., Woolrich M.W., Jenkinson M., Johansen-Berg H., Nunes R.G., Clare S., Matthews P.M., Brady J.M., Smith S.M. Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn. Reson. Med. 2003;50:1077–1088. - PubMed
    1. Berlot R., Metzler-Baddeley C., Jones D.K., O'Sullivan M.J. CSF contamination contributes to apparent microstructural alterations in mild cognitive impairment. NeuroImage. 2014;92:27–35. - PMC - PubMed
    1. Bowley M.P., Drevets W.C., Ongur D., Price J.L. Low glial numbers in the amygdala in major depressive disorder. Biol. Psychiatry. 2002;52:404–412. - PubMed

Publication types