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Re-examining Age-related Differences in White Matter Microstructure with Free-water Corrected Diffusion Tensor Imaging

1Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada. Electronic address:
2Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
3MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Elsevier Science
Publication Date:
Neurobiol Aging
Volume Number:
Neurobiol Aging. 2018 Nov;71:161-70.
PubMed ID:
Diffusion tensor imaging, Free water, Healthy adult aging, Magnetic resonance imaging, White matter
Appears in Collections:
P01 NS058793/NS/NINDS NIH HHS/United States
R01 MH108574/MH/NIMH NIH HHS/United States
R01 AG042512/AG/NIA NIH HHS/United States
P41 EB015902/EB/NIBIB NIH HHS/United States
R01 NR010827/NR/NINR NIH HHS/United States
Generated Citation:
Chad J.A., Pasternak O., Salat D.H., Chen J.J. Re-examining Age-related Differences in White Matter Microstructure with Free-water Corrected Diffusion Tensor Imaging. Neurobiol Aging. 2018 Nov;71:161-70. PMID: 30145396. PMCID: PMC6179151.
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Diffusion tensor imaging (DTI) has been used extensively to investigate white matter (WM) microstructural changes during healthy adult aging. However, WM fibers are known to shrink throughout the lifespan, leading to larger interstitial spaces with age. This could allow more extracellular free water molecules to bias DTI metrics, which are relied upon to provide WM microstructural information. Using a cohort of 212 participants, we demonstrate that WM microstructural changes in aging are potentially less pronounced than previously reported once the free water compartment is eliminated. After free water elimination, DTI parameters show age-related differences that match histological evidence of myelin degradation and debris accumulation. The fraction of free water is further shown to associate better with age than any of the conventional DTI parameters. Our findings suggest that DTI analyses involving free water are likely to yield novel insight into retrospective re-analysis of data and to answer new questions in ongoing DTI studies of brain aging.