title: Comparing free water imaging and magnetization transfer measurements in schizophrenia.
abstract: Diffusion weighted imaging (DWI) has been extensively used to study the microarchitecture of white matter in schizophrenia. However, popular DWI-derived measures such as fractional anisotropy (FA) may be sensitive to many types of pathologies, and thus the interpretation of reported differences in these measures remains difficult. Combining DWI with magnetization transfer ratio (MTR) - a putative measure of white matter myelination - can help us reveal the underlying mechanisms. Previous findings hypothesized that MTR differences in schizophrenia are associated with free water concentrations, which also affect the DWIs. In this study we use a recently proposed DWI-derived method called free-water imaging to assess this hypothesis. We have reanalyzed data from a previous study by using a fiber-based analysis of free-water imaging, providing a free-water fraction, as well as mean diffusivity and FA corrected for free-water, in addition to MTR along twelve major white matter fiber bundles in 40 schizophrenia patients and 40 healthy controls. We tested for group differences in each fiber bundle and for each measure separately and computed correlations between the MTR and the DWI-derived measures separately for both groups. Significant higher average MTR values in patients were found for the right uncinate fasciculus, the right arcuate fasciculus and the right inferior-frontal occipital fasciculus. No significant results were found for the other measures. No significant differences in correlations were found between MTR and the DWI-derived measures. The results suggest that MTR and free-water imaging measures can be considered complementary, promoting the acquisition of MTR in addition to DWI to identify group differences, as well as to better understand the underlying mechanisms in schizophrenia.
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands. Electronic address: r.mandl@umcutrecht.nl.
authors.forename: René C W
authors.initials: RC
authors.lastname: Mandl
authors.affiliation: Harvard Medical School, Brigham and Women's Hospital, Departments of Psychiatry and Radiology, Boston, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Pasternak
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands.
authors.forename: Wiepke
authors.initials: W
authors.lastname: Cahn
authors.affiliation: Harvard Medical School, Brigham and Women's Hospital, Departments of Psychiatry and Radiology, Boston, USA.
authors.forename: Marek
authors.initials: M
authors.lastname: Kubicki
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands.
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Harvard Medical School, Brigham and Women's Hospital, Departments of Psychiatry and Radiology, Boston, USA; VA Boston Healthcare System, Brockton, MA, USA.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands.
authors.forename: Hilleke E
authors.initials: HE
authors.lastname: Hulshoff Pol
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000473:pathology*; D014867:Water / Q000378:metabolism*; D066127:White Matter / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D014867:Water
keywords: Fiber based analysis; Free water imaging; Human brain; MTR; Schizophrenia; White matter