Comparing free water imaging and magnetization transfer measurements in schizophrenia

René C.W Mandl,Ofer Pasternak,Wiepke Cahn,Marek Kubicki,René S Kahn,Martha E Shenton,Hilleke E Hulshoff Pol

doi:10.1016/j.schres.2014.09.046

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.

Highlights

The etiology of schizophrenia is still unknown there is compelling evidence that white matter in the brain is implicated (Flynn et al, 2003; Friston and Frith, 1995; Hulshoff Pol et al, 2004; Kubicki et al, 2005a; Shenton et al, 2001; Voineskos et al, 2010)
Using the fiber-based analysis we found statistically significantly higher magnetization transfer ratio (MTR) values for schizophrenia patients in the right uncinate fasciculus, the right inferior fronto-occipital fasciculus and the right arcuate fasciculus (See Figure 2)
We find increased MTR values in the uncinate and arcuate fasciculus in patients with schizophrenia

Summary

Introduction

The etiology of schizophrenia is still unknown there is compelling evidence that white matter in the brain is implicated (Flynn et al, 2003; Friston and Frith, 1995; Hulshoff Pol et al, 2004; Kubicki et al, 2005a; Shenton et al, 2001; Voineskos et al, 2010). Magnetic resonance imaging (MRI) techniques such as diffusion weighted imaging (DWI) (Le Bihan and Breton, 1985; Stejskal E.O. and J.E., 1965) --- or when a tensor is used to model the diffusion profile of the water molecules, referred to as diffusion tensor imaging (DTI) (Basser, 1995) --- have been extensively used to study schizophrenia, with varying results These differences in results may be due to differences in patient populations, MRI field strengths, MRI acquisition sequences used, and/or analysis techniques, but most likely are a result of a combination of these factors (Kubicki et al, 2013). To compare diffusion profiles between subjects, a number of scalar measures have been introduced to describe certain aspects of the diffusion profile These include fractional anisotropy (FA) (Basser and Pierpaoli, 1996) and mean diffusivity (MD), which represent the two most frequently measures used. Differences in fiber directionality, level of myelination and axonal diameter and, importantly, the degree of partial volume between different tissue types, will all result in differences in FA as well as MD (De Santis et al, 2014)

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