White matter myelin abnormalities in schizophrenia

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DESCRIPTION (provided by applicant): Evidence suggests that a disruption in white matter connectivity in the brain, especially between the frontal and temporal lobes, may partly explain some of the primary symptoms of schizophrenia. Studies using Diffusion Tensor Imaging (DTI) an MR technique sensitive to the white matter fiber tract disruptions, report white matter abnormalities in schizophrenia. It is, however, not clear what neuropathological processes are responsible for the changes observed (i.e., alterations in axonal size/diameter, orientation, or in myelin sheath). The current research proposal focuses on the myelin sheath, and seeks to determine the extent to which myelin content abnormalities in schizophrenia contribute to the loss of the DTI signal. More specifically, the aim of this project is to use Magnetization Transfer Imaging (MTI- technique sensitive to the myelin content of the brain white matter), in combination with already acquired DTI scans, in order to investigate further white matter abnormalities in patients diagnosed with schizophrenia and in normal control subjects. All subjects will undergo MRI scans that include T1W images with and without magnetization transfer pulse. The first step of the image processing will include creation of so-called magnetization transfer ratio (MTR) images that describe signal attributed to myelin content. In the next step, MTR images will be co-registered with already acquired DTI images. Next, Region of Interest (ROI) analysis as well as voxel wise statistical analysis will be performed to detect myelin abnormalities in schizophrenia. For the ROI analysis, mean MTR and MTR histograms will be calculated within brain fiber tracts that have been already delineated and showed abnormalities in the previous DTI studies (including uncinate fasciculus and cingulate fasciculus). For the voxel wise analysis, MTR images as well as DTI images of all subjects, will be warped to the study specific template and subjected to the between group voxel by voxel statistical analysis. In addition, variables such as age, gender, handedness, chronicity, dose and length of medication as well as clinical and selected neuropsychological symptoms will be included in all statistical analyses. Results from this study will allow us to understand better white matter alterations in schizophrenia, and add to what we know about connectivity abnormalities in schizophrenia.