White matter myelin abnormalities in schizophrenia

描述（由申请人提供）：有证据表明，大脑中白质连接的中断，特别是额叶和颞叶之间的连接，可能部分解释了精神分裂症的一些主要症状。利用弥散张量成像（DTI）一种对白质纤维束中断敏感的MR技术，研究报告了精神分裂症中的白质异常。然而，目前尚不清楚是什么神经病理过程导致了所观察到的变化（即轴突大小/直径、方向或髓鞘的改变）。目前的研究计划侧重于髓鞘，并试图确定精神分裂症中髓鞘含量异常导致DTI信号丢失的程度。更具体地说，这个项目的目的是使用磁化转移成像（MTI-对脑白质髓磷脂含量敏感的技术），结合已经获得的DTI扫描，以进一步调查诊断为精神分裂症患者和正常对照受试者的白质异常。所有受试者将接受MRI扫描，包括带和不带磁化转移脉冲的T1W图像。图像处理的第一步将包括创建所谓的磁化传递比（MTR）图像，描述归因于髓磷脂含量的信号。下一步，MTR图像将与已获取的DTI图像共同配准。接下来，将进行感兴趣区域（ROI）分析和体素统计分析，以检测精神分裂症患者的髓磷脂异常。对于ROI分析，我们将在之前的DTI研究中已经圈定并显示异常的脑纤维束（包括钩状束和扣带束）内计算平均MTR和MTR直方图。对于体素分析，所有受试者的MTR图像以及DTI图像将被扭曲到研究特定的模板，并通过体素统计分析进行组间体素。此外，年龄、性别、利手性、慢性、剂量和用药时间长短以及临床和选定的神经心理学症状等变量将纳入所有统计分析。这项研究的结果将使我们更好地了解精神分裂症的白质改变，并增加我们对精神分裂症连接异常的了解。

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.