MR Brain Diffusion Tensor Imaging in Schizophrenia

描述(由申请人提供)： 这项建议的长期目标是通过应用快速发展的神经成像领域的活体神经成像工具来了解精神分裂症患者大脑异常的性质。短期目标是使用磁共振(MR)扩散张量成像(DTI)评估白质异常，DTI是一种相对较新的神经成像工具，可以揭示白质的物理属性。特别值得注意的是，这种新的成像工具是唯一可用于评估精神分裂症白质纤维束异常的活体工具，虽然受到新研究领域预期问题的困扰，但它仍然是可用于评估精神分裂症白质变化的最有前途和最强大的工具。这项成像技术将用于研究额-颞白质连接、大脑半球间白质连接、丘脑-额叶纤维束和额顶白质连接中的白质异常。研究对象为右撇子精神分裂症患者(包括慢性精神分裂症和首发精神分裂症)和年龄、性别、利手、父母社会经济地位相匹配的对照组。研究样本将包括50名慢性患者、110名首发患者和160名对照，在5年的赠款期间进行基线研究，并在一年后的随访中再次研究50名首发患者和50名对照。MR DTI感兴趣区域和光刻测量将用于量化上述纤维束中的各向异性扩散(水运动的方向性程度，以分数各向异性衡量)和扩散率(所有方向的平均扩散)。还将在一年后评估首发患者和对照组的纵向变化，以确定与对照组相比，首发患者在这段时间内脑白质的进行性变化。具体预测是关于认知和DTI异常(例如，语义启动异常和弓状束异常之间的相关性)。此外，另一项衡量白质健康和完整性的指标--大脑半球间转移时间任务(IHTT)--将被包括在一项视觉诱发电位研究中，该研究预测，精神分裂症患者的IHTT效率将受到影响。也有人预测，更长的IHTT和更少的不对称性，将与大脑中最大的白质束--胼胝体后部的DTI测量相关，而这又将与处理速度的测量相关。纵向设计也是IHTT措施的一部分，即首发患者和对照将在一年后进行评估。对精神分裂症患者进行磁共振弥散张量成像的研究，将有助于进一步了解精神分裂症患者脑白质纤维束的异常情况，为了解精神分裂症的神经病理机制，最终达到更好、更合理的治疗提供关键的一环。 公共卫生相关性： 精神分裂症是一种破坏性的疾病，影响到近1%的总人口和40%的退伍军人精神卫生保健费用(http://www.va.gov).因此，了解这种疾病对退伍军人管理局的任务至关重要。磁共振(MR)扩散张量成像(DTI)将用于研究精神分裂症患者脑白质(WM)的异常。到目前为止，常规的MR发现报告了灰质异常，但很少有研究报告WM异常。随着弥散张量成像的出现，现在可以研究对精神分裂症很重要的西医区。DTI图像将从慢性和首发患者以及对照组获得。还将包括处理速度的测量，并将评估相关的认知和症状测量，以确定WM、认知异常、临床症状和处理速度之间的关联。这项建议将导致关于WM异常以及认知和临床相关性的新发现，这反过来将最终导致对这种毁灭性疾病的更好和更合理的治疗。

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to understand the nature of brain abnormalities in schizophrenia by applying in vivo neuroimaging tools from the rapidly developing field of neuroimaging. The short-term objective is to evaluate white matter abnormalities using Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI), a relatively new neuroimaging tool that reveals the physical properties of white matter. Of particular note, this new imaging tool is the only in vivo tool available to evaluate white matter fiber bundle abnormalities in schizophrenia, and, while plagued by problems expected in a new field of inquiry, it is still the most promising and powerful tool available to evaluate white matter alterations in schizophrenia. This imaging technique will be used to investigate white matter abnormalities in fronto-temporal white matter connections, interhemispheric white matter connections, thalamo-frontal fiber tracts, and frontal-parietal white matter connections. The subject sample will be right-handed patients with schizophrenia (both chronic and first episode) and age, gender, handedness, and parental socioeconomic status group matched controls. The study sample will be comprised of 50 chronic patients,110 first episode patients, and 160 controls studied at baseline over the 5 year grant period, and 50 first episode and 50 controls studied again at follow up one year later. MR DTI region of interest and tractography measures will be used to quantify anisotropic diffusion (degree of directionality of water movement, measured as fractional anisotropy) and diffusivity (average diffusion in all directions) in the aforementioned fiber bundles. Longitudinal changes will also be evaluated one year later in first episode patients and controls in order to determine progressive changes in white matter over this time period in first episode patients compared with controls. Specific predictions are made with respect to cognitive and DTI abnormalities (e.g., correlations between semantic priming abnormalities and arcuate fasciculus abnormalities). In addition another measure of white matter health and integrity, the interhemispheric transfer time task (IHTT), will be included in a visual evoked potential study, where it is predicted that IHTT efficiency will be compromised in schizophrenia. It is also predicted that longer IHTT, and decreased asymmetry, will be correlated with DTI measures in posterior portions of the corpus callosum, the largest white matter tract in the brain, which, in turn, will be correlated with measures of speed of processing. A longitudinal design is also a part of the IHTT measures, i.e., first episode patients and controls will be evaluated one year later. The investigation of MR DTI in schizophrenia will lead to a further understanding of white matter fiber tract abnormalities in this disorder, which will add a key link to understanding the neuropathology of schizophrenia, and ultimately to better and more rational treatment. PUBLIC HEALTH RELEVANCE: Schizophrenia is a devastating disorder that affects close to 1% of the general population and 40% of all VA mental healthcare costs (http://www.va.gov). Understanding this disorder is thus critical to the VA mission. Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI) will be used to investigate white matter (WM) brain abnormalities in schizophrenia. Heretofore, conventional MR findings reported gray matter abnormalities, but few studies reported WM abnormalities. With the advent of DTI, WM tracts important to schizophrenia can now be investigated. DTI images will be acquired from chronic and first-episode patients, as well as controls. A measure of processing speed will also be included and relevant cognitive and symptom measures will be evaluated to determine associations among WM, cognitive abnormalities, clinical symptoms, and processing speed. This proposal will lead to new findings regarding WM abnormalities and cognitive and clinical correlates, which, in turn, will ultimately lead to better and more rationale treatment of this devastating disorder.