DTI AND MTI STUDIES IN SCHIZOPHRENIA

DTI 和 MTI 对精神分裂症的研究

• 批准号: 7718114
• 负责人: MONTE Stuart BUCHSBAUM
• 金额: $ 1.03万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718114
• 关键词: Age; Anisotropy; Area; Behavioral; Blood specimen; Brain; Brain region; Brodmann' s area; Chronic; Clinical; Cognitive; Compatible; Competence; Complex; Computer Retrieval of Information on Scientific Projects Database; Corpus Callosum; Corpus striatum structure; DNA; Data; Diffusion; Fiber; Funding; Genes; Glucose; Grant; Health; Hyperactive behavior; Image; Individual; Institution; Interruption; Lead; Length; Limbic System; Localized; Measurement; Measures; Medical; Metabolic; Methods; Myelin; Numbers; Oligodendroglia; Pathway interactions; Patients; Pattern; Performance; Positron-Emission Tomography; Prefrontal Cortex; Rate; Recruitment Activity; Relative (related person); Reporting; Research; Research Personnel; Resources; Sampling; Sampling Studies; Scanning; Schizophrenia; Severities; Source; Structure; Symptoms; Testing; Text; Thalamic structure; United States National Institutes of Health; Work; basal forebrain; cohort; follow-up; frontal lobe; interest; programs; sex; white matter

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 1/22/2008 Alterations in connectivity among brain regions such as the frontal lobe, basal forebrain and limbic system have been proposed as network deficits in schizophrenia. The multiregional aspects of the hypothesized problems in connectivity implicate a possible deficit in white matter that could lead to the rerouting or interruption of a number of specific brain circuits. A global deficit in myelin in schizophrenia may also produce a pattern of distributed multiregional deficits compatible with the complex, not clearly localizing, behavioral and cognitive disorganization in schizophrenia. Alteration in numbers, distribution, and ultrastructural integrity of oligodendrocytes, key white matter components, has recently been reported in the prefrontal cortex in schizophrenia, consistent with our original diffusion tensor findings of diminished anisotropy in frontal white matter and our replication of this in the first funding period of this project. To extend our findings of white matter abnormalities in schizophrenia we plan four projects: 1) we will complete a longitudinal sample study with follow-up scans 3 yrs in a cohort of patients with schizophrenia and controls where we have already acquired diffusion tensor and structural images from the already acquired sample of 3T longitudinal sample (240 subjects - 125 patients with schizophrenia and 115 matched controls); 2) We will also acquire FDG-PET with absolute glucose quantification on a cohort of 32 unmedicated patients with schizophrenia and 32 age- and sex-matched controls to further develop our initial finding of increased white matter relative metabolic rate in schizophrenia, we will develop exploratory voxel-by-voxel correlations between anisotropy and glucose metabolic rate; 3) We will exploit our recently developed tract tracing programs to assess the specific tract directions and termination points for cingulate, thalamic, striatal, and callosal fibers in the prefrontal cortex; 4) We will share white matter anisotropy and volumetric measures with Projects 1, 2, 3 and 5 and Core B in order to facilitate and inform their potential choice of brain areas to be examined. Taken together, these aims will allow us to obtain the most reliable, valid, functionally different, and informative white matter assessments to confirm specific thalamo-frontal, fronto-striatal and cingulate pathway abnormalities in schizophrenia. Hypothesis: This project is an extension of work completed during the first five years of the Conte Center grant (August 2003-July 2007) (GCO #: 01-1186). During the next funding period we will perform follow-up behavioral and imaging assessments on the cohort of subjects recruited under the previous funding period of our Conte Center recruited through July 31, 2007. In addition we will perform FDG-PET on a newly recruited cohort of subjects in order to further evaluate the white matter hyperactivity findings presented above. We will use pilot data previously collected on an independent cohort to help guide the selection of specific white matter tracts and tract-tracing parameters. The specific Aims of this project are as follows: Aim 1: We will acquire follow-up DTI scans on the chronic and first episode schizophrenic and matched control cohorts scanned with DTI on the 3T machine during the previous funding cycle of our Conte Center (August 2003 - July 2003). In addition, measures of symptom severity, cognitive performance, functional competence and assessments of medical health will be collecteed for exploratory correlational analyses with white matter tract measures. Pilot data on both diffusion tensor and structural images from the previous scans collected under the Conte Center, in addition to other independent DTI data will be used to select the most promising white matter tract regions of interest and cortical areas of volumetric loss. In addition we will collect blood samples on all subjects recruited for follow-up DTI scans for DNA analyses to be conducted by the investigators of Project 2 (O'Donovan). Aim 2: We will acquire FDG-PET (Fluoro-deoxy-glucose Positron Emission Tomography) with absolute glucose quantification and DTI scans on a newly identified cohort of 32 un-medicated subjects with schizophrenia and 32 age- and sex-matched controls to test the hypothesis that individuals with low anisotropy in cingulate, frontal white matter, corpus callosum and the superior longitudinal fasciculus will have high metabolic rates in these structures, consistent with disorganized and therefore inefficient white matter. We will develop exploratory voxel-by-voxel correlations between anisotropy and glucose metabolic rate. In addition we will collect blood samples on all 64 subjects recruited for FDG-PET scans for DNA analyses to be conducted by the investigators of Project 2 (O'Donovan). Aim 3: We will analyze all DTI images and clinical measures collected during the previous funding cycle of the Conte Center grant (August 2003-July 2007 in detail using new tractography methods. The first of these methods is currently operational (explained in detail in the project text). We will test the hypothesis that Prefrontal cortex organization of thalamocortical fibers will be abnormal in schizophrenia with the 12 Brodmann areas receiving a different proportion and direction of traced tracts. Aim 4: We will share diffusion tensor FA data obtained from traced regions and tract number and length measurements with Projects 1, 2, 3 and the Brain Bank Core of the Conte Center in order to facilitate and inform on the selection of interesting brain regions for neuroanatomical studies and to explore the relationships between these imaging findings and important white matter genes identified by Project 2..

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 2008年1月22日 额叶、基底前脑和边缘系统等大脑区域之间连接性的改变被认为是精神分裂症的网络缺陷。假设的连接问题的多区域方面暗示白质可能存在缺陷，这可能导致许多特定大脑回路的重新路由或中断。精神分裂症的髓鞘质整体缺陷也可能产生一种分布式多区域缺陷模式，与精神分裂症复杂的、不明确局部的行为和认知紊乱相一致。最近报道了精神分裂症患者前额皮质中少突胶质细胞（关键白质成分）数量、分布和超微结构完整性的改变，这与我们最初的额叶白质各向异性减弱的扩散张量发现一致，并且我们在第一个研究中对此进行了复制。本项目资助期限。 为了扩展我们对精神分裂症白质异常的发现，我们计划了四个项目： 1) 我们将在一组精神分裂症患者和对照组中完成一项纵向样本研究，并进行 3 年的随访扫描，其中我们已经从已采集的 3T 纵向样本（240 名受试者 - 125 名患者）中获取了弥散张量和结构图像患有精神分裂症和 115 名匹配对照）； 2) 我们还将对 32 名未接受药物治疗的精神分裂症患者和 32 名年龄和性别匹配的对照组进行 FDG-PET 绝对葡萄糖定量，以进一步发展我们关于精神分裂症白质相对代谢率增加的初步发现，我们将开发探索各向异性和葡萄糖代谢率之间逐体素的相关性； 3）我们将利用我们最近开发的束追踪程序来评估前额皮质中扣带回、丘脑、纹状体和胼胝体纤维的特定束方向和终止点； 4) 我们将与项目 1、2、3 和 5 以及核心 B 分享白质各向异性和体积测量，以促进和告知他们对要检查的大脑区域的潜在选择。总而言之，这些目标将使我们能够获得最可靠、有效、功能不同且信息丰富的白质评估，以确认精神分裂症中特定的丘脑-额叶、额-纹状体和扣带回通路异常。 假设： 该项目是 Conte 中心拨款的前五年（2003 年 8 月至 2007 年 7 月）（GCO 号：01-1186）期间完成的工作的延伸。在下一个资助期内，我们将对 Conte 中心上一个资助期（截至 2007 年 7 月 31 日）招募的受试者队列进行后续行为和影像评估。此外，我们将对新招募的队列进行 FDG-PET受试者以进一步评估上述白质过度活跃的发现。 我们将使用之前在独立队列中收集的试点数据来帮助指导特定白质束和束追踪参数的选择。该项目的具体目标如下： 目标 1：我们将获得在我们 Conte 中心的上一个资助周期（2003 年 8 月 - 2003 年 7 月）期间在 3T 机器上使用 DTI 扫描的慢性和首发精神分裂症患者和匹配对照队列的后续 DTI 扫描。此外，还将收集症状严重程度、认知表现、功能能力和医疗健康评估的测量结果，用于与白质束测量的探索性相关分析。除了其他独立的 DTI 数据之外，Conte 中心收集的先前扫描的扩散张量和结构图像的试点数据将用于选择最有希望的白质束感兴趣区域和体积损失的皮质区域。 此外，我们还将收集所有受试者的血液样本，以进行后续 DTI 扫描，以便由项目 2 (O'Donovan) 的研究人员进行 DNA 分析。 目标 2：我们将对新确定的 32 名未接受药物治疗的精神分裂症受试者和 32 名年龄和性别匹配的对照组进行测试，获得 FDG-PET（氟脱氧葡萄糖正电子发射断层扫描），并进行绝对葡萄糖定量和 DTI 扫描假设扣带回、额叶白质、胼胝体和上纵束各向异性较低的个体将具有较高的各向异性这些结构的代谢率与无序且低效的白质一致。我们将开发各向异性和葡萄糖代谢率之间探索性的逐体素相关性。此外，我们还将收集 64 名招募进行 FDG-PET 扫描的受试者的血液样本，以供项目 2 (O'Donovan) 的研究人员进行 DNA 分析。 目标 3：我们将使用新的纤维束成像方法详细分析在 Conte 中心拨款的上一个资助周期（2003 年 8 月至 2007 年 7 月）期间收集的所有 DTI 图像和临床测量结果。第一种方法目前正在运行（详细说明请参阅项目文本）我们将检验这样的假设：精神分裂症患者的丘脑皮层纤维的前额皮层组织会出现异常，12 个布罗德曼区域会受到不同的比例和影响。追踪区域的方向。 目标 4：我们将与项目 1、2、3 和 Conte 中心的脑库核心共享从追踪区域以及束数量和长度测量中获得的扩散张量 FA 数据，以促进和告知感兴趣的大脑区域的选择神经解剖学研究并探索这些成像结果与项目 2 确定的重要白质基因之间的关系。