Novel Diffusion MRI Analyses of White Matter in Schizophrenia

描述(由申请人提供)：本申请是完成第一个周期的R01的竞争性续签。总体目标是使用体内磁共振扩散成像 (DMRI)研究精神分裂症(SZ)的脑白质(WM)病理。微结构WM病理测量有可能对新的SZ治疗策略(抗炎药物、促进细胞再生的药物、髓鞘保护药物等)产生巨大影响。前一个项目周期的重点是扩散张量成像(DTI)和高角分辨率扩散成像(HARDI)模型，并证实深圳地区的WM存在微妙的异常。在这项新的提案中，我们计划利用先进的dMRI扫描和分析技术开发更灵敏的组织微结构探针，以帮助探索细微异常的本质并精确定位特定的微观病理。DMRI的进展包括开发多层成像方法以能够测量完整的3D扩散函数(传播子)，以及在临床扫描仪上实现最近开发的双脉冲磁场梯度(Double-PFG)序列。这些技术将增加扫描时间，但将提供关于组织微观结构的更具体信息，增加对大脑变化和异常的敏感性。为了使双PFG和多壳层测量在临床上都可行，我们建议使用压缩感知，这是一种先进的采样和重建策略，允许重建图像数据，其数据点比传统要求的要少得多。我们将开发新的定量分析方法，特别关注分析由双PFG序列产生的独特数据。这种类型的数据尚未在临床研究中进行调查。最后，我们将使用所提出的方案对精神分裂症患者和正常对照组进行扫描，并应用分析方法来研究组内差异。我们希望在这个项目成功完成后，我们将开发出一种临床上可行的dMRI范例，包括扫描和分析管道，这将有助于识别和量化病理导致的扩散的细微变化，这是目前的技术无法检测到的。 公共卫生相关性：总体目标是使用体内磁共振扩散成像(DMRI)来研究精神分裂症(SZ)的脑白质(WM)病理。DMRI的拟议进展包括开发多层成像方法以实现全扩散功能的测量，以及在临床扫描仪上实现最近开发的双脉冲磁场梯度(Double-PFG)序列。我们将使用建议的方案扫描精神分裂症患者和正常对照组，并应用分析方法检测SZ白质中的细胞变化。

DESCRIPTION (provided by applicant): This application is a competitive renewal of an R01 completing its first cycle. The overall goal is to use in vivo magnetic resonance diffusion imaging (dMRI) to study white matter (WM) pathology in schizophrenia (SZ). Measurement of microstructural WM pathology has the potential to have a huge impact on new SZ treatment strategies (anti-inflammatory drugs, drugs promoting cell regeneration, myelin protective medication, etc.) The previous project cycle was focused on diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) models, and established that there are subtle abnormalities in the WM in SZ. In this new proposal we plan to develop more sensitive probes of tissue microstructure using advanced dMRI scanning and analysis techniques, to help explore the nature of the subtle abnormalities and pinpoint specific micro- pathology. The proposed advances in dMRI include development of methods for multiple-shell imaging to en- able measurement of the full 3D diffusion function (the propagator), and implementation of the recently developed double pulsed field gradient (double-PFG) sequence on a clinical scanner. These technologies will in- crease the scan time but will provide more specific information about tissue microstructure, increasing the sensitivity to brain changes and abnormalities. To make both double-PFG and multiple-shell measurements feasi- ble in clinical time, we propose to employ compressed sensing, an advanced sampling and reconstruction strategy that allows reconstruction of the image data with considerably fewer data points than are traditionally required. We will develop novel quantitative analysis methods, with special focus on analysis of the unique data produced by the double-PFG sequence. This type of data has not yet been investigated in clinical studies. Finally we will scan patients with schizophrenia and normal controls with the proposed protocols and apply the analysis methods to study group differences. We expect that upon successful completion of this project, we will have developed a clinically feasible dMRI paradigm including scanning and analysis pipelines that will help identify and quantify subtle changes in diffusion induced by pathology, which cannot be detected with current technology. PUBLIC HEALTH RELEVANCE: The overall goal is to use in vivo magnetic resonance diffusion imaging (dMRI) to study white matter (WM) pathology in schizophrenia (SZ). The proposed advances in dMRI include development of methods for multiple- shell imaging to enable measurement of the full diffusion function, and implementation of the recently developed double pulsed field gradient (double-PFG) sequence on a clinical scanner. We will scan patients with schizophrenia and normal controls with the proposed protocols and apply the analysis methods to detect cellular alterations in the WM in SZ.