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的竞争性更新。总体目标是使用在体磁共振扩散成像 （dMRI）研究精神分裂症（SZ）的白色物质（WM）病理。微结构WM病理学的测量有可能对新的SZ治疗策略（抗炎药、促进细胞再生的药物、髓鞘保护药物等）产生巨大影响。上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，并确定SZ的WM存在细微异常。在这项新提案中，我们计划使用先进的dMRI扫描和分析技术开发更灵敏的组织微观结构探针，以帮助探索细微异常的性质并查明特定的微观病理学。dMRI的拟议进展包括开发多壳层成像方法，以实现完整3D扩散函数（传播函数）的测量，以及在临床扫描仪上实施最近开发的双脉冲场梯度（双PFG）序列。这些技术将增加扫描时间，但将提供有关组织微观结构的更具体信息，提高对大脑变化和异常的敏感性。为了使双PFG和多壳测量在临床时间内可行，我们建议采用压缩感知，这是一种先进的采样和重建策略，允许用比传统所需少得多的数据点重建图像数据。我们将开发新的定量分析方法，特别关注双PFG序列产生的独特数据的分析。尚未在临床研究中对此类数据进行研究。最后，我们将扫描精神分裂症患者和正常对照组与建议的协议，并应用分析方法来研究组间差异。我们预计，在成功完成该项目后，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由病理引起的扩散中的细微变化，而这些变化是目前技术无法检测到的。 公共卫生相关性：总体目标是使用体内磁共振扩散成像（dMRI）研究精神分裂症（SZ）的白色物质（WM）病理。dMRI的拟议进展包括开发多壳成像方法，以实现全扩散功能的测量，以及在临床扫描仪上实施最近开发的双脉冲场梯度（双PFG）序列。我们将扫描精神分裂症患者和正常对照组与建议的协议，并应用分析方法来检测细胞的改变，在SZ的WM。

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.