Controlling Quality and Capturing Uncertainty in Advanced Diffusion Weighted MRI

描述(申请人提供)：扩散加权磁共振成像(DW-MRI)为同时研究局部微体系结构和全球结构连通性提供了前所未有的机会。然而，在弥散张量成像(DTI)首次提出近20年后，DW-MRI在复杂组织区域(如交叉纤维)的解释仍然受到基础理论挑战的困扰。使用先进的DW-MRI方法了解这些复杂区域对于定量评估大脑结构组织、诊断连接异常和开发有用的生物标志物至关重要。虽然已经提出了许多潜在的采购和分析技术，但迄今为止，还没有系统地描述采购设计和质量对先进技术的影响。这项工作的激励假设是，在给定实际图像采集考虑因素(例如，可行的扫描时间、硬件、患者运动倾向)的情况下，不同的先进DW-MRI方法适合不同的成像环境。研究人员在考虑涉及高级DW-MRI的研究时面临两个关键问题：(1)可能的预期性能(特异性/敏感度)是什么 高级DW-MRI分析在特定的成像场景下？“和(2)如何在特定的DW-MRI分析场景下优化成像场景以达到目标性能水平？”本项目的总体目标是解决这些长期存在的重要问题。我们将通过一系列三个实验来评估激励假说：“首先，我们将进行迄今为止最广泛的体模研究，以绘制高级DW-MRI指标的经验敏感性和特异性图。这项研究将产生已知物理纤维结构的扫描-重新扫描数据。其次，我们将进行迄今为止最广泛的扫描-重新扫描研究，以绘制先进的DW-MRI指标在体内的重复性。这项研究将生成所有三大扫描供应商的扫描-重新扫描数据，这些志愿者的神经学正常对照志愿者的年龄和性别分层。第三，我们将与正在进行的临床研究合作，生成一个扫描-重新扫描验证数据的大型数据库。这项研究将能够绘制正常的受试者间差异图，导致建立先进的DW-MRI测量的标准化数据库，并能够进行单一受试者推断。总而言之，这些努力将(1)在噪声和采样策略的背景下，为从先进的DW-MRI获得的生物标记物的生物物理解释提供量化基础；(2)为在扫描时间和硬件限制下优化方案提供坚实的理论和经验基础。数据、分析软件和可视化工具将免费提供，以促进持续改进和创新。这些努力将推动量化 探索基于先进的DW-MRI的生物标记物，并最终改善患者护理。

DESCRIPTION (provided by applicant): Diffusion weighted magnetic resonance imaging (DW-MRI) has opened unprecedented opportunities to simultaneously study local microarchitecture and global structural connectivity. Yet, nearly two decades after the initial presentation of diffusion tensor imaging (DTI), DW-MRI remains plagued by basic theoretical challenges to its interpretation in regions of complex tissues (e.g., crossing fibers). Understanding these complex regions with advanced DW-MRI methods is critical to quantitative assessment of the brain architectural organization, diagnosing connectivity abnormalities, and developing useful biomarkers. Although numerous potential acquisition and analysis techniques have been proposed, to date, there has not been a systematic characterization of the impacts of acquisition design and quality across advanced techniques. The motivating hypothesis of this work is that different advanced DW-MRI methods are appropriate for different imaging contexts given practical image acquisition considerations (e.g., feasible scan time, hardware, propensity for patient motion). Investigators considering studies involving advanced DW-MRI are faced with two critical questions: (1) "What is the expected performance (specificity/sensitivity) of possible advanced DW-MRI analyses given a particular imaging scenario?" and (2) "How can an imaging scenario be optimized to achieve target level of performance given a particular DW-MRI analysis scenario?" The overall goal of this project is resolve these important long-standing questions. We will evaluate the motivating hypothesis through a series of three experiments: " First, we will perform the most extensive phantom study to date to map the empirical sensitivity and specificity of advanced DW-MRI metrics. This study will generate scan-rescan data of known physical fiber structures. " Second, we will perform the most extensive scan-rescan study to date to map the in vivo reproducibility of advanced DW-MRI metrics. This study will generate scan-rescan data across all three major scan vendors with neurologically normal control volunteers who are age and gender stratified. " Third, we will collaborate with on-going clinical research studies to generate a large database of scan-rescan validation data. This study will enable mapping of normal inter-subject variance, lead to the construction of a normative database of advanced DW-MRI measures, and enable single-subject inference. Together, these efforts will (1) provide a quantitative basis for biophysical interpretation of biomarkers derived from advanced DW-MRI in the context of noise and sampling strategies and (2) provide a solid theoretical and empirical basis for optimization of protocols within scan-time and hardware constraints. The data, analysis software, and visualization tools will be made freely available to facilitate continued improvement and innovation. These efforts will drive quantitative exploration for biomarkers based on advanced DW-MRI and, eventually, improve patient care.