Novel Diffusion MRI in Early Psychosis

摘要 我们的目标是提供新的，临床上可行的，精确的弥散磁共振成像（dMRI）技术， 用于研究早期精神病体内人脑细胞微观结构的方法。精神病 订单是毁灭性的大脑疾病，包括一系列症状，如妄想，幻觉， 思维障碍更好地了解精神病的病因可以改善诊断， 治疗dMRI是一种非侵入性的成像方法，它可以识别出大脑中独特的微结构异常， 精神病然而，由于许多病理过程已被提出在精神病中共存，因此存在一种 需要从dMRI获得更具体的测量。 当前最先进的dMRI使用称为“DMRI”的技术沿单个方向沿着对扩散进行编码（测量）。 单扩散编码我们提出了q空间轨迹成像（QTI），这是一种新的dMRI方法， 在采集过程中改变测量方向，以更好地表征水的真实复杂性 分子运动我们提出的新QTI序列允许测量微观结构特性 用今天的扫描方法是看不见的。这些微观结构特性 在数学上表示为尺寸（CMD）、形状（Cµ）和方向（Cc）的变化， 从代表不同神经元组织微环境的混合物的模型，例如神经突、细胞 结构域和细胞外空间。 为了实现我们的目标，我们提出以下三个目标。在目标1中，我们将建立实验基础 新的dMRI。我们将研究QTI方法，以更好地表征重要的病理特征 精神病的预期。我们将扩展QTI框架，使微观结构模型和属性， 明确考虑到限制，非高斯和时间依赖性扩散。这一成功的终点 aim将为提取与精神病相关的新的微观结构特性提供措施和模型 在QTI在目标2中，我们将开发新的dMRI序列和标准。我们建议发展稳健和 快速QTI脉冲序列和扫描协议，以DICOM格式表示采集参数。的 这一目标的成功终点将是新颖、稳健和快速的采集（15分钟以下），使QTI能够 临床研究。在目标3中，我们建议研究24例早期精神病患者的基于QTI的微结构测量。 10名患者和24名匹配的对照，以解开精神病中共存的病理，如神经退行性变， 和神经炎症过程。 我们预计，在成功完成拟议项目后，我们将开发出新型dMRI， 为研究体内人脑的细胞微观结构提供了更高的灵敏度和特异性。

Abstract Our goal is to provide novel, clinically feasible, and precise diffusion magnetic resonance imaging (dMRI) tech- nologies for investigation of the in-vivo human brain's cellular microstructure in early psychosis. Psychotic dis- orders are devastating brain diseases that include a range of symptoms such as delusions, hallucinations, and thought disorder. A better understanding of the etiology of psychosis can lead to improved diagnosis and treatment. dMRI is a noninvasive imaging method that has identified unique microstructural abnormalities in psychosis. However, as many pathological processes have been proposed to co-exist in psychosis, there is a need for more specific measures derived from dMRI. Current state-of-the-art dMRI encodes (measures) diffusion along a single direction using a technique called single diffusion encoding. We propose q-space trajectory imaging (QTI), a new dMRI method that dynamically changes the measurement orientation during acquisition to better characterize the true complexity of water molecule motion. The novel QTI sequences that we propose allow measurement of microstructural properties of the in-vivo human brain that are invisible using today's scanning methods. These microstructural properties are mathematically expressed in terms of variability in size (CMD), shape (Cµ), and orientation (Cc), extracted from a model representing a mixture of distinct neuronal tissue microenvironments, such as neurites, cellular domains and extracellular spaces. To achieve our goals we propose the following three aims. In Aim 1, we will develop experimental foundations for novel dMRI. We will investigate QTI methodologies to better characterize important pathological features expected in psychosis. We will extend the QTI framework to enable microstructural models and properties that explicitly account for restricted, non-Gaussian, and time-dependent diffusion. The successful endpoint of this aim will provide measures and models for the extraction of new microstructural properties related to psychosis from QTI. In Aim 2, we will develop novel dMRI sequences and standards. We propose to develop robust and fast QTI pulse sequences and scan protocols, with representation of the acquisition parameters in DICOM. The successful endpoint of this aim will be novel, robust, and fast acquisitions (under 15 minutes), enabling QTI for clinical studies. In Aim 3, we propose to study QTI-based microstructure measures in 24 early psychosis pa- tients and 24 matched controls to disentangle pathologies that co-exist in psychosis, such as neurodegenera- tive and neuroinflammatory processes. We expect that upon successful completion of the proposed project, we will have developed novel dMRI to provide increased sensitivity and specificity for the study of the in-vivo human brain's cellular microstructure.