Diffusion MRI Model Parameter Estimation to Study Brain Microstructure as it Relates to Cognitive Status in Mild Traumatic Brain Injury

项目摘要 轻度创伤性脑损伤（MTBI）是一个主要的公共卫生问题，在美国每年的发病率超过2 万我们建议使用一个创新的范例在双组分扩散MRI模型参数 估计研究动态纵向微观结构的变化，发生后MTBI和调查 白色物质损伤、皮质体积损失和认知结果之间的联系。我们的初步研究结果 提出了轴突完整性基于扩散的生物物理参数，包括轴突内扩散率（Da）和 轴突水分数（f）可以检测MTBI中的微结构变化，并提供更多的生物病理学相关性。 与传统的经验性扩散张量成像（DTI）测量相比，我们将雇用一名 旋转不变的形式主义和参数估计方案的所谓的“标准模型”， 在白色物质中的扩散，统一了之前对多室白色物质建模的尝试 在过去的十年中，现在是广泛接受的大脑中扩散的多室建模的基准。我们 将进一步结合球面张量编码（STE）和球面峰度（SK），以提高 轴突特异性微结构参数的中心，这个项目，并使用优化和临床可行的 这个翻译项目的协议。预计拟议的工作将弥合宏观和微观之间的差距。 以及与损伤后认知状态相关的微结构改变，揭示了动态结构变化， 损伤后发生的变化，并指出与认知结果最相关的成像生物标志物。通过 集中在认知结果，我们将解决预测MTBI结果的主要障碍之一 这是临床状态的异质性。这项工作的结果预计将是显着的，从两个 科学和临床观点，1）以有效的方式推进损伤的基础知识，2） 发现与MTBI中的认知状态相关的生物药理学上有意义的成像生物标志物，以及3） 机械地连接微观结构和宏观结构的大脑改变，在三个各自的具体目标。 这将提供一种对认知领域特定的损伤和恢复进行定量跟踪的手段， 和跟踪有针对性的认知治疗策略的疗效，如认知康复， MTBI患者的综合行为健康治疗。

PROJECT SUMMARY Mild Traumatic Brain Injury (MTBI) is a major public health problem with U.S. annual incidence of over 2 million. We propose to use an innovative paradigm in bicompartment diffusion MRI model parameter estimation to study the dynamic longitudinal microstructural changes that occur after MTBI and to investigate the link between white matter injury, cortical volume loss and cognitive outcome. Our preliminary findings suggest diffusion-based biophysical parameters of axon integrity including intra-axonal diffusivity (Da) and axonal water fraction (f) can detect microstructure changes in MTBI and provide more biophysically relevant information compared with traditional, empirical measures of Diffusion Tensor Imaging (DTI). We will employ a rotationally invariant formalism and parameter estimation scheme for the so-called “Standard Model” of diffusion in white matter which unifies previous attempts of multi-compartment white matter modeling over the past decade, now a widely accepted benchmark for multi-compartment modeling of diffusion in the brain. We will further incorporate spherical tensor encoding (STE) and spherical kurtosis (SK) to increase the precision in axon-specific microstructure parameters central to this project and use an optimized and clinically feasible protocol for this translational project. The proposed work is expected to bridge the gap between macroscopic and microstructural alterations relevant to cognitive status after injury, revealing the dynamic structural changes occurring after injury and pointing to imaging biomarkers most relevant to cognitive outcome. By concentrating on cognitive outcome, we will address one of the main barriers to predicting outcome in MTBI which is heterogeneity of clinical status. The results of this work are expected to be significant from both scientific and clinical perspectives by 1) advancing basic knowledge of injury in an impactful way, 2) discovering biophysically meaningful imaging biomarkers relevant to cognitive status in MTBI, and 3) mechanistically linking microstructural and macrostructural brain alterations, in three respective specific aims. This will provide a means toward quantitative tracking of injury and recovery specific to the cognitive domain, and tracking of efficacy of targeted cognitive therapeutic strategies such as cognitive rehabilitation and integrated behavioral health treatment in patients with MTBI.