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

扩散 MRI 模型参数估计研究脑微结构，因为它与轻度创伤性脑损伤的认知状态有关

• 批准号: 10677796
• 负责人: Sohae Chung
• 金额: $ 65.35万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677796
• 关键词: Affect; Animals; Anisotropy; Attention; Axon; Behavioral; Benchmarking; Biophysics; Brain; Brain Injuries; Cells; Clinical; Cognition; Cognitive; Complex; Confusion; Corpus Callosum; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Elements; Evolution; Fiber; Goals; Human; Image; Impaired cognition; Incidence; Injury; Investigation; Knowledge; Link; Literature; Magnetic Resonance Imaging; Measures; Mediating; Methods; Modeling; Neurobehavioral Manifestations; Outcome; Parameter Estimation; Pathology; Patient Triage; Patient-Focused Outcomes; Patients; Population; Process; Protocols documentation; Public Health; Recovery; Risk; Scheme; Short-Term Memory; Standard Model; Stretching; Structure; Symptoms; TBI Patients; Techniques; Testing; Therapeutic; Tissues; Translating; Water; Work; axon injury; behavioral health; biomechanical model; biophysical properties; clinical heterogeneity; clinically significant; cognitive function; cognitive recovery; cognitive rehabilitation; disabling symptom; experience; head impact; human model; imaging biomarker; in vivo; innovation; mild traumatic brain injury; novel; oculomotor; outcome prediction; persistent symptom; processing speed; rate of change; white matter; white matter injury

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.

项目概要 轻度创伤性脑损伤 (MTBI) 是一个重大的公共卫生问题，美国年发病率超过 2 百万。我们建议在双室扩散 MRI 模型参数中使用创新范例 估计来研究 MTBI 后发生的动态纵向微观结构变化并调查 白质损伤、皮质体积减少和认知结果之间的联系。我们的初步调查结果 建议基于扩散的轴突完整性生物物理参数，包括轴突内扩散率 (Da) 和 轴突水分数 (f) 可以检测 MTBI 中的微观结构变化并提供更多的生物物理相关性 信息与扩散张量成像（DTI）的传统经验测量相比。我们将聘请一名 所谓“标准模型”的旋转不变形式和参数估计方案 白质扩散，它统一了之前多室白质建模的尝试 过去十年，现在已成为广泛接受的大脑扩散多室建模基准。我们 将进一步结合球形张量编码（STE）和球形峰度（SK）来提高精度 轴突特异性微观结构参数是该项目的核心，并使用优化且临床可行的 该翻译项目的协议。拟议的工作预计将弥合宏观经济之间的差距 以及与损伤后认知状态相关的微观结构变化，揭示了动态结构 损伤后发生的变化并指向与认知结果最相关的成像生物标志物。经过 专注于认知结果，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。预计这项工作的结果将对双方都产生重大影响 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 认知状态相关的具有生物物理意义的成像生物标志物，以及 3) 在三个各自的具体目标中，机械地联系微观结构和宏观结构的大脑改变。 这将为定量跟踪特定于认知领域的损伤和恢复提供一种方法， 跟踪有针对性的认知治疗策略的效果，例如认知康复和 MTBI 患者的综合行为健康治疗。