Advancing methods for mapping short-range association fibers in the aging brain

绘制衰老大脑中短程关联纤维图谱的先进方法

• 批准号: 10480838
• 负责人: Qiyuan Tian
• 金额: $ 13.39万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-05 至 2023-02-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480838
• 关键词: Accounting; Address; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Amyloid beta-Protein; Anatomy; Area; Autopsy; Axon; Brain; Brain region; Choristoma; Clinical; Clinical Research; Cognitive; Collaborations; Complement; Connective Tissue; Coupled; Data; Dementia; Demyelinations; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Distant; Effectiveness; Elderly; Environment; Epidemic; Equilibrium; Faculty; Fiber; General Hospitals; Goals; Grant; Histologic; Hour; Human; Image; Image Analysis; Impaired cognition; Individual; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Light; Magnetic Resonance Imaging; Maps; Massachusetts; Measurement; Measures; Mediating; Mental disorders; Mentors; Mentorship; Methodology; Methods; Modeling; Molecular; Nerve Degeneration; Neurodegenerative Disorders; Neurofibrillary Tangles; Noise; Optical Coherence Tomography; Pathogenesis; Pathologic; Pathology; Positioning Attribute; Positron-Emission Tomography; Process; Property; Research; Research Personnel; Resolution; Resources; Role; Sampling; Scanning; Structure; System; Techniques; Technology; Thinness; Time; Tissues; Training; Translating; Translational Research; Translations; Validation; Work; age related; aging brain; biomedical imaging; career; career development; cognitive development; connectome; data quality; deep learning; developmental disease; early detection biomarkers; entorhinal cortex; gray matter; image processing; improved; in vivo; mental state; mild cognitive impairment; molecular marker; multidisciplinary; nervous system disorder; neuroimaging; next generation; pre-clinical; research study; skills; tau Proteins; tractography; ultra high resolution; uptake; white matter

PROJECT ABSTRACT White matter (WM) microstructural and connectional alterations are increasingly recognized as sensitive biomarkers of early pathological changes in Alzheimer’s disease (AD). Due to limitations in spatial resolution and diffusion-encoding sensitivity of conventional diffusion MRI techniques, only long-range fiber tracts in deep WM have been accurately mapped and studied in AD. Little is known about the short-range association fibers (SAFs) in superficial WM, even though they contribute to 90% WM connections and are more vulnerable to age-related degeneration than deep WM according to the retrogenesis model of AD. This proposal aims to improve the accuracy and feasibility of SAF mapping using ultra-high-resolution (1 mm isotropic or higher) and high-sensitivity diffusion MRI in AD. Specifically, the candidate will develop an optimal acquisition strategy for in vivo mapping of SAFs, leveraging knowledge learned from histological validation using ex vivo diffusion MRI and polarization- sensitive optical coherence tomography; and employ developed methods to quantitatively determine when, where and how aberrant tissue properties and connections of SAFs occur in AD and how they relate to cognitive and molecular biomarkers in individuals with concurrent MRI and PET, as well as elucidate the role of short- range cortico-cortical connections in the spread of pathological tau proteins in AD. This proposal will advance next-generation diffusion MRI tractography and microstructural imaging at 1 mm isotropic or higher resolution for mapping SAFs and fine-scale structures across the whole brain in AD, clarify the effectiveness of SAFs as biomarkers of early pathological changes in AD, and shed light into the spread of tau through axonal connections. The candidate’s long-term career goal is to become an independent investigator dedicated to developing cutting-edge neuroimaging methodology, advancing the clinical utilization of these advanced neuroimaging technologies in the diagnosis, characterization and tracking of neurodegenerative diseases, and advancing understanding of the pathological mechanisms that cause dementia. This candidate has in-depth training in state-of-the-art diffusion MRI and tractography, image processing and analysis, and deep learning. During this K award, he will work with a multi-disciplinary team of mentors and collaborators to acquire additional expertise in histological validation, brain aging and neurodegenerative diseases as well as clinical translational research, which are essential for him to implement the proposed research and lead an independent laboratory. The exceptional resources, mentorship and collaboration at the Massachusetts General Hospital Martinos Center for Biomedical Imaging and Alzheimer's Disease Research Center will provide an ideal environment for the candidate to achieve both his scientific and career development goals.

项目摘要 白质（WM）微结构和连接变化越来越被认为是敏感的 阿尔茨海默氏病早期病理变化的生物标志物（AD）。由于空间分辨率和 传统扩散MRI技术的扩散 - 编码敏感性，仅在深WM中的远距离纤维区域 在AD中精确映射并研究了。关于短距离关联纤维（SAFS）知之甚少 在浅表Wm中，即使它们贡献了90％的WM连接，并且更容易受到年龄相关的影响 根据AD的回溯模型而不是深WM的变性。该建议旨在改善 使用超高分辨率（各向同性或更高）和高敏性的SAF映射的准确性和可行性 AD中的扩散MRI。具体而言，候选人将制定用于体内映射的最佳采集策略 SAFS，利用从组织学验证中学到的知识，使用离体扩散MRI和极化 - 敏感的光学相干断层扫描；并采用开发的方法来定量确定何时 AD中SAF的何处以及如何在何处以及如何发生SAF的关系以及它们与认知的关系 以及同时MRI和PET的个体中的分子生物标志物，并阐明了短期的作用 病理tau蛋白在AD中传播的皮质皮质连接范围。该提议将进步 下一代扩散MRI拖拉术和微分辨率或更高分辨率的微结构成像 为了在AD中绘制整个大脑的SAFS和精细尺度结构，阐明SAFS的有效性为 AD早期病理变化的生物标志物，并通过轴突连接散发出tau的传播。 候选人的长期职业目标是成为致力于发展的独立调查员 尖端的神经影像学方法，推进了这些晚期神经影像学的临床利用 神经退行性疾病的诊断，表征和跟踪中的技术以及前进 了解引起痴呆的病理机制。该候选人在深入的培训 最先进的扩散MRI和拖拉机，图像处理和分析以及深度学习。在此期间 K奖，他将与多学科的导师和合作者合作，以获得更多的专业知识 在组织学验证中，大脑衰老和神经退行性疾病以及临床翻译研究， 这对于他实施拟议的研究并领导独立实验室至关重要。 马萨诸塞州总医院马蒂诺斯中心 生物医学成像和阿尔茨海默氏病研究中心将为您提供理想的环境 候选人可以实现他的科学和职业发展目标。