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) 微观结构和连接的改变越来越被认为是敏感的 由于空间分辨率和阿尔茨海默病（AD）早期病理变化的生物标志物。 传统扩散 MRI 技术的扩散编码灵敏度，仅深部 WM 中的长距离纤维束 在 AD 中，人们对短程关联纤维（SAF）知之甚少。 在浅层 WM 中，尽管它们贡献了 90% 的 WM 连接并且更容易受到与年龄相关的影响 根据 AD 的逆发生模型，该提案旨在改善 WM 的退化。 使用超高分辨率（1 毫米各向同性或更高）和高灵敏度进行 SAF 测绘的准确性和可行性 具体来说，候选人将制定体内映射的最佳采集策略。 SAF，利用从使用离体扩散 MRI 和偏振的组织学验证中学到的知识 灵敏的光学相干断层扫描；并采用已开发的方法来定量确定何时， AD 中异常组织特性和 SAF 联系的发生地点和方式以及它们与认知的关系 和分子生物标志物在个体中同时进行 MRI 和 PET，并阐明短期的作用 该提案将推进 AD 病理性 tau 蛋白传播中的一系列皮质-皮质连接。 下一代扩散 MRI 纤维束成像和 1 毫米各向同性或更高分辨率的微观结构成像 为了绘制 AD 中整个大脑的 SAF 和精细结构，阐明 SAF 的有效性： AD 早期病理变化的生物标志物，并揭示 tau 通过轴突连接的传播。 候选人的长期职业目标是成为一名致力于开发 尖端的神经影像方法，促进这些先进神经影像的临床应用 神经退行性疾病的诊断、表征和跟踪技术，以及推进 了解导致痴呆症的病理机制。该候选人接受过深入的培训。 在此期间，我们使用最先进的扩散 MRI 和纤维束成像、图像处理和分析以及深度学习。 K 奖后，他将与由导师和合作者组成的多学科团队合作，获得更多专业知识 在组织学验证、脑衰老和神经退行性疾病以及临床转化研究中， 这对于他实施拟议的研究和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的卓越资源、指导和合作 生物医学成像和阿尔茨海默病研究中心将为研究人员提供理想的环境 候选人实现其科学和职业发展目标。