7T MRI as a potential tool for detection of pathology in Alzheimer's disease

项目概要/摘要 β 淀粉样蛋白 (Aβ) 是称为淀粉样前体蛋白的较大蛋白质的一小部分。它累积在 阶段为微小的淀粉样蛋白斑块，这被认为是受阿尔茨海默病影响的大脑的标志 疾病（AD）。正电子发射断层扫描 (PET) 是一种体内检测 Aβ 斑块的成熟技术。 一些临床前和尸检数据报告了 Aβ 斑块附近氧化还原活性铁的积累。 已经尝试使用各种技术对 Aβ 斑块进行磁共振成像 (MRI)，特别是 与敏感性对比。迄今为止，MRI 中 Aβ 斑块的非侵入性检测能力已在很大程度上得到了证实。 归因于伴随 Aβ 斑块的铁沉积。据认为，磁化率缩短 顺磁性铁的作用是斑块与周围组织之间对比度的主要来源。我们 假设铁相关 Aβ 的聚集会增加电子密度并引起显着的 局部磁敏感值的变化。由于在超高场 (UHF) 强度下具有更高的敏感性，感应 铁磁化率足够大，可以产生相对于周围正常组织的对比度 通过 7 特斯拉 (7T) MRI 的定量磁化率技术可视化。 该提案的目标是提出一个用于病理分析的替代平台 得益于超高场 (7T) MR 神经影像，AD 患者的生物标志物。的发展 7T 磁化率 MRI 的专用序列将使 AD 中的比较和微观结构数据成为可能 患者以前所未有的决心；反过来，这将提供对体内的更深入的了解 AD 的病理生理学，使我们能够潜在地识别一组基于易感性的疾病标志物 病理学。具体来说，我们希望我们的综合方法能够帮助我们验证 UHF MRI 作为一种独特的工具 改善 AD 诊断和预后测量。我们的中心假设是 UHF MRI 提供了 与 AD 相关的大脑变化的独特而强大的测量方法，并且可以与 现有的神经影像工具可以实现疾病后果的前所未有的可视化 病理学。 该职业发展项目还包括旨在完善和解决职业发展差距的培训计划。 申请人的技术和科学知识和经验，发展他的研究职业技能，暴露 他进入了神经影像学和神经科学界，并为他的职业生涯奠定了基础 独立科学家。培训计划包括：神经系统疾病、临床 神经科学、研究资助申请和预算管理；介绍他在技术方面的工作 MRI 和神经科学会议；提供正式的课堂讲座和小组教学 会议；研究志愿者的指导；组织研究研讨会；和实践培训 在研究项目进行期间。

Project Summary/Abstract Amyloid-beta (Aβ) is a small piece of a larger protein called amyloid precursor protein. It accumulates in stages into microscopic amyloid plaques that are considered a hallmark of a brain affected by Alzheimer’s disease (AD). Positron emission tomography (PET) is an established technique to detect Aβ plaques in vivo. Some preclinical and postmortem data report an accumulation of redox-active iron near Aβ plaques. magnetic resonance imaging (MRI) of Aβ plaques has been attempted using various techniques, notably with susceptibility contrast. The non-invasive detectability of Aβ plaques in MRI has so far been largely attributed to iron deposition accompanying Aβ plaques. It is believed that the susceptibility shortening effects of paramagnetic iron are the primary source of contrast between plaques and surrounding tissue. We hypothesized that aggregations of iron associated Aβ would increase electron density and induce notable changes in local susceptibility value. Due to higher susceptibility at ultra-high field (UHF) strengths, induced iron susceptibility is large enough to generate contrast relative to surrounding normal tissues that can be visualized by quantitative susceptibility techniques at 7 Tesla (7T) MRI. The goal of this proposal is to bring forward an alternative platform for analysis of pathologic biomarkers in AD patients, thanks to ultrahigh field (7T) MR neuroimaging. The development of specialized sequences for 7T susceptibility MRI will enable the comparison and microstructural data in AD patients at an unprecedented resolution; this, in turn, will provide a deeper understanding of the in vivo pathophysiology of AD and allow us to potentially identify a set of susceptibility-based markers of disease pathology. Specifically, we expect our integrated approach to help us validate UHF MRI as a unique tool to improve AD diagnosis and prognostic measurements. Our central hypothesis is that UHF MRI provides a unique and powerful measure of changes associated with AD in the brain, and may be integrated with existing neuroimaging tools to achieve unprecedented visualization of the consequences of disease pathology. This career development project also includes a training plan designed to refine and address gaps in the applicant’s technical and scientific knowledge and experience, develop his research career skills, expose him to the neuroimaging and neuroscience communities, and lay the groundwork for his career as an independent scientist. The training plan encompasses: coursework in neurological disorders, clinical neuroscience, research grant applications, and budget management; presentation of his work at technical MRI and neuroscience conferences; delivery of formal classroom lectures and small-group teaching sessions; mentorship of research volunteers; organizing a research symposium; and hands-on training during the conduct of the research project.