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）是一种称为淀粉样前体蛋白的较大蛋白质的一小部分。它积累在 淀粉样斑块被认为是大脑受阿尔茨海默氏症影响的标志 疾病（AD）。正电子发射断层扫描（PET）是检测体内Aβ斑块的成熟技术。 一些临床前和尸检数据报告了氧化还原活性铁在Aβ斑块附近的蓄积。 已尝试使用各种技术对Aβ斑块进行磁共振成像（MRI）， 对比磁化率。到目前为止，MRI中Aβ斑块的非侵入性检测能力在很大程度上 归因于伴随Aβ斑块的铁沉积。据信磁化率缩短 顺磁性铁的作用是斑块和周围组织之间对比的主要来源。我们 假设铁相关Aβ的聚集会增加电子密度并诱导显著的 局部磁化率值的变化。由于在超高场（UHF）强度下的较高磁化率， 铁敏感性足够大以产生相对于周围正常组织的对比， 在7特斯拉（7 T）MRI下通过定量磁化率技术可视化。 该提案的目标是提出一个替代平台，用于分析病理性 生物标志物在AD患者中，由于磁共振场（7 T）磁共振神经成像。的发展 7 T磁敏感性MRI的专用序列将使AD的比较和显微结构数据成为可能。 患者获得前所未有的分辨率;这反过来又将提供对体内的更深入了解 AD的病理生理学，并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，超高频MRI提供了一个 这是一种独特而强大的测量大脑中与AD相关的变化的方法， 现有的神经成像工具，以实现前所未有的可视化的疾病的后果， 病理 这一职业发展项目还包括一项培训计划，旨在完善和解决 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 他向神经成像和神经科学界，并奠定了他的职业生涯作为一个 独立科学家培训计划包括：神经系统疾病课程，临床 神经科学，研究资助申请和预算管理;介绍他在技术 MRI和神经科学会议;提供正式的课堂讲座和小组教学 研讨会;指导研究志愿者;组织研究专题讨论会;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.