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

项目摘要/摘要 淀粉样β蛋白(Aβ)是一种较大的蛋白质的一小部分，称为淀粉样前体蛋白。它累积在 进展为微小的淀粉样斑块，被认为是阿尔茨海默病患者大脑的标志 疾病(AD)。正电子发射断层扫描是一种在活体内检测Aβ斑块的成熟技术。 一些临床前和尸检数据报告说，Aβ斑块附近积累了氧化还原活性铁。 已经尝试使用各种技术对β斑块进行磁共振成像，特别是 敏感度对比。到目前为止，β斑块在磁共振成像中的非侵入性检测能力很大程度上 归因于伴随Aβ斑块的铁沉积。据认为，磁化率的缩短 顺磁性铁的影响是斑块和周围组织之间对比的主要来源。我们 假设铁结合的Aβ的聚集会增加电子密度并引起显著的 局部敏感值的变化。由于在超高场(UHF)强度下具有更高的磁化率， 铁的敏感性足够大，足以产生相对于周围正常组织的对比度 在7特斯拉(7T)磁共振成像上用定量敏感性技术进行可视化。 这项建议的目的是为病理分析提供一个替代平台 阿尔茨海默病患者的生物标志物，这要归功于超高场(7T)磁共振神经成像。的发展。 7T敏感性MRI的特殊序列将使AD的比较和显微结构数据成为可能 患者以前所未有的分辨率；这反过来将提供对体内 AD的病理生理学，并使我们有可能识别一组基于疾病易感性的标记 病理学。具体地说，我们希望我们的集成方法能够帮助我们验证UHF MRI作为一种独特的工具 改善AD的诊断和预后测量。我们的中心假设是超高频核磁共振提供了 独特而强大的测量大脑中与AD相关的变化的方法，并可与 现有的神经成像工具可实现疾病后果的前所未有的可视化 病理学。 这一职业发展项目还包括一项培训计划，旨在完善和解决以下方面的差距 申请人的技术和科学知识和经验，发展他的研究事业技能，暴露 他进入了神经成像和神经科学界，为他的职业生涯奠定了基础 独立科学家。培训计划包括：神经性疾病的课程，临床 神经科学、研究资助申请和预算管理；在理工学院介绍他的工作 核磁共振和神经科学会议；提供正式课堂讲课和小组教学 会议；指导研究志愿者；组织一次研究专题讨论会；以及动手培训 在进行研究项目的过程中。

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.