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

7T MRI 作为检测阿尔茨海默病病理的潜在工具

• 批准号: 10349883
• 负责人: Akbar Alipour
• 金额: $ 10.69万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10349883
• 关键词: Address; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease patient; Amyloid; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Anatomy; Applications Grants; Autopsy; Biological; Biological Markers; Brain; Brain region; Budgets; Clinical; Communities; Contracts; Control Groups; Data; Data Reporting; Deposition; Detection; Development; Diagnosis; Disease; Disease Marker; Disease Progression; Early Diagnosis; Educational process of instructing; Exposure to; Functional disorder; Goals; Homeostasis; Human; Image; Imaging Techniques; Impairment; Individual; Investigation; Iron; Knowledge; Magnetic Resonance Imaging; Magnetism; Measurement; Measures; Mentorship; Methods; Microscopic; Microscopy; Nerve Degeneration; Neurofibrillary Tangles; Neurosciences; Neurosciences Research; Noise; Normal tissue morphology; Onset of illness; Outcome; Oxidation-Reduction; Pathologic; Pathology; Patients; Pattern; Performance; Play; Positron-Emission Tomography; Predisposition; Production; Professional Competence; Property; Proteins; Protocols documentation; Radiation; Research; Research Project Grants; Resolution; Role; Scanning; Scientist; Senile Plaques; Signal Transduction; Source; Techniques; Testing; Time; Tissues; Training; Variant; Visualization; Work; abeta accumulation; base; career; career development; clinical diagnosis; cohort; design; diagnostic tool; disease prognosis; disease prognostic; electron density; experience; healthy volunteer; improved; in vivo; insight; interest; lectures; magnetic field; nervous system disorder; neuroimaging; neuropathology; novel; pre-clinical; radio frequency; radiotracer; recruit; sex; symposium; tissue mapping; tool; ultra high resolution; volunteer

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.

项目摘要/摘要 淀粉样蛋白β（Aβ）是一小部分，称为淀粉样蛋白前体蛋白。它积累了 分为微观淀粉样蛋白斑块，被认为是受阿尔茨海默氏症影响的大脑的标志 疾病（AD）。正电子发射断层扫描（PET）是一种在体内检测Aβ斑块的既定技术。 一些临床前和验尸数据报告了Aβ斑块附近的氧化还原活性铁的积累。 Aβ斑块的磁共振成像（MRI）已尝试使用各种技术，尤其是 具有易感性对比。到目前为止 归因于铁沉积参与Aβ斑块。人们认为易感性缩短 顺磁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引起显着的 局部易感性值的变化。由于超高场（UHF）强度较高的敏感性，引起了 铁敏感性足够大，可以产生相对于周围正常组织的对比度 通过7 Tesla（7T）MRI的定量敏感性技术可视化。 该提案的目的是提出一个替代平台来分析病理学 AD患者的生物标志物，感谢您对超高领域（7T）神经影像学先生。发展的发展 7T敏感性MRI的专门序列将使AD中的比较和微结构数据 以空前分辨率的患者；反过来，这将提供对体内的更深入的理解 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记 病理学。特别是，我们希望我们的集成方法可以帮助我们验证UHF MRI作为独特的工具 改善AD诊断和预后测量。我们的中心假设是UHF MRI提供了 对与大脑中AD相关的变化的独特而有力的测量，可以与 现有的神经影像学工具以实现疾病后果的前所未有的可视化 病理。 该职业发展项目还包括一个旨在完善和解决差距的培训计划 申请人的技术和科学知识和经验，发展他的研究职业技能，展现 他对神经影像学和神经科学社区，并为他的职业生涯奠定了基础 独立科学家。培训计划包括：神经系统疾病的课程工作，临床 神经科学，研究赠款应用和预算管理；他在技术上的工作介绍 MRI和神经科学会议；提供正式的教室讲座和小组教学 会议；研究志愿者的指导；组织研究研讨会；和动手培训 在研究项目的过程中。