Developing advanced diffusion MRI for early detection of Alzheimer's disease

项目摘要/摘要 阿尔茨海默病(AD)和相关痴呆症是中国最常见的神经退行性疾病之一 人口老龄化，仅在美国每年就有超过1/10的65岁及以上人口受到影响。 由于阿尔茨海默病是一种缓慢而复杂的进行性脑部疾病，在发病前及早识别大脑的变化 掌握临床症状是减少脑组织损伤、提高临床疗效的关键 干预措施。 弥散磁共振成像(MRI)是一种有前途的早期发现AD的工具，因为它具有 非侵入性，广泛的可用性，以及对细微的大脑微结构变化的敏感性。不幸的是，目前 扩散磁共振成像技术的不足有几个原因，包括(1)空间分辨率不足以 准确描绘内侧颞叶(MTL)重要但精细的白质通路，这是一个关键的 阿尔茨海默病早期传播的区域；以及(2)缺乏特异性来揭示支持AD的脑微结构 早期神经元损伤和功能障碍的变化。本方案的创新之处主要在于联合使用 信噪比高效的高分辨率扩散捕获和高级扩散编码策略，以有效地 解决当前弥散磁共振成像方法的准确性和特异性限制。具体地说，这个项目将(1) 开发高分辨率MRI协议，以更准确地分割白质和灰质区域 首先受到AD传播的影响并在其中发挥关键作用；(2)开发高级扩散编码波形 以更敏感和特异地表征AD早期微妙的脑微结构变化； (3)利用现有AD分子生物标记物，严格评价新的扩散生物标记物的疗效 用于AD的早期检测。 这一建议的结果将为研究AD的纵向进展奠定基础， 阐明AD的潜在发病机制，并评估预防和/或减缓AD的新干预策略 减少AD的发病和/或进展。应聘者在核磁共振方面有很强的背景和广泛的培训 物理学、工程学、图像处理和脑成像。再加上认知神经科学方面的额外训练， 生物统计学和多模式神经成像提供的这个程序，他将作为一个独立的装备良好 研究人员专注于(1)开发以磁共振为重点的先进神经成像技术；以及(2) 使用多模式工具集来解决基础神经科学研究中的基本问题 神经退行性疾病研究。

Project Summary / Abstract Alzheimer’s disease (AD) and related dementia are one of the most prevalent neurodegenerative disorders in the aging population, affecting more than 1 in 10 people aged 65 and older each year in the United States alone. Since AD is a slow and complex progressive brain disease, early identification of brain changes before the onset of clinical symptoms is critical for minimizing brain tissue damage and improving the effectiveness of clinical interventions. Diffusion magnetic resonance imaging (MRI) is a promising tool for the early detection of AD because of its non-invasiveness, wide availability, and sensitivity to subtle brain microstructural changes. Unfortunately, current diffusion MRI techniques can be inadequate for several reasons, including (1) insufficient spatial resolution to accurately delineate important but fine-scale white matter pathways in the medial temporal lobe (MTL), a critical region in the early propagation of AD; and (2) a lack of specificity to reveal the underpinning brain microstructural changes from early neuronal injury and dysfunction. The innovation of this proposal mainly lies in the joint use of SNR-efficient high-resolution diffusion acquisition and advanced diffusion encoding strategies to effectively address the accuracy and specificity limitations of current diffusion MRI methods. Specifically, this project will (1) develop a high-resolution MRI protocol for more accurate segmentation of white and gray matter regions that are first affected by and play critical roles in AD propagation; (2) develop advanced diffusion encoding waveforms for more sensitive and specific characterization of subtle brain microstructural changes at the early stage of AD; and (3) use existing AD molecular biomarkers to rigorously evaluate the efficacy of the new diffusion biomarkers for early AD detection. The outcomes of this proposal will lay the foundation for studying the longitudinal AD progression, elucidating the underlying AD pathogenesis, and evaluating new intervention strategies to prevent and/or slow down AD onset and/or progression. The candidate has a strong background and extensive training in MRI physics, engineering, image processing, and brain imaging. With the additional training in cognitive neuroscience, biostatistics, and multimodal neuroimaging provided by this program, he will be well equipped as an independent researcher focusing on (1) developing advanced neuroimaging techniques with a strong focus on MRI; and (2) employing a multimodal toolset to address fundamental questions in basic neuroscience research and neurodegenerative disease studies.