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

项目总结/摘要 阿尔茨海默氏病（AD）和相关痴呆是阿尔茨海默氏病中最普遍的神经退行性疾病之一。 人口老龄化，仅在美国，每年就有超过十分之一的65岁及以上的人受到影响。 由于AD是一种缓慢而复杂的进行性脑部疾病， 对于最大限度地减少脑组织损伤和提高临床治疗的有效性至关重要。 干预措施。 扩散磁共振成像（MRI）是一种很有前途的工具，早期发现AD，因为它 非侵入性、广泛的可用性和对细微的脑微结构变化的敏感性。不幸的是，目前 扩散MRI技术可能由于几个原因而不充分，包括（1）空间分辨率不足， 准确描绘重要但精细的内侧颞叶（MTL）白色物质通路， AD早期传播的区域;（2）缺乏特异性来揭示基础脑微结构 早期神经元损伤和功能障碍的变化。这一建议的创新之处主要在于联合使用 有效的SNR高分辨率扩散采集和先进的扩散编码策略， 解决了当前弥散MRI方法的准确性和特异性限制。具体而言，本项目将（1） 开发一种高分辨率MRI协议，用于更准确地分割白色和灰质区域， 首先受到AD传播的影响并在AD传播中起关键作用;（2）开发高级扩散编码波形 更敏感和特异地表征AD早期脑微结构的细微变化; 以及（3）使用现有的AD分子生物标志物来严格评估新扩散生物标志物的功效 早期AD检测 本研究的结果将为研究AD的纵向进展奠定基础， 阐明潜在的AD发病机制，并评估新的干预策略，以预防和/或减缓 降低AD发作和/或进展。候选人在MRI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。通过认知神经科学的额外培训， 生物统计学和多模式神经成像提供了这个程序，他将配备良好的独立 研究人员专注于（1）开发先进的神经成像技术，重点关注MRI;和（2） 采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.