Multiband ASL for Alzheimer's Disease

项目总结/摘要 阿尔茨海默病（AD）是痴呆症的最常见原因，具有巨大的医疗负担。 临床前疾病的鉴定对于治疗的发展是至关重要的，因为显著的神经元死亡已经 在症状出现时已经发生了动脉自旋标记（ASL）灌注MRI是一种有吸引力的 通过利用磁标记的动脉血液水作为测量痴呆中灌注的方法 内源性示踪剂我们和其他人已经将ASL应用于研究AD和轻度认知障碍（MCI）。 后扣带回颞顶联合皮质脑灌注不足的特征性模式 在AD患者中，使用ASL检测了大脑皮质（PCC）、楔前叶和额叶皮质，在较小程度上， MCI人群。然而，使ASL成为研究AD的有效工具仍然存在一些挑战 和其他神经退行性疾病，包括：1）现有的ASL技术通常具有粗糙的空间分布， 分辨率约为4x 4x 4 mm 3，难以分解结构和功能组件， 由于部分容积效应引起的神经退行性作用; 2）建议实施伪- 采用分段3D采集的连续ASL（pCASL）易受（分段间）头部运动的影响， 经常出现在老年人群中;以及3）分段3D采集的持续时间相对较长， 允许单次标记后延迟（PLD）扫描，这易受动脉传输中年龄依赖性变化的影响 时间，影响灌注定量的准确性。父R 01项目的目标（EB 028297“多波段 ASL for Neurodevelopment Study”）旨在开发和评估尖端的多波段（MB）pCASL方案 能够提供各向同性2 mm或更高的高空间分辨率、对头部运动的抵抗力和多 延迟功能，用于儿科人群的精确灌注定量。在这个项目中，我们将 尖端的高分辨率2D和3D MB pCASL技术和深度学习（DL）去噪算法， 3组轻度AD、遗忘型MCI和年龄匹配的对照组，并与 标准pCASL方法。我们假设，开发的MB pCASL协议和DL算法更多 检测轻度AD、MCI和对照之间灌注差异的灵敏度高于标准pCASL技术 科目该项目的成功完成将导致强大的高分辨率多延迟MB pCASL 方案与相关的DL去噪算法，其可以用作AD和MCI的生物标志物。

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) is the most common cause of dementia with enormous healthcare burden. Identification of preclinical disease is critical for the development of therapy, as significant neuronal death has already occurred by the time of symptom onset. Arterial spin labeled (ASL) perfusion MRI is an appealing approach for measuring perfusion in dementia by utilizing magnetically labeled arterial blood water as an endogenous tracer. We and others have applied ASL to study AD and mild cognitive impairment (MCI). Characteristic patterns of cerebral hypoperfusion in temporoparietal association cortices, posterior cingulate cortex (PCC), precuneus and frontal cortex were detected using ASL in AD patients, and to a lesser extent, in MCI populations. However, there remain several challenges for making ASL an impactful tool in studying AD and other neurodegenerative disorders, including: 1) Existing ASL techniques generally have a coarse spatial resolution of ~4x4x4mm3, making it difficult to decompose structural and functional components of neurodegenerative effects due to partial volume effects; 2) The recommended implementation of pseudo- continuous ASL (pCASL) with segmented 3D acquisition is susceptible to (inter-segment) head motion that is frequently present in aged populations; and 3) The relatively long duration of segmented 3D acquisition generally allows a single post-labeling delay (PLD) scan, which is susceptible to age dependent variations in arterial transit time, affecting the accuracy of perfusion quantification. The goal of the parent R01 project (EB028297 “Multiband ASL for Neurodevelopment Study”) was to develop and evaluate cutting-edge multiband (MB) pCASL protocols that are able to offer a high spatial resolution of isotropic 2mm or higher, resistance to head motion and multi- delay capability for accurate perfusion quantification in pediatric populations. During this project, we will apply cutting edge high-resolution 2D and 3D MB pCASL techniques and deep-learning (DL) denoising algorithms in 3 groups of mild AD, amnestic MCI and age matched control subjects, and compare the results with those by standard pCASL methods. We hypothesize that the developed MB pCASL protocols and DL algorithms are more sensitive than standard pCASL techniques for detecting perfusion differences between mild AD, MCI and control subjects. The successful completion of this project will lead to robust high resolution multi-delay MB pCASL protocols with associated DL denoising algorithms which may serve as biomarkers for AD and MCI.