Velocity-Selective Arterial Spin Labeling based Perfusion Mapping for Alzheimer's disease

项目摘要 阿尔茨海默病(AD)是导致老年人群痴呆的主要原因。影像生物标志物 已经在PET上建立了各自的示踪剂，用于绘制淀粉样蛋白和tau的累积以及 神经退行性变。此外，脑血管疾病(CVD)和阿尔茨海默病(AD)之间有相当大的重叠 提示两种病理对认知功能下降的相加或协同作用。血管功能障碍也有 被认为是一个重要的生物标志物，可以更好地理解和表征这种多因素 疾病。可靠的神经退行性变和血管功能障碍的标测可能在许多 临床应用。脑血流量(CBF)是表征脑血流动力学的一个基本参数 脑血流灌注既是神经功能的替代指标，也是小血管疾病的标志。大动脉旋转 标记(ASL)灌注MRI具有不需要外源性造影剂和 没有电离辐射。在一次就诊中同时获得结构MRI和灌注MRI是 非常适合对老年受试者进行扫描。基于空间选择性的CBF图的解释 ASL方法需要谨慎的人工灌注不足，因为缓慢的血流经常发生在 年龄较大的受试者。尽管在这一领域作出了许多努力，但仍有一个尚未得到满足的迫切需要 基于ASL的标准化、可靠且经过验证的CBF映射协议，适用于跨供应商的多站点 阿尔茨海默病的神经影像研究。速度选择ASL(VSASL)派生的CBF图非常适合于 老年人群中神经退行性变和血管功能障碍的特征 忍受着缓慢流动带来的限制。我们已经实现了第一次速度选择性反演 基于VSI的VSASL在成人脑中的3D采集及其对灌注的更高敏感性 信号优于传统的ASL方法。这项拟议的工作利用了VSI的高灌流敏感性- ASL被第一份关于VSASL的指导文件以及加速购置和重建所承认 战略，并代表其第一个AD应用程序。本研究的目的是进一步优化3D VSI-ASL 加速购置和重建，然后确保其多供应商兼容性(目标1)；评估 其在会话、供应商和模式之间的重复性和有效性(目标2)；以表征VSI-ASL 认知正常(CN)受试者、MCI和AD患者不同脑区的CBF值 通过横向和纵向比较(目标3)。我们将演示优化后的3D VSI-ASL技术具有很高的重复性、有效性和敏感性，可用于检测脑血流灌注的变化和 神经退行性变，可以很容易地作为一种更实用和更具成本效益的成像生物标志物 AD和ADRD的多中心和多供应商临床研究中的神经变性和血管功能障碍。

Project Abstract Alzheimer's Disease (AD) is the leading cause of dementia in elderly population. Imaging biomarkers have been established on PET with respective tracers for mapping accumulation of amyloid and tau, as well as neurodegeneration. Furthermore, considerable overlap between cerebrovascular disease (CVD) and AD suggest additive or synergistic effects of both pathologies on cognitive decline. Vascular dysfunction has also been recognized as an important biomarker for better understanding and characterizing this multifactorial disease. Reliable mapping of neurodegeneration and vascular dysfunction could play critical roles in many clinical applications. Cerebral blood flow (CBF) is a fundamental hemodynamic parameter that characterizes brain perfusion as both a surrogate of neuro function and a marker for small vessel disease. Arterial spin labeling (ASL) perfusion MRI offers the great advantages of not requiring an exogenous contrast agent and being free of ionizing radiation. Obtaining both structural MRI and perfusion MRI in a single visit to the clinic is highly desirable for scanning the elderly subjects. Interpretation of CBF maps derived from spatially selective ASL methods need to be cautious about the artificial perfusion deficit due to the slow flow often incurred in the older subjects. Despite many efforts in this field, there remains to be an unmet and urgent need to establish a standardized, reliable, and validated ASL-based CBF mapping protocol for multi-site across-vendor neuroimaging studies for AD. Velocity-selective ASL (VSASL) derived CBF maps are ideally suited for characterization of both neurodegeneration and vascular dysfunction among the elderly population, without suffering the limitations presented by the slow flow. We have implemented the first velocity-selective inversion (VSI) based VSASL with 3D acquisition on adult brains and demonstrated its higher sensitivity to perfusion signal over conventional ASL methods. The proposed work capitalizes on the high perfusion sensitivity of VSI- ASL recognized by the first guideline paper for VSASL, as well as accelerated acquisition and reconstruction strategy, and represents its first AD application. The purpose of this study is to further optimize 3D VSI-ASL with accelerated acquisition and reconstruction, and then ensure its multi-vendor compatibility (Aim 1); to evaluate its reproducibility and validity between sessions, vendors, and modalities (Aim 2); to characterize VSI-ASL derived CBF values of various brain regions in cognitively normal (CN) subjects, and patients with MCI and AD through both cross-sectional and longitudinal comparisons (Aim 3). we will have demonstrated the optimized 3D VSI-ASL technique with high reproducibility, validity, and sensitivity to detect changes in brain perfusion and neurodegeneration, which can be readily utilized as a more practical and cost-effective imaging biomarker of neurodegeneration and vascular dysfunction for multi-center and multi-vendor clinical studies of AD and ADRD.