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

基于速度选择性动脉自旋标记的阿尔茨海默病灌注图

• 批准号: 10662909
• 负责人: Qin Qin
• 金额: $ 244.85万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662909
• 关键词: 3-Dimensional; Acceleration; Adult; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Amyloid; Biological Markers; Brain; Brain region; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Clinic; Clinical Research; Clinical Trials; Cognitive; Consumption; Contrast Media; Data; Dementia; Differential Diagnosis; Disease; Early Diagnosis; Elderly; Ensure; Evaluation; Glucose; Guidelines; Impaired cognition; Individual; Ionizing radiation; Magnetic Resonance Imaging; Maps; Measures; Methods; Microvascular Dysfunction; Modality; Morphologic artifacts; Motion; Multi-site clinical study; Nerve Degeneration; Neurons; Outcome Assessment; Paper; Pathology; Patients; Pattern; Perfusion; Play; Population; Positron-Emission Tomography; Protocols documentation; Reference Standards; Reproducibility; Research; Role; Scanning; Serum; Severities; Signal Transduction; Site; Staging; Standardization; System; Techniques; Testing; Time; Tracer; Vascular Diseases; Vendor; Visit; Water; Work; arterial spin labeling; blood flow measurement; clinical application; cognitive function; cognitive testing; cost effective; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; hemodynamics; hypoperfusion; imaging biomarker; mild cognitive impairment; neuroimaging; neurovascular coupling; perfusion imaging; prognostication; reconstruction; tau Proteins; temporal measurement; treatment trial; volunteer

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.

项目摘要 阿尔茨海默病（Alzheimer's Disease，AD）是老年人痴呆的主要病因。成像生物标志物 已经在PET上建立了相应的示踪剂，用于绘制淀粉样蛋白和tau的积累，以及 神经变性此外，脑血管疾病（CVD）和AD之间存在相当大的重叠， 提示两种病理对认知衰退的相加或协同作用。血管功能障碍也 被认为是更好地理解和表征这种多因素的重要生物标志物。 疾病神经变性和血管功能障碍的可靠映射可能在许多疾病中发挥关键作用。 临床应用。脑血流量（CBF）是表征脑缺血的基本血液动力学参数， 脑灌注作为神经功能的替代物和小血管疾病的标志物。动脉自旋 标记（ASL）灌注MRI提供了不需要外源性造影剂的巨大优势， 没有电离辐射。在一次就诊中同时获得结构MRI和灌注MRI， 非常适合于扫描老年受试者。空间选择性脑血流图的解释 由于动脉血流缓慢，ASL方法需要谨慎对待人工灌注不足。 老科目。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， 用于多站点跨供应商的标准化、可靠且经过验证的基于ASL的CBF映射协议 AD的神经影像学研究。速度选择性ASL（VSASL）导出的CBF图非常适合于 老年人群中神经变性和血管功能障碍的特征， 受到缓慢流动的限制。我们已经实现了第一个速度选择反演 (VSI)基于VSASL的成人大脑三维采集，并证明其对灌注的敏感性更高 信号超过传统ASL方法。拟议的工作利用了VSI的高灌注敏感性， ASL被VSASL的第一份指南文件所认可，并加速了采集和重建 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， 加速采购和重建，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再现性和有效性（目标2）;表征VSI-ASL 认知正常（CN）受试者以及MCI和AD患者不同脑区的衍生CBF值 通过横向和纵向比较（目标3）。我们将展示优化的3D VSI-ASL技术具有较高的重现性、有效性和灵敏度，可检测脑灌注变化， 神经退行性变，它可以很容易地用作一个更实用和成本效益的成像生物标志物， 神经退行性变和血管功能障碍，用于AD和ADRD的多中心和多供应商临床研究。