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 阿尔茨海默氏病（AD）是老年人口痴呆的主要原因。成像生物标志物 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的积累，以及 神经变性。此外，脑血管疾病（CVD）和AD之间的重叠很大 提出两种病理学对认知能力下降的累加或协同作用。血管功能障碍也有 被认为是更好地理解和表征此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人中起关键作用 临床应用。脑血流（CBF）是一种表征的基本血液动力学参数 脑灌注既是神经功能的替代物，又是小血管疾病的标志物。动脉旋转 标记（ASL）灌注MRI提供了不需要外源对比剂的巨大优势，并且 没有电离辐射。在一次访问诊所中，获得结构性MRI和灌注MRI是 非常需要扫描老年人。从空间选择性得出的CBF地图的解释 ASL方法需要谨慎对人的人造灌注不足，因为缓慢流动通常会发生 较老的主题。尽管在这一领域做了很多努力，但仍有未满足和迫切需要建立 一个标准化，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）衍生的CBF地图非常适合 老年人群中神经退行性和血管功能障碍的表征，没有 遭受缓慢流动所带来的局限性。我们已经实施了第一个速度选择性反转 （VSI）基于3D的基于成人大脑的VSASL，并证明了其对灌注的较高敏感性 传统ASL方法的信号。拟议的工作利用了VSI的高灌注敏感性 ASL由VSASL的第一条准则论文认可，以及加速的收购和重建 策略，代表其第一个广告应用程序。这项研究的目的是用 加速收购和重建，然后确保其多供应商兼容性（AIM 1）；评估 会议，供应商和方式之间的可重复性和有效性（AIM 2）；表征VSI-ASL 认知正常（CN）受试者中各个大脑区域的CBF值，患有MCI和AD的患者 通过横截面和纵向比较（AI​​M 3）。我们将展示优化的3D 具有高可重现性，有效性和灵敏度的VSI-ASL技术，可检测脑灌注变化和 神经变性，可以很容易地用作更实用，更具成本效益的成像生物标志物 用于AD和ADRD的多中心和多供应商临床研究的神经变性和血管功能障碍。