Intracranial Vascular Compliance as an Early Imaging Marker of Alzheimer's Disease

颅内血管顺应性作为阿尔茨海默病的早期成像标志

• 批准号: 9370755
• 负责人: Lirong Yan
• 金额: $ 15.07万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9370755
• 关键词: 3-Dimensional; Abeta clearance; Address; Age; Alleles; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Arteries; Assessment tool; Biological Markers; Biophysics; Blood - brain barrier anatomy; Blood Vessels; Brain; Cause of Death; Cerebral Amyloid Angiopathy; Cerebrovascular Disorders; Clinical; Clinical Research; Cognitive; Cross-Sectional Studies; Data; Development; Disease Marker; Early Diagnosis; Elderly; Event; Exhibits; Exposure to; Functional disorder; Genotype; Goals; Head; Healthcare; Image; Impaired cognition; Impairment; K-Series Research Career Programs; Knowledge; Learning; Magnetic Resonance Imaging; Measurement; Measures; Methodology; Methods; Motion; Nerve Degeneration; Neurodegenerative Disorders; Noise; Outcome; Pathogenesis; Pathology; Patients; Peripheral; Physiologic pulse; Play; Progressive Disease; Reproducibility; Research; Research Personnel; Role; Science; Signal Transduction; Spin Labels; Symptoms; Techniques; Testing; Therapeutic; Time; Training; Translating; United States; Vascular Diseases; Work; abeta deposition; age related; apolipoprotein E-4; arterial stiffness; arteriole; base; bioimaging; brain parenchyma; cerebrovascular; clinical application; cohort; design; genetic risk factor; imaging biomarker; improved; indexing; mild cognitive impairment; neuroimaging; novel; peptide B; pre-clinical; prevent; tau Proteins; tau-1; therapy development; training opportunity; translational study; two-dimensional; vascular contributions

PROJECT SUMMARY/ABSTRACT The proposed work is designed to prepare the applicant with training necessary to establish an independent investigator in the field of interdisciplinary biomedical imaging science, with particular focus on MRI-based assessment of neurodegenerative disease. The central core of the training will involve closing the gap between the applicant's biophysics background and her limited exposure to pathophysiology and clinical research in order to enhance understanding of the clinical implications and biomedical needs of novel MRI techniques toward translating imaging methodology to the clinical applications. Early diagnosis of Alzheimer's disease (AD) is critical for developing therapeutic strategies to prevent, slow or even halt progressive disease. A growing body of evidence suggests cerebrovascular dysfunction may occur relatively early and proceeds the cognitive decline and onset of neurodegenerative changes in AD. Vascular compliance (VC) or arterial stiffness is an important indicator of vascular dysfunction. Currently, VC can be only assessed from central and peripheral arteries using pulse wave velocity (PWV). Recently, we have developed a non-invasive MRI technique for assessment of intracranial VC using dynamic arterial spin labeling (ASL). The goal of the research component of this proposal is to further develop and optimize the noninvasive intracranial VC techniques, and to evaluate intracranial VC as an early imaging marker by comparison with other established biomarkers. We hypothesize that intracranial VC is able to serve as an early imaging marker in the development of AD. The hypotheses will be addressed with the following three specific aims: 1) We will further develop and optimize the intracranial VC technique to improve the reliability of VC measurement. 2) We design a cross-sectional study to measure and compare intracranial VC in four age-equivalent groups including cognitively normal (CN) and mild cognitive impairment (MCI), with and without APOE 4 genotype. 3) We correlate intracranial VC with the established AD biomarkers. The expected outcome is a noninvasive MRI tool for assessment of intracranial VC or arterial stiffness, and developing intracranial VC as an early imaging marker of AD, which may deepen our understanding of cerebrovascular contributions to AD pathogenesis. This career development award will provide the applicant necessary training to integrate her expertise with clinical translational studies and develop into an independent investigator.

项目概要/摘要 拟议的工作旨在帮助申请人做好建立独立机构所需的培训 跨学科生物医学成像科学领域的研究者，特别关注基于 MRI 的 神经退行性疾病的评估。培训的核心将涉及缩小之间的差距 申请人的生物物理学背景以及她对病理生理学和临床研究的有限了解 为了增强对新型 MRI 技术的临床意义和生物医学需求的理解 将成像方法转化为临床应用。阿尔茨海默病的早期诊断 (AD) 对于制定预防、减缓甚至阻止疾病进展的治疗策略至关重要。一个 越来越多的证据表明，脑血管功能障碍可能发生得相对较早，并且会继续发展 AD 中认知能力下降和神经退行性改变的发生。血管顺应性 (VC) 或动脉 僵硬度是血管功能障碍的重要指标。目前，VC只能从中央和 使用脉搏波速度 (PWV) 检测外周动脉。最近，我们开发了一种非侵入性MRI 使用动态动脉自旋标记 (ASL) 评估颅内 VC 的技术。的目标 该提案的研究部分是进一步开发和优化无创颅内 VC 技术，并通过与其他已建立的技术比较来评估颅内 VC 作为早期成像标志物的作用 生物标志物。我们假设颅内 VC 能够作为早期影像学标志物 AD的发展。这些假设将通过以下三个具体目标来解决：1）我们将进一步 开发和优化颅内VC技术，提高VC测量的可靠性。 2）我们设计 一项横断面研究，测量和比较四个年龄相当组的颅内 VC，包括 认知正常 (CN) 和轻度认知障碍 (MCI)，有或没有 APOE 4 基因型。 3）我们 将颅内 VC 与已建立的 AD 生物标志物相关联。预期结果是一种无创 MRI 工具 用于评估颅内 VC 或动脉僵硬度，并开发颅内 VC 作为早期成像 AD 的标志物，这可能会加深我们对脑血管对 AD 发病机制的贡献的理解。这 职业发展奖将为申请人提供必要的培训，将其专业知识与临床相结合 转化研究并发展成为一名独立研究者。