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.

项目摘要/摘要 拟议的工作旨在为申请人准备必要的培训以建立独立的培训 跨学科生物医学成像科学领域的研究者，特别关注基于MRI 评估神经退行性疾病。培训的核心将涉及缩小 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暴露有限 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 阿尔茨海默氏病的早期诊断 （AD）对于制定治疗策略至关重要，以预防，缓慢甚至停止进行性疾病。一个 越来越多的证据表明，脑血管功能障碍可能相对较早，并进行 AD中神经退行性变化的认知能力下降和发作。血管合规性（VC）或动脉 刚度是血管功能障碍的重要指标。目前，VC只能从中央和 使用脉冲波速度（PWV）的外围动脉。最近，我们开发了非侵入性MRI 使用动态动脉自旋标记（ASL）评估颅内VC的技术。目标的目标 该提案的研究组成部分是进一步开发和优化非侵入性颅内VC 通过与其他已建立的相比，技术，并评估颅内VC作为早期成像标记 生物标志物。我们假设颅内VC能够充当早期成像标记 广告的开发。假设将以以下三个特定目的解决：1）我们将进一步 开发和优化颅内VC技术，以提高VC测量的可靠性。 2）我们设计 一项横断面的研究，以测量和比较四个年龄等效组的颅内VC 具有和无APOE4基因型的认知正常（CN）和轻度认知障碍（MCI）。 3）我们 将颅内VC与已建立的AD生物标志物相关。预期的结果是无创的MRI工具 用于评估颅内VC或动脉刚度，并发展为早期成像的颅内VC AD的标记，这可以加深我们对脑血管对AD发病机理的贡献的理解。这 职业发展奖将提供必要的培训，以将她的专业知识与临床融合在一起 翻译研究并发展成为独立的研究者。