Quantitative Measurement of Cerebrovascular Permeability in Early Dementia

早期痴呆脑血管通透性的定量测量

• 批准号: 8306203
• 负责人: VALERIE C ANDERSON
• 金额: $ 14.1万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306203
• 关键词: Active Biological Transport; Aging; Alleles; Alzheimer' s Disease; Amyloid; Anatomy; Apolipoprotein E; Area; Biological Markers; Biomedical Research; Blood - brain barrier anatomy; Blood Vessels; Blood Volume; Blood capillaries; Bolus Infusion; Brain; Cessation of life; Clinical; Cognitive; Data; Dementia; Development; Diffusion; Disease; Drug Kinetics; Elderly; Exposure to; Extravasation; Functional disorder; Funding; Goals; Health; Hippocampus (Brain); Human; Image; Impaired cognition; Injection of therapeutic agent; Investigation; K-Series Research Career Programs; Knowledge; Lead; Lesion; Life; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medial; Medical; Membrane; Memory; Mentors; Methodology; Microvascular Permeability; Molecular Weight; Neurofibrillary Tangles; Neuronal Injury; Oxidative Stress; Pathogenesis; Pathology; Patients; Performance; Permeability; Physiological; Physiology; Play; Positioning Attribute; Prevalence; Property; Protons; Quality of life; Reagent; Relaxation; Research; Resolution; Risk; Risk Factors; Role; Senile Plaques; Staging; Structure; Surface; Techniques; Temporal Lobe; Therapeutic Intervention; Time; Tissues; Training; Training Programs; Translations; Variant; Vascular Permeabilities; Water; Water Movements; Work; aged; aging brain; base; bioimaging; capillary; career; cerebrovascular; clinically significant; computerized data processing; density; experience; gray matter; healthy aging; hemodynamics; improved; in vivo; meetings; pharmacokinetic model; public health relevance; spatiotemporal; tau Proteins; water channel; white matter; white matter change

DESCRIPTION (provided by applicant): This application proposes a training program to integrate the PI's previous research efforts into investigations of aging and Alzheimer's disease (AD). Much of Dr. Anderson's previous research has involved methodologies related to biomedicine, but has been done with only a basic understanding of the clinical needs and complexities. The proposed project would provide a broad experiential mentoring experience focused on clinical aspects of aging and AD, as well as added knowledge in vascular physiology and high field magnetic resonance imaging (MRI). The overall goal is to expand the PI's experience and training in biomedicine and bioimaging to position her for a career in biomedical research. Alzheimer's disease is the most common form of dementia in the elderly. Although traditionally considered a disease of neurofibrillary tangles and amyloid plaques, cerebrovascular structure and function is profoundly altered in AD and may contribute directly to oxidative stress, neuronal injury and death. Many older demented patients not meeting common pathological criteria for AD may have dementia on a microvascular basis that is not readily appreciated. Since vascular dysfunction often precedes cognitive impairment, understanding the role of vascular abnormalities in AD pathogenesis is critical to the rational treatment of the disease. Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of vessel integrity in the living human brain. The long-term goal of this project is to quantify with high precision and accuracy the microvascular properties of the human brain along the healthy aging-AD continuum. The specific aims are to: (1) define the microvascular properties of the early AD and healthy aged brain; (2) define a 'microvascular permeability' network in early AD; and (3) examine the capillary integrity of white matter lesions in the healthy aged and mild AD brain. To maximize the spatiotemporal resolution, DCE-MRI studies will be performed at 7T. We anticipate that use of this ultra-high field will lead to substantial improvement in the precision and accuracy of pharmacokinetic parameters and the maps derived from them. These maps provide the key to translation of advanced MR techniques to the identification of new imaging biomarkers of incipient AD. PUBLIC HEALTH RELEVANCE: The proposed project will yield precise, accurate in vivo measures of vascular permeability and will map at high resolution the microvascular properties of the early Alzheimer's disease (AD) and cognitively unimpaired elderly brain. This knowledge could improve our understanding of the transition from healthy brain aging to dementia and suggest new imaging biomarkers of incipient AD.

描述（由申请人提供）：本申请提出了一项培训计划，以将PI先前的研究工作整合到对衰老和阿尔茨海默氏病（AD）的研究中。安德森博士以前的大部分研究都涉及与生物医学有关的方法，但仅对临床需求和复杂性有基本的理解。拟议的项目将提供广泛的体验指导经验，专注于衰老和AD的临床方面，并增加了有关血管生理和高场磁共振成像（MRI）的知识。总体目标是扩大PI在生物医学和生物成像中的经验和培训，以将她定位为生物医学研究的职业。 阿尔茨海默氏病是老年痴呆症最常见的形式。尽管传统上认为是神经原纤维缠结和淀粉样斑块的疾病，但脑血管结构和功能在AD中发生了深刻的改变，并且可能直接导致氧化应激，神经元损伤和死亡。许多不符合AD的常见病理标准的老年痴呆症患者可能会在微血管基础上具有痴呆症，这是不容易理解的。由于血管功能障碍通常在认知障碍之前先于认知障碍，因此了解血管异常在AD发病机理中的作用对于该疾病的合理治疗至关重要。动态对比增强的MRI（DCE-MRI）提供了活体大脑中血管完整性的定量度量。该项目的长期目标是以高精度和准确的量化沿健康的衰老AD连续体的人脑的微血管特性进行量化。具体目的是：（1）定义早期AD和健康老化大脑的微血管特性； （2）在AD早期定义一个“微血管通透性”网络； （3）检查健康老化和轻度AD大脑中白质病变的毛细血管完整性。为了最大化时空分辨率，DCE-MRI研究将在7T下进行。我们预计，使用这种超高场将导致药代动力学参数的精确性和准确性以及从中得出的地图的准确性和准确性的显着提高。这些地图为将高级MR技术转换为鉴定初始AD的新成像生物标志物提供了关键。 公共卫生相关性：拟议的项目将产生精确，准确的体内血管通透性度量，并以高分辨率绘制高分辨率的阿尔茨海默氏病（AD）的微血管特性（AD）和认知没有影响的老年人大脑。这些知识可以提高我们对从健康的大脑衰老到痴呆症的过渡，并提出新的成像生物标志物。