MRI in mouse models of heart disease

小鼠心脏病模型中的 MRI

• 批准号: 9093799
• 负责人: Frederick H Epstein
• 金额: $ 34.58万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-05 至 2017-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9093799
• 关键词: Acceleration; Activities of Daily Living; Advanced Glycosylation End Products; Adverse event; Animals; Biology; Blood Vessels; Blood flow; Cardiac; Cardiovascular system; Cells; Chronic; Complex; Coronary; Coronary Arteriosclerosis; Coronary heart disease; Diabetes Mellitus; Diabetic mouse; Diagnostic Factor; Disease; Environment; Enzymes; Epidemic; Evaluation; Exhibits; Functional disorder; Funding; Gadolinium; Gene Proteins; Gene-Modified; Goals; Gold; Health; Heart; Heart Diseases; Heart Rate; Human; Hyperglycemia; Image; Imaging Techniques; Individual; Infarction; Interobserver Variability; Intraobserver Variability; Kinetics; Lead; Left Ventricular Remodeling; Link; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Methods; Microspheres; Microvascular Dysfunction; Modeling; Molecular; Morphologic artifacts; Motion; Mus; Myocardial; Myocardial Ischemia; Nature; Nitric Oxide Synthase Type I; Obesity; Organ; Organism; Patients; Physiological; Physiology; Prognostic Factor; Reproducibility; Resolution; Respiration; Rest; Role; Scanning; Secondary to; Spin Labels; Stress; Techniques; Testing; Time; Tissues; Tracer; Vascular Diseases; body system; contrast enhanced; diabetic; gadolinium oxide; gene product; imaging modality; improved; in vivo; macrovascular disease; mouse model; new therapeutic target; novel; prognostic; quantitative imaging; receptor; receptor for advanced glycation endproducts; research study; therapeutic target; tool; validation studies; vascular bed

DESCRIPTION (provided by applicant): Measurements of myocardial blood flow (MBF) and contractile function are essential to the evaluation of coronary heart disease (CHD). While compromised contractile function occurs as CHD advances, a growing concept is that coronary microvascular disease with impaired MBF reserve is an early marker of CHD, is prognostic of adverse events, and is potentially causal of additional coronary vascular disease, such as in the setting of diabetes with hyperglycemia. Due to the ready availability of genetically-manipulated animals, mouse models are widely used to investigate molecular mechanisms underlying CHD. We previously developed cine DENSE MRI to quantify contractile function in mice with high accuracy, resolution, and ease of analysis. We also applied multi-parametric MRI in gene-modified mice to elucidate the roles of various receptors and enzymes in normal cardiac function and in post-infarct left-ventricular remodeling. Next, we propose to focus on imaging to elucidate mechanisms underlying coronary microvascular dysfunction by assessment of MBF in mice. Basic MBF imaging in mice using first-pass MRI and arterial spin labeling (ASL) have previously been demonstrated by us and others, however, through acceleration using compressed sensing (CS) and improved tracer kinetic modeling, we propose to develop substantial improvements to spatial resolution, scan time, and quantitation. Furthermore, we propose comparison studies to determine which method is most accurate and reproducible. Subsequently, we propose to apply MBF imaging in hyperglycemic diabetic mice (Akita mice), where we will test the hypothesis that advanced glycation end products (AGEs) and the receptor for AGE (RAGE) mediate hyperglycemic coronary microvascular dysfunction. To accomplish these goals we have three specific aims. First, we will use novel CS methods to develop (a) a motion-compensated dual-contrast first- pass gadolinium-enhanced MRI technique for MBF imaging in mice and (b) an accelerated ASL MRI technique for high-resolution MBF imaging in less than 10 minutes. In our second aim we will compare and validate first- pass MRI and ASL for MBF imaging in mice, using microspheres as a gold standard. This aim will include reproducibility studies. In our third aim we will use MBF and other imaging to test the hypothesis that RAGE-/- mice are protected from coronary microvascular disease that develops in akita mice. The successful completion of these aims would lead to improved imaging methods for quantifying MBF in mice. In one particular application, MBF imaging would be used to establish the role of RAGE in coronary microvascular disease secondary to diabetic hyperglycemia.

描述（由申请人提供）：心肌血流（MBF）和收缩功能的测量对于评估冠心病（CHD）至关重要。虽然收缩功能损害是随着冠心病的进步而发生的，但越来越多的概念是，患有MBF储备受损的冠状动脉微血管疾病是冠心病的早期标志，是不良事件的预后，并且可能是其他冠状动脉血管疾病的因果，例如在患有超级疾病的糖尿病的情况下。由于遗传操纵动物的现成可用性，小鼠模型被广泛用于研究CHD潜在的分子机制。我们先前开发了Cine致密MRI，以高精度，分辨率和易于分析的性能来量化小鼠的收缩功能。我们还将多参数MRI应用于基因修饰的小鼠中，以阐明各种受体和酶在正常心脏功能以及侵入后左心室重塑中的作用。接下来，我们建议专注于成像，以通过评估小鼠的MBF评估冠状动脉微血管功能障碍。我们和其他人以前已经证明了使用第一通MRI和动脉自旋标记（ASL）在小鼠中的基本MBF成像，但是，通过使用压缩感应（CS）加速并改善了示踪动力学建模，我们建议通过加速进行加速，我们建议开发实质性改进，以改进空间分辨率，扫描时间和定量。此外，我们提出了比较研究，以确定哪种方法最准确和可重复。随后，我们建议在高血糖糖尿病小鼠（Akita小鼠）中应用MBF成像，在那里我们将测试先进的糖基化终产物（AGES）和年龄（RAGE）介导高血糖冠状动脉微血管微血管功能障碍的假说。为了实现这些目标，我们有三个具体的目标。首先，我们将使用新颖的CS方法来开发（a）运动补偿双对比度第一次通过Gadolinium增强的MRI技术，用于小鼠中的MBF成像，以及（b）在不到10分钟内进行高分辨率MBF成像的加速ASL MRI MRI技术。在第二个目标中，我们将使用微球作为金标准来比较和验证小鼠中MBF成像的第一次通过MRI和ASL。这个目标将包括可重复性研究。在我们的第三个目标中，我们将使用MBF和其他成像来测试愤怒 - / - 小鼠免受秋田小鼠发展的冠状动脉微血管疾病的假设。这些目标的成功完成将导致改进的成像方法来量化小鼠的MBF。在一种特定的应用中，MBF成像将用于确定愤怒在继发于糖尿病高血糖的冠状动脉微血管疾病中的作用。