Non-invasive Magnetic Resonance Imaging of Glycogen in the Human Liver

人类肝脏中糖原的无创磁共振成像

• 批准号: 10727928
• 负责人: Xiang Xu
• 金额: $ 21.13万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10727928
• 关键词: 3-Dimensional; Affect; Amides; Biological Assay; Blood Glucose; Brain imaging; Breathing; Chemicals; Circulation; Clinical; Creatine; Deposition; Detection; Development; Diabetes Mellitus; Disease; Ensure; Fasting; Fatty acid glycerol esters; Frequencies; Glucagon; Glucose; Glycogen; Glycogen Storage Disease; Goals; Health; Hour; Human; Image; Imaging Techniques; Imaging technology; Individual; Injections; Insulin; Intramuscular; Label; Lipids; Liver; Liver Cirrhosis; Liver Glycogen; Magnetic Resonance Imaging; Measurement; Measures; Methods; Morphologic artifacts; Motion; Mus; NMR Spectroscopy; Nuclear; Nuclear Magnetic Resonance; Organ; Patients; Polymers; Preparation; Process; Protocols documentation; Protons; Radial; Reporting; Scanning; Scheme; Signal Transduction; Spectrum Analysis; Speed; Spottings; Structure; Techniques; Testing; Time; Translations; Validation; Water; bariatric surgery; blood glucose regulation; clinical translation; experimental study; glucose metabolism; glycogen metabolism; glycogenolysis; healthy volunteer; image reconstruction; imaging approach; improved; in vivo; liver biopsy; liver imaging; nuclear Overhauser enhancement; prevent; process optimization; reconstruction; stability testing; technique development; temporal measurement

Project Summary The liver is responsible for maintaining blood glucose homeostasis. It is able to deposit large amounts of glucose in the form of glycogen and release glucose rapidly from its glycogen storage when needed. The hepatic glycogen metabolism maybe altered in diseases such as glycogen storage disorders, diabetes mellitus, and liver cirrhosis. Liver biopsy allows direct quantification of glycogen concentration, but it is highly invasive and cannot easily be repeated. 13C nuclear magnetic resonance (NMR) spectroscopy provides a non-invasive way to detect glycogen in the liver, but it is not clinically feasible due to the requirement of specialized imaging hardware. Recently, we have discovered a new contrast mechanism that allows the detection of glycogen based on its nuclear Overhauser enhancement (GlycoNOE). This method enables us to detect glycogen in vivo using standard MRI hardware. In our initial mice study, we found a linear relationship between glycoNOE signal and glycogen concentration and demonstrated that the change in liver glycogen could be measured dynamically. In this project, we aim to develop a new imaging technique to utilize this contrast mechanism in the human liver. To achieve this we will (1) develop and optimize a fast, 3D free-breathing, fat-water separated imaging approach that is suitable for glycoNOE detection in the human liver; (2) compare the NOE signal measured at fed and fasting state to validate that the change in signal reflects the change in glycogen content; and (3) dynamically measure the change of glycogen upon glucagon injection, which further validates the glycoNOE signal and also measures the rate of glycogen degradation. The new imaging technology will be applicable to brain and body imaging based on the nuclear Overhauser enhancement / chemical exchange processes. By providing a non-invasive, real time measure of the change in glycogen level in the liver, it will be possible to study glycogen metabolism in health and in diseases such as diabetes mellitus, glycogen storage diseases, and other liver conditions.

项目概要 肝脏负责维持血糖稳态。它能够在体内沉积大量的葡萄糖 形式的糖原，并在需要时从其糖原储存中快速释放葡萄糖。肝糖原代谢 可能在糖原储存障碍、糖尿病和肝硬化等疾病中发生改变。肝活检允许 直接定量糖原浓度，但它具有高度侵入性并且不易重复。 13C核 磁共振（NMR）波谱提供了一种非侵入性的方法来检测肝脏中的糖原，但它并不是 由于需要专门的成像硬件，因此在临床上可行。最近，我们发现了一个新的对比 允许基于其核 Overhauser 增强 (GlycoNOE) 检测糖原的机制。这 方法使我们能够使用标准 MRI 硬件检测体内糖原。在我们最初的小鼠研究中，我们发现了一个线性的 糖NOE信号与糖原浓度之间的关系，并证明肝糖原的变化 可以动态测量。在这个项目中，我们的目标是开发一种新的成像技术来利用这种对比度 人体肝脏中的机制。为了实现这一目标，我们将 (1) 开发和优化快速、3D 自由呼吸、脂肪-水 适用于人类肝脏中 aminoNOE 检测的分离成像方法； (2)比较NOE信号 在进食和禁食状态下进行测量，以验证信号的变化反映了糖原含量的变化；和（3） 动态测量胰高血糖素注射后糖原的变化，进一步验证 angioNOE 信号和 还测量糖原降解率。新的成像技术将适用于大脑和身体 基于核奥弗豪瑟增强/化学交换过程的成像。通过提供非侵入性、 实时测量肝脏中糖原水平的变化，为研究健康状态下的糖原代谢提供了可能 以及糖尿病、糖原贮积病和其他肝脏疾病等疾病。