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

项目摘要 肝脏负责维持血糖稳态。它能够将大量的葡萄糖存款在 葡萄糖是糖原的一种形式，并在需要时迅速从其糖原储存中释放葡萄糖。肝糖原代谢 可能在诸如糖原储存障碍、糖尿病和肝硬化的疾病中改变。肝活检可以 直接定量糖原浓度，但它是高度侵入性的，不能轻易重复。13 C核 磁共振（NMR）光谱提供了一种非侵入性的方法来检测肝脏中的糖原，但它不是 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 这种机制允许基于其核欧沃豪泽增强（GlycoNOE）检测糖原。这 方法使我们能够检测糖原在体内使用标准的MRI硬件。在我们最初的小鼠研究中，我们发现了一种线性的 glycoNOE信号和糖原浓度之间的关系，并证明了肝糖原的变化 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，利用这种对比度 人体肝脏的机制。为了实现这一目标，我们将（1）开发和优化一个快速，3D自由呼吸，脂肪水 分离成像方法，适用于人肝脏中的glycoNOE检测;（2）比较NOE信号 在进食和空腹状态下测量，以验证信号的变化反映糖原含量的变化;以及（3） 动态测量胰高血糖素注射后糖原的变化，这进一步验证了glycoNOE信号， 还测量糖原降解的速率。新的成像技术将适用于大脑和身体 基于核Overhauser增强/化学交换过程的成像。通过提供一种非侵入性， 真实的时间测量肝脏中糖原水平的变化，将有可能研究健康的糖原代谢 以及在疾病如糖尿病、糖原累积病和其它肝脏疾病中的应用。

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.