Assessing Mitochondrial Metabolism by Magnetization Transfer MR Fingerprinting

描述（申请人提供）：磁共振波谱（MRS）提供了一个强大的工具来询问组织代谢的各个方面。特别是，磷-31 （31P）磁化转移光谱（MT-MRS）早已被提出作为一种测量体内ATP合成速率的手段。然而，目前的31P MT-MRS方法需要非常长的数据采集时间才能准确地量化ATP合成速率。另一方面，磁共振指纹（MRF）方法的最新发展提供了一种全新的数据采集框架，可以同时测量多种组织特性，包括松弛时间，大大缩短了采集时间。MT-MRS中化学交换速率的测量涉及表观弛豫时间（T1app）的测量，即化学交换修饰的T1弛豫时间，这与质子成像中T1的测量高度相似。因此，本提案的总体目标是开发和验证新的31P MT-MRF技术，以快速准确地定量心脏中ATP的合成速率。这个项目有两个具体目标。目标1分为三个部分：1)通过计算机仿真设计和评估31P MT-MRF方法；2)在幻体实验中实施和优化31P MT-MRF方法，3)在不同负荷下，在灌注心脏中对比已建立的31P MT-MRS方法验证31P MT-MRF方法。在目标2中，将研究用31P MT-MRF进行化学交换率空间分辨测量的可行性。将开发一种压缩传感螺旋31P化学位移成像（CSI）序列，该序列将比笛卡尔CSI方法产生92倍的加速度。31P MT-MRF CSI方法将在大鼠骨骼肌缺血再灌注损伤模型中进行验证。本临床前项目开发的方法将为临床方法的发展奠定基础，这些方法可用于评估糖尿病、肥胖症等多种代谢疾病的代谢功能。

DESCRIPTION (provided by applicant): Magnetic Resonance Spectroscopy (MRS) provides a powerful tool to interrogate various aspects to tissue metabolism. In particular, phosphorus-31 (31P) magnetization transfer spectroscopy (MT-MRS) has long been proposed as a means of measuring ATP synthesis rate in vivo. However, current 31P MT-MRS methods require prohibitively long data acquisition time to accurately quantify ATP synthesis rate. On the other hand, recent development of magnetic resonance fingerprinting (MRF) method provides a completely new framework of data acquisition that allows simultaneous measurement of several tissue properties, including relaxation times, at drastically reduced acquisition time. The measurement of chemical exchange rate in MT-MRS involves the measurement of the apparent relaxation time (T1app), i.e., the chemical exchange modified T1 relaxation, which is highly analogous to the measurement of T1 in proton imaging. Therefore, the overall objective of this proposal is to develop and validate novel 31P MT-MRF technique for fast and accurate quantification of ATP synthesis rate in hearts. This project has two specific aims. Aim 1 has three parts: 1) designing and evaluating 31P MT-MRF methods by computer simulation; 2) implementing and optimizing the 31P MT-MRF methods in phantom experiments, and 3) validating the 31P MT-MRF methods against established 31P MT-MRS methods in perfused hearts under varying workload. In Aim 2, the feasibility of performing spatially resolved measurement of chemical exchange rate by 31P MT-MRF will be investigated. A compressed sensing spiral 31P chemical shift imaging (CSI) sequence will be developed that will lead to 92-fold acceleration over the Cartesian CSI method. The 31P MT-MRF CSI method will be validated in rat model of ischemia/reperfusion injury in skeletal muscle. Methods developed in this pre-clinical project will lay the foundation for the development of clinical methods that can be applied to evaluating metabolic function in a variety of metabolic diseases such as diabetes and obesity.