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新陈代谢的各个方面。特别是，磷-31(31P)磁化转移光谱(MT-MRS)长期以来一直被认为是测量体内ATP合成速率的一种手段。然而，目前的31P MT-MRS方法需要很长的数据采集时间才能准确地定量ATP合成速率。另一方面，最近发展的磁共振指纹(MRF)方法提供了一种全新的数据采集框架，允许同时测量几种组织属性，包括弛豫时间，大大减少了采集时间。MT-MRS中化学交换率的测量涉及表观驰豫时间(T1app)的测量，即化学交换修正的T1驰豫，它与质子成像中的T1测量高度相似。因此，这项提案的总体目标是开发和验证新的31P MT-MRF技术，用于快速准确地定量心脏中的ATP合成速率。这个项目有两个具体目标。目的1)计算机模拟设计和评价31P MT-MRF方法；2)在体模实验中实现和优化31P MT-MRF方法；3)在不同负荷下，在灌流心脏中验证31P MT-MRF方法和已建立的31P MT-MRS方法。在目标2中，将研究用31P MT-MRF进行化学交换的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，其速度将是笛卡尔CSI方法的92倍。31P MT-MRF CSI方法将在大鼠骨骼肌缺血再灌注损伤模型中得到验证。这一临床前项目中开发的方法将为临床方法的开发奠定基础，这些方法可用于评估各种代谢性疾病的代谢功能，如糖尿病和肥胖症。

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.