Assessing Mitochondrial Metabolism by Magnetization Transfer MR Fingerprinting

描述（由申请人提供）：磁共振波谱（MRS）提供了一种强有力的工具来询问组织代谢的各个方面。特别是，磷-31（31 P）磁化转移光谱（MT-MRS）长期以来一直被提出作为测量体内ATP合成速率的手段。然而，目前的31 P MT-MRS方法需要非常长的数据采集时间来准确地量化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个全新的数据采集框架，允许同时测量几个组织的属性，包括弛豫时间，在大大减少的采集时间。MT-MRS中化学交换速率的测量涉及表观弛豫时间（T1 app）的测量，即，化学交换修改的T1弛豫，这与质子成像中的T1测量高度相似。因此，本提案的总体目标是开发和验证用于快速准确定量心脏ATP合成速率的新型31 P MT-MRF技术。该项目有两个具体目标。目标1有三个部分：1）通过计算机模拟设计和评估31 P MT-MRF方法; 2）在体模实验中实施和优化31 P MT-MRF方法; 3）在不同工作负荷下在灌注心脏中验证31 P MT-MRF方法与已建立的31 P MT-MRS方法。在目标2中，将研究通过31 P MT-MRF进行化学交换速率的空间分辨测量的可行性。将开发压缩感知螺旋31 P化学位移成像（CSI）序列，其将导致笛卡尔CSI方法的92倍加速。将在骨骼肌缺血/再灌注损伤大鼠模型中验证31 P MT-MRF CSI方法。在这个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疾病（如糖尿病和肥胖症）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.