CERT Imaging of Muscle

描述（由申请人提供）：本提案的总体目标是开发和验证一种新的磁共振成像（MRI）方法，用于绘制组织pH值、磷酸肌酸（PCr）和肌酸（Cr）含量，并应用该方法表征健康和患病状态下运动引起的肌肉代谢变化。评估这些基本生物物理特征的能力将具有广泛的临床和临床前应用。这些疾病包括糖原储存疾病、糖尿病，以及最值得注意的外周动脉疾病（PAD），这是一种以血流和内在肌肉线粒体缺陷为特征的疾病。提出的实现这一目标的方法包括化学交换饱和转移（CEST）成像的重要和新颖的重新配方。广泛应用无害环境技术方法存在固有和关键的技术障碍，在实践中使用这些方法也受到重大限制。CEST缺乏量化，极易受到静态场不均匀性、脂质含量、多种代谢物信号的光谱重叠以及固有的不对称背景大分子共振等因素的影响。化学交换旋转转移（CERT）是我们为克服CEST的不足而提出的CEST的改型。此外，CERT还可以作为汇率过滤器，将Cr的贡献与其他重叠代谢物（如PCr）分离开来。我们将1)开发、优化和验证CERT成像方法；2)量化不同Cr含量和运动大鼠模型组织PCr、Cr含量和pH的变化；3)在人体运动和外周动脉疾病的研究中，定量组织的PCr变化、Cr含量和pH值。

DESCRIPTION (provided by applicant): The overall goals of this proposal are to develop and validate a novel magnetic resonance imaging (MRI) method for mapping tissue pH and phosphocreatine (PCr) and creatine (Cr) content and to apply this method to characterize exercise-induced changes in muscle metabolism in healthy and diseased states. The ability to assess such fundamental biophysical characteristics will have a broad range of clinical and preclinical applications. These include glycogen storage diseases, diabetes, and, most notably for this application, peripheral artery disease (PAD), a disease characterized by blood flow and intrinsic muscle mitochondrial deficits. The proposed methods for achieving this objective include a significant and novel reformulation of chemical exchange saturation transfer (CEST) imaging. There are inherent and critical technical obstacles to the widespread application of CEST methods and major limitations on their use in practice. CEST suffers from a lack of quantification and is highly susceptible to artifacts originating from static field inhomogeneities lipid content, spectral overlap of multiple metabolites signals, and the inherently asymmetric background macromolecular resonance. Chemical exchange rotation transfer (CERT) is our proposed reformulation of CEST that overcomes the shortcomings of CEST. Furthermore, CERT can act as an exchange rate filter and can separate the contribution of Cr from that of other overlapping metabolites, such as PCr. We will 1) develop, optimize, and validate CERT imaging methods; 2) quantify tissue changes in PCr and Cr content and pH in rat models of varied Cr content and exercise; and 3) quantify tissue changes in PCr, and Cr content and pH in human studies of exercise and peripheral artery disease.