CERT Imaging of Muscle

这项提案的总体目标是开发和验证一种新的磁共振成像(MRI) 一种组织pH、磷酸肌酸和肌酸含量的测绘方法及其应用 描述运动引起的肌肉代谢在健康和疾病状态下的变化。有能力 评估这种基本的生物物理特征将具有广泛的临床和临床前 申请。这些疾病包括糖原储存疾病、糖尿病，最值得注意的是这一应用， 外周动脉疾病(PAD)，一种以血流和固有肌肉线粒体为特征的疾病 赤字。实现这一目标的拟议方法包括一项重大而新颖的重新表述 化学交换饱和转移(CEST)成像。存在固有的和关键的技术障碍 CEST方法的广泛应用及其在实践中使用的主要限制。CEST患上了 缺乏量化，极易受到静电场不均匀、脂质等因素引起的伪影的影响 多个代谢物信号的含量、光谱重叠以及固有的不对称背景 大分子共振。化学交换旋转转移(CERT)是我们提出的 这克服了CEST的缺点。此外，CERT可以充当汇率过滤器，并可以 将铬的贡献与其他重叠代谢物的贡献分开，如聚合酶链式反应。我们将1)发展， 优化和验证CERT成像方法；2)定量检测大鼠组织中聚合酶链式反应、铬含量和pH值的变化 不同铬含量和运动的模型；以及3)量化组织在聚合酶链式反应中的变化，以及铬含量和pH在 运动与外周动脉疾病的人体研究。

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.