CERT Imaging of Muscle

描述(由申请人提供)：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)方法，用于绘制组织pH、磷酸肌酸(PCr)和肌酸(Cr)含量的地图，并应用该方法来表征运动诱导的健康和疾病状态下肌肉代谢的变化。评估这些基本生物物理特征的能力将在临床和临床前有广泛的应用。这些疾病包括糖原储存疾病、糖尿病，尤其是外周动脉疾病(PAD)，这是一种以血流和固有肌肉线粒体缺陷为特征的疾病。为了实现这一目标，建议的方法包括对化学交换饱和转移(CEST)成像进行重大和新颖的重新制定。在广泛应用CEST方法方面存在固有的和关键的技术障碍，在实践中使用这些方法也存在重大限制。CEST缺乏定量，并且非常容易受到静电场中脂质含量不均匀、多个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引起的伪影的影响。化学交换旋转转移(CERT)是我们提出的CEST的新公式，它克服了CEST的缺点。此外，CERT可以起到汇率过滤器的作用，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)开发、优化和验证CERT成像方法；2)在不同铬含量和运动的大鼠模型中量化组织的聚合酶链式反应、铬含量和pH值的变化；以及3)在人体运动和外周动脉疾病的研究中量化聚合酶链式反应的组织变化以及铬含量和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.