CERT Imaging of Cancer

描述(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方法，用于绘制组织蛋白质和肌酸含量图，以便检测和表征肿瘤细胞和代谢特征。评估这种肿瘤属性的能力将具有广泛的临床和临床前应用， 尤其是因为这些基本的生物物理特征与已发现的 与常规的大体肿瘤体积测定相比，它可以作为更好的早期治疗反应指标，后者在治疗过程中往往会发生很大的变化。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可以作为汇率过滤器，并可以将肌酸的贡献与其他重叠代谢物的贡献分开。我们将1)开发、优化和验证CERT成像方法；2)在肿瘤生长和缓解的大鼠模型中量化蛋白质和肌酸含量的组织变化；以及3)定量使用贝伐单抗治疗癌症患者的组织蛋白质和肌酸含量的变化，贝伐单抗可以恢复血脑屏障，消除炎症，因此使传统的增强后T1和扩散成像没有信息量。

DESCRIPTION (provided by applicant): The overall goals of this proposal are to develop and validate a novel magnetic resonance imaging method for mapping tissue protein and creatine content in order to detect and characterize tumor cellular and metabolic features. The ability to assess such tumor attributes will have a broad range of both clinical and preclinical applications, particularly since such fundamental biophysical characteristics are highly dissimilar to that found in the surrounding normal tissue and could serve as improved early indicators of treatment response as compared to conventional assays of gross tumor volume, which often change much later in the course of therapy. 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 creatine from that of other overlapping metabolites. We will 1) develop, optimize, and validate CERT imaging methods; 2) quantify tissue changes in protein and creatine content in rat models of tumor growth and remission; and 3) quantify tissue changes in protein and creatine content in cancer patients treated with Bevacizumab, which restores the blood brain barrier and eliminates inflammation, and hence makes conventional post-contrast T1 and diffusion imaging uninformative.