CERT Imaging of Cancer

描述（由申请人提供）： 该提案的总体目标是开发和验证一种新的磁共振成像方法，用于映射组织蛋白质和肌酸含量，以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， 特别是因为这些基本生物物理特征与已发现的特征非常不同， 在周围的正常组织中，并且与通常在治疗过程中晚得多地改变的总肿瘤体积的常规测定相比，可以用作治疗反应的改进的早期指标。为实现这一目标，提出的方法包括一个显着的和新颖的化学交换饱和转移（CEST）成像的重新制定。有固有的和关键的技术障碍，广泛应用的CEST方法和重大的限制，他们在实践中使用。CEST缺乏定量，并且非常容易受到源于静态场不均匀性脂质含量、多种代谢物信号的光谱重叠和固有不对称背景大分子共振的伪影的影响。化学交换旋转转移（CERT）是我们提出的CEST的改造，克服了CEST的缺点。此外，CERT可以充当交换率过滤器，并且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）量化肿瘤生长和缓解的大鼠模型中蛋白质和肌酸含量的组织变化; 3）量化接受贝伐单抗治疗的癌症患者中蛋白质和肌酸含量的组织变化，贝伐单抗可恢复血脑屏障并消除炎症，因此使传统的造影后T1和扩散成像无法提供信息。

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.