Dual Sodium MRI and Proton ADC Assessment of Rodent Glioma Therapy

描述（由申请方提供）：为了提高抗癌治疗期间检测肿瘤反应的可靠性，本项目将评价双钠/质子生物标志物。待检验的中心假设声称，在有效的抗癌治疗期间，Na MRI和肿瘤的质子扩散（ADC）之间存在相关性，因此两种方法均可在可见肿瘤收缩之前预测结果，相反，这些反应在无反应肿瘤或无效治疗期间不同。联合ADC（肿瘤细胞构成的指标）和钠MRI提供了一个机会，可以同时通过癌细胞的两个相关生理维度来评估肿瘤治疗。这些结果对于评估治疗效果至关重要，因此，加强对癌症患者的护理。全脑的逐像素钠/ADC 2D分析将提供肿瘤对治疗的异质反应性的定量图。大鼠胶质瘤模型中的TSC变化可以在任何明显的肿瘤缩小之前一周发生，因此钠MRI具有评估肿瘤治疗结果的预测能力，这将被研究。本课题将对9 L大鼠脑肿瘤在9.4T强磁场下进行多次化疗，研究质子ADC值与3D Na MRI之间的关系。该项目的第二个目标是通过ADC以及通过Na结合（主要是蛋白质）确定的特定总钠池的变化来评估肿瘤治疗。化学性脑肿瘤细胞破坏减少了结合Na的量，这可以通过三重量子Na信号（TQ）检测到。TQ Na信号的变化通常与SQ Na信号的变化方向相反。 预期该特征可补充ADC分析，以区分水肿细胞反应和有效的肿瘤治疗。肿瘤治疗的评估将通过新型钠TQ信号检测来进行。创新包括最佳检测各种Na结合的能力，克服了TQ方法的主要缺点，这些缺点受到检测效率低和存在多种伪影的困扰。总之，将使用钠MRI对肿瘤细胞结构的晚期ADC生物标志物进行广泛评估，目前正在进行临床试验。此外，还包括结合钠的成像，以便于在肿瘤治疗期间区分水肿和细胞崩解。将对应用于肿瘤学的钠MRI进行评价，以便将来转换为高场临床MR扫描仪。

DESCRIPTION (provided by applicant): To advance the reliability of detecting tumor responses during anti-cancer therapy, this project will evaluate a dual sodium/proton biomarker. The central hypothesis to be tested purports that during efficacious anticancer therapy there is a correlation between Na MRI and proton diffusion (ADC) of tumors whereby both methods predict outcome before visible tumor shrinkage and, conversely, these responses differ in nonresponding tumors or during ineffective therapy. Joining ADC, an indicator of tumor cellularity, and sodium MRI provides an opportunity to evaluate tumor therapy by two pertinent physiological dimensions of cancer cells simultaneously. The results are essential for assessing therapeutic efficacy and, consequently, the enhanced care of cancer patients. Pixel by pixel sodium/ADC 2D analysis of the whole brain will provide a quantitative map of heterogeneous responsiveness of a tumor to therapy. The TSC changes in a rat glioma model can take place one week before any noticeable tumor shrinkage, thus sodium MRI has a predictive power for assessing tumor treatment outcome which will be investigated. In this project, the relationship of proton ADC and 3D Na MRI will be performed for a 9L rat brain tumor at a high magnetic field of 9.4 T during several chemotherapies. The second goal of this project is to evaluate tumor therapy by ADC together with changes in a specific pool of total sodium determined by Na binding, mainly to proteins. Chemotherapeutic brain tumor cell destruction decreases the amount of bound Na which is detectable by triple quantum Na signals (TQ). Changes of TQ Na signal are usually in the opposite direction to changes of SQ Na signals. This feature is expected to complement ADC analysis in differentiating between an edematous cell response and efficacious tumor therapy. Assessment of tumor therapy will be performed by novel sodium TQ signal detection. Innovations comprise a capability for optimal detection of a wide range of Na bindings, overcoming the main disadvantages of TQ methods troubled by low detection efficiency and the presence of multiple artifacts. In summary, broad assessment of advanced ADC biomarker of tumor cellularity, now in clinical testing, will be performed using sodium MRI. Additionally, imaging of bound sodium is included to facilitate the differentiation of edema from cell disintegration during tumor therapy. Sodium MRI applied to oncology will be evaluated for future translation to high field clinical MR scanners.