Dual Sodium MRI and Proton ADC Assessment of Rodent Glioma Therapy

描述（由申请人提供）：为了提高在抗癌治疗过程中检测肿瘤反应的可靠性，本项目将评估一种双钠/质子生物标志物。待验证的中心假设认为，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，因此两种方法在可见肿瘤缩小之前预测结果，相反，这些反应在无反应肿瘤或无效治疗期间有所不同。ADC是肿瘤细胞的一种指标，与钠磁共振成像结合，可以同时从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，从而提高对癌症患者的护理至关重要。全脑逐像素钠/ADC 2D分析将提供肿瘤对治疗异质性反应性的定量图谱。在大鼠胶质瘤模型中，TSC的变化可以在任何明显的肿瘤缩小前一周发生，因此钠磁共振成像对评估肿瘤治疗结果具有预测能力，这将被研究。本项目将对9L大鼠脑肿瘤在9.4 T的高磁场下进行多次化疗，进行质子ADC与3D Na MRI的关系。该项目的第二个目标是评估ADC治疗肿瘤的效果，以及通过Na结合（主要与蛋白质结合）确定的特定总钠池的变化。化疗的脑肿瘤细胞破坏降低了结合钠的量，这是由三量子钠信号（TQ）检测。TQ Na信号的变化通常与SQ Na信号的变化方向相反。这一特征有望补充ADC分析，以区分水肿细胞反应和有效的肿瘤治疗。评估肿瘤治疗将进行新的钠TQ信号检测。创新包括对大范围Na结合的最佳检测能力，克服了TQ方法的主要缺点，即检测效率低和存在多个伪影。总之，目前处于临床试验阶段的肿瘤细胞高级ADC生物标志物的广泛评估将使用钠磁共振成像进行。此外，在肿瘤治疗过程中，结合钠的成像也包括在内，以促进水肿和细胞解体的区分。钠磁共振成像应用于肿瘤学将评估未来转化为高场临床磁共振扫描仪。

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.