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中检测肿瘤反应的可靠性，该项目将评估一种双钠/质子生物标记物。需要检验的中心假设是，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，即这两种方法在可见的肿瘤缩小之前预测结果，相反，在无反应的肿瘤或无效治疗期间，这些反应不同。结合肿瘤细胞密度的指示剂ADC和钠核磁共振成像，可以同时通过癌细胞的两个相关的生理维度来评估肿瘤治疗。这一结果对于评估治疗效果以及因此加强对癌症患者的护理至关重要。对整个大脑的逐个像素的钠/ADC 2D分析将提供肿瘤对治疗的不同反应的量化地图。在大鼠胶质瘤模型中，TSC的变化可以发生在任何明显的肿瘤缩小之前一周，因此，钠核磁共振对评估肿瘤治疗结果具有预测能力，这一点将被研究。本项目将在9.4T的强磁场下对9L大鼠脑肿瘤的质子ADC和3DNa MRI的关系进行研究。该项目的第二个目标是评估ADC的肿瘤治疗，以及由钠结合决定的特定总钠池的变化，主要是与蛋白质的结合。化疗对脑肿瘤细胞的破坏减少了三量子钠信号(TQ)可以检测到的结合钠的量。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，以区分水肿性细胞反应和有效的肿瘤治疗。肿瘤治疗的评估将通过新的钠TQ信号检测来进行。创新包括能够最佳地检测范围广泛的钠结合，克服了TQ方法的主要缺点，即检测效率低和存在多个伪影。总而言之，目前正在进行临床测试的先进的ADC肿瘤细胞生物标志物的广泛评估将使用钠核磁共振进行。此外，还包括结合钠的成像，以便于在肿瘤治疗过程中区分水肿和细胞崩解。将对应用于肿瘤学的钠核磁共振进行评估，以便将来将其转化为高场强临床磁共振扫描仪。

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.