Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA.
NMR Biomed. 2014 Apr;27(4):406-16. doi: 10.1002/nbm.3075. Epub 2014 Jan 29.
Chemical exchange saturation transfer (CEST) provides an indirect means to detect exchangeable protons within tissues through their effects on the water signal. Previous studies have suggested that amide proton transfer (APT) imaging, a specific form of CEST, detects endogenous amide protons with a resonance frequency offset 3.5 ppm downfield from water, and thus may be sensitive to variations in mobile proteins/peptides in tumors. However, as CEST measurements are influenced by various confounding effects, such as spillover saturation, magnetization transfer (MT) and MT asymmetry, the mechanism or degree of increased APT signal in tumors is not certain. In addition to APT, nuclear Overhauser enhancement (NOE) effects upfield from water may also provide distinct information on tissue composition. In the current study, APT, NOE and several other MR parameters were measured and compared comprehensively in order to elucidate the origins of APT and NOE contrasts in tumors at 9.4 T. In addition to conventional CEST methods, a new intrinsic inverse metric was applied to correct for relaxation and other effects. After corrections for spillover, MT and T1 effects, corrected APT in tumors was found not to be significantly different from that in normal tissues, but corrected NOE effects in tumors showed significant decreases compared with those in normal tissues. Biochemical measurements verified that there was no significant enhancement of protein contents in the tumors studied, consistent with the corrected APT measurements and previous literature, whereas quantitative MT data showed decreases in the fractions of immobile macromolecules in tumors. Our results may assist in the better understanding of the contrast depicted by CEST imaging in tumors, and in the development of improved APT and NOE measurements for cancer imaging.
化学交换饱和传递（CEST）通过对水信号的影响，为检测组织内可交换质子提供了一种间接手段。先前的研究表明，酰胺质子转移（APT）成像，CEST 的一种特殊形式，检测到与水共振频率相差 3.5 ppm 下的内源性酰胺质子，因此可能对肿瘤中移动蛋白/肽的变化敏感。然而，由于 CEST 测量受到各种混杂效应的影响，如溢出饱和、磁化转移（MT）和 MT 不对称性，肿瘤中 APT 信号增加的机制或程度尚不确定。除了 APT，水上游离核 Overhauser 增强（NOE）效应也可能为组织成分提供独特的信息。在当前的研究中，全面测量和比较了 APT、NOE 和其他几种 MR 参数，以阐明在 9.4 T 下肿瘤中 APT 和 NOE 对比的起源。除了传统的 CEST 方法外，还应用了一种新的内在逆度量方法来校正弛豫和其他效应。校正溢出、MT 和 T1 效应后，发现肿瘤中的校正 APT 与正常组织没有显著差异，但与正常组织相比，肿瘤中的校正 NOE 效应显著降低。生化测量证实，在所研究的肿瘤中，蛋白质含量没有显著增加，与校正 APT 测量和先前的文献一致，而定量 MT 数据显示肿瘤中不可移动大分子的分数降低。我们的结果可能有助于更好地理解 CEST 成像在肿瘤中描绘的对比，并为癌症成像中改进的 APT 和 NOE 测量的发展提供帮助。
