Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany.
Magn Reson Med. 2022 May;87(5):2436-2452. doi: 10.1002/mrm.29133. Epub 2021 Dec 27.
In principle, non-invasive mapping of the intracellular pH (pH ) in vivo is possible using endogenous chemical exchange saturation transfer (CEST)-MRI of the amide and guanidyl signals. However, the application for cancer imaging is still impeded, as current state-of-the-art approaches do not allow for simultaneous compensation of concomitant effects that vary within tumors. In this study, we present a novel method for absolute pH mapping using endogenous CEST-MRI, which simultaneously compensates for concentration changes, superimposing CEST signals, magnetization transfer contrast, and spillover dilution.
Compensation of the concomitant effects was achieved by a ratiometric approach (i.e. the ratio of one CEST signal at different B ) in combination with the relaxation-compensated inverse magnetization transfer ratio MTR and a separate first-order polynomial-Lorentzian fit of the amide and guanidyl signals at 9.4 T. Calibration of pH values was accomplished using in vivo-like model suspensions from porcine brain lysates. Applicability of the presented method in vivo was demonstrated in n = 19 tumor-bearing mice.
In porcine brain lysates, measurement of pH was feasible over a broad range of physiologically relevant pH values of 6.2 to 8.0, while being independent of changes in concentration. A median pH of approximately 7.2 was found in the lesions of 19 tumor-bearing mice.
The presented method enables non-invasive mapping of absolute pH values in tumors using CEST-MRI, which was so far prevented by concomitant effects. Consequently, pre-clinical studies on pH changes in tumors are possible allowing the assessment of pH in vivo as a biomarker for cancer diagnosis or treatment monitoring.
原则上，通过酰胺和胍基信号的内源性化学交换饱和传递（CEST）-MRI，可以实现体内细胞内 pH（pH）的无创映射。然而，由于当前的最新方法不能同时补偿肿瘤内变化的伴随效应，因此癌症成像的应用仍然受到阻碍。在这项研究中，我们提出了一种使用内源性 CEST-MRI 进行绝对 pH 映射的新方法，该方法可以同时补偿浓度变化、叠加 CEST 信号、磁化转移对比和溢出稀释。
通过比率法（即在不同 B 下一个 CEST 信号的比值）结合弛豫补偿的反磁化转移比 MTR，以及酰胺和胍基信号在 9.4 T 下的单独一阶多项式洛伦兹拟合，实现了伴随效应的补偿。pH 值的校准是使用来自猪脑匀浆的类似于体内的模型悬浮液完成的。在 n = 19 只荷瘤小鼠中证明了所提出方法的体内适用性。
在猪脑匀浆中，在生理相关的 pH 值 6.2 到 8.0 的广泛范围内，可以进行 pH 值的测量，而与浓度变化无关。在 19 只荷瘤小鼠的病变中发现 pH 值约为 7.2。
所提出的方法可以使用 CEST-MRI 无创地映射肿瘤中的绝对 pH 值，而这一方法迄今为止受到伴随效应的阻碍。因此，可以进行 pH 值变化的临床前研究，将 pH 值作为癌症诊断或治疗监测的生物标志物进行评估。
