Li Hua, Li Ke, Zhang Xiao-Yong, Jiang Xiaoyu, Zu Zhongliang, Zaiss Moritz, Gochberg Daniel F, Gore John C, Xu Junzhong
Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.
Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, USA.
NMR Biomed. 2015 Dec;28(12):1655-62. doi: 10.1002/nbm.3428. Epub 2015 Oct 14.
Amide proton transfer (APT) imaging may potentially detect mobile proteins/peptides non-invasively in vivo, but its specificity may be reduced by contamination from other confounding effects such as asymmetry of non-specific magnetization transfer (MT) effects and spin-lattice relaxation with rate R1 (=1/T1). Previously reported spillover, MT and R1 correction methods were based on a two-pool model, in which the existence of multiple water compartments with heterogeneous relaxation properties in real tissues was ignored. Such simple models may not adequately represent real tissues, and thus such corrections may be unreliable. The current study investigated the effectiveness and accuracy of correcting for R1 in APT imaging via simulations and in vivo experiments using tumor-bearing rats subjected to serial injections of Gd-DTPA that produced different tissue R1 values in regions of blood-brain-barrier breakdown. The results suggest that conventional measurements of APT contrast (such as APT* and MTRasym ) may be significantly contaminated by R1 variations, while the R1 -corrected metric AREX* was found to be relatively unaffected by R1 changes over a broad range (0.4-1 Hz). Our results confirm the importance of correcting for spin-lattice relaxation effects in quantitative APT imaging, and demonstrate the reliability of using the observed tissue R1 for corrections to obtain more specific and accurate measurements of APT contrast in vivo. The results also indicate that, due to relatively fast transcytolemmal water exchange, the influence of intra- and extracellular water compartments on CEST measurements with seconds long saturation time may be ignored in tumors.
酰胺质子转移（APT）成像有可能在体内无创地检测可移动的蛋白质/肽，但由于其他混杂效应的干扰，其特异性可能会降低，这些效应包括非特异性磁化转移（MT）效应的不对称性以及自旋晶格弛豫率R1（=1/T1）。先前报道的溢出、MT和R1校正方法基于双池模型，该模型忽略了真实组织中具有异质性弛豫特性的多个水腔室的存在。这种简单的模型可能无法充分代表真实组织，因此这种校正可能不可靠。本研究通过模拟和体内实验，研究了在血脑屏障破坏区域通过连续注射钆喷酸葡胺（Gd-DTPA）产生不同组织R1值的荷瘤大鼠，校正APT成像中R1的有效性和准确性。结果表明，传统的APT对比度测量（如APT和MTRasym）可能会受到R1变化的显著影响，而在较宽范围（0.4 - 1 Hz）内，经R1校正的指标AREX相对不受R1变化的影响。我们的结果证实了在定量APT成像中校正自旋晶格弛豫效应的重要性，并证明了使用观察到的组织R1进行校正以在体内获得更特异和准确的APT对比度测量的可靠性。结果还表明，由于跨细胞膜的水交换相对较快，在肿瘤中，细胞内和细胞外水腔室对饱和时间为秒级的化学交换饱和转移（CEST）测量的影响可能被忽略。
