Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Neuroimage. 2013 Aug 15;77:114-24. doi: 10.1016/j.neuroimage.2013.03.047. Epub 2013 Apr 6.
Chemical exchange saturation transfer (CEST) is a magnetization transfer (MT) technique to indirectly detect pools of exchangeable protons through the water signal. CEST MRI has focused predominantly on signals from exchangeable protons downfield (higher frequency) from water in the CEST spectrum. Low power radiofrequency (RF) pulses can slowly saturate protons with minimal interference of conventional semi-solid based MT contrast (MTC). When doing so, saturation-transfer signals are revealed upfield from water, which is the frequency range of non-exchangeable aliphatic and olefinic protons. The visibility of such signals indicates the presence of a relayed transfer mechanism to the water signal, while their finite width reflects that these signals are likely due to mobile solutes. It is shown here in protein phantoms and the human brain that these signals build up slower than conventional CEST, at a rate typical for intramolecular nuclear Overhauser enhancement (NOE) effects in mobile macromolecules such as proteins/peptides and lipids. These NOE-based saturation transfer signals show a pH dependence, suggesting that this process is the inverse of the well-known exchange-relayed NOEs in high resolution NMR protein studies, thus a relayed-NOE CEST process. When studying 6 normal volunteers with a low-power pulsed CEST approach, the relayed-NOE CEST effect was about twice as large as the CEST effects downfield and larger in white matter than gray matter. This NOE contrast upfield from water provides a way to study mobile macromolecules in tissue. First data on a tumor patient show reduction in both relayed NOE and CEST amide proton signals leading to an increase in magnetization transfer ratio asymmetry, providing insight into previously reported amide proton transfer (APT) effects in tumors.
化学交换饱和传递(CEST)是一种磁共振转移(MT)技术,通过水信号间接检测可交换质子的池。CEST MRI 主要集中在 CEST 谱中来自于水的低场(更高频率)可交换质子的信号上。低功率射频(RF)脉冲可以通过最小化常规半固态 MT 对比(MTC)的干扰来缓慢饱和质子。这样,从水的上方可以揭示饱和转移信号,这是不可交换脂肪族和烯烃质子的频率范围。这些信号的可见性表明存在向水信号的中继传递机制,而它们的有限宽度反映了这些信号可能是由于可移动溶质。在蛋白质模型和人脑上的实验结果表明,这些信号的积累速度比传统的 CEST 慢,其速率与蛋白质/肽和脂质等可移动大分子的分子内核奥弗豪瑟增强(NOE)效应典型速率相当。这些基于 NOE 的饱和转移信号表现出 pH 依赖性,这表明该过程是高分辨率 NMR 蛋白质研究中众所周知的交换中继 NOE 的逆过程,因此是一种中继-NOE CEST 过程。当使用低功率脉冲 CEST 方法研究 6 名正常志愿者时,中继-NOE CEST 效应比低场的 CEST 效应大两倍,且在白质中的效应比灰质大。这种来自于水的 NOE 对比可以提供一种研究组织中可移动大分子的方法。首例肿瘤患者的数据显示,中继 NOE 和 CEST 酰胺质子信号都减少,导致磁化转移率不对称性增加,为先前报道的肿瘤中酰胺质子转移(APT)效应提供了深入了解。