Ultrafast scanning of exchangeable sites by NMR spectroscopy.
Ultrafast scanning of exchangeable sites by NMR spectroscopy.
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通过核磁共振波谱法对可交换位点进行超快扫描。
DOI：
10.1002/anie.201303255
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Jerschow,Alexej
中科院分区：
文献类型：
--
作者：
Xu,Xiang;Lee,Jae-Seung;Jerschow,Alexej
化学交换饱和转移 (CEST) 和磁化转移 (MT) 已成为广泛流行的用于在体内和体外生成增强 MRI 对比度的技术。 [1]为了充分表征这些现象并研究合适的造影剂候选者，测量报告信号（通常是水）的偏振作为饱和射频（RF）辐射（Z 谱）的频率偏移的函数。 [2]在这里，我们提出了一种超快方法，只需从两个信号激励即可获得大范围频率偏移的 Z 谱。该方法可用于在不同实验条件（例如饱和时间和功率）下快速筛选成像模型以及顺磁性和抗磁性化学交换饱和转移（CEST）造影剂。 CEST 为以下生物标志物、[3] 代谢物、[4] 和酶 [5] 提供了前景，因为它们参与组织和体内的代谢。许多内源性和外源性分子已被鉴定用于产生对比，这是基于质子从分子环境到大量水池的交换。内源性对比的例子包括测量酰胺质子转移 (APT)、[3] 糖原 (GlyCEST)、[6] 糖胺聚糖 (gagCEST)、[7] 谷氨酸 (GluCEST)、[8] 和葡萄糖 (GlucoCEST)[9]，这对于帮助骨关节炎和中风等疾病的诊断和随访非常重要。外源性 CEST 制剂领域主要是具有可交换质子位点的顺磁位移剂 (paraCEST) 的开发。 [10]原则上，由于涉及大的频率偏移，这些可以允许高功率照射。 ParaCEST 试剂已用于温度和 pH 绘图、[11] 靶向细胞、[12] 和检测酶活性。 [13]还开发了抗磁性 CEST (diaCEST) 试剂，例如多肽和报告基因。 [14]最近，也有报道使用超极化气体作为 CEST 生物传感器。 [15] 该方法只需两次扫描即可获得完整的 Z 光谱，并且还可以与基于同时成像多个样本的其他高通量方法相结合，[16] 以及使用自动采样器。这里介绍的 Z 光谱的一次性采集受到“超快”NMR 光谱方法的启发，[17] 此后称为超快 Z 光谱（UFZ 光谱）。超快 NMR 方法通常使用间接演化时间的空间编码来加速多维 NMR 实验。因此，2D和3D超快NMR实验已经得到证明，并且该原理也已应用于MRI方法学中。 [18]提出了一种用于宽带激励和获取 MT 效应的一次性方法，[19]，但从未在 CEST 背景下使用。 UFZ 的脉冲序列如图 1a 所示。在第一个梯度脉冲期间，距梯度中心距离 d 处的样本部分感受到额外的外部场，其总计为 ΔBsat (d)= Gsat d，这使该切片中的所有共振偏移 Δωsat (d)= γGsat d，其中 γ 是质子的旋磁比，Gsat 是梯度脉冲的强度。饱和射频辐射始终保持在零偏移频率，因此切片在偏移 ΔΔωsat (d) 处经历有效的共振辐射。在采集期间，梯度 Gacq（不需要具有相同的强度）产生 Δωacq (d)= γGacq d 的偏移。然后绘制所采集信号的傅里叶变换频谱与 Δωacq (d) 的关系图，该频谱与
Chemical exchange saturation transfer (CEST) and magnetization transfer (MT) have become widely popular techniques for generating enhanced MRI contrast in vivo and ex vivo.[1] To fully characterize these phenomena and to investigate suitable candidates for contrast agents, the polarization of the reporter signal (typically water) is measured as a function of the frequency offset of the saturating radio-frequency (RF) irradiation (Z-spectrum).[2] Here, we present an ultrafast method to obtain a Z-spectrum over a large range of frequency offsets from only two signal excitations. This method can be useful for fast screening of imaging phantoms and para-and diamagnetic chemical exchange saturation transfer (CEST) contrast agents under different experimental conditions (eg saturation time and power). CEST offers the prospect of following biomarkers,[3] metabolites,[4] and enzymes [5] as they participate in the metabolism in tissues and in vivo. Many endogenous as well as exogenous molecules have been identified for the generation of contrast that is based on the exchange of protons from the molecular environment to a bulk water pool. Examples of endogenous contrast include the measurement of the amide proton transfer (APT),[3] glycogen (GlyCEST),[6] glycosaminoglycan (gagCEST),[7] glutamate (GluCEST),[8] and glucose (GlucoCEST)[9], which can become important for helping in the diagnosis and followup of diseases such as osteoarthritis and stroke. The field of exogenous CEST agents is dominated by the development of paramagnetic shift agents (paraCEST) with exchangeable proton sites.[10] These can, in principle, allow for high-power irradiation because of the large frequency offsets involved. ParaCEST agents have been used for temperature and pH mapping,[11] targeting cells,[12] and detecting enzyme activities.[13] Diamagnetic CEST (diaCEST) agents, such as polypeptides and reporter genes have also been developed.[14] Recently, the use of hyperpolarized gas as CEST biosensors has also been reported.[15]The proposed method acquires full Z-spectra in only two scans, and could also be combined with additional highthroughput approaches based on imaging multiple samples simultaneously,[16] as well as with the use of auto-samplers. The one-shot acquisition of a Z-spectrum presented here is inspired by “ultrafast” NMR spectroscopic methods,[17] henceforth called ultrafast Z-spectroscopy (UFZ spectroscopy). Ultrafast NMR methods typically use spatial encoding of indirect evolution times to speed up multi-dimensional NMR experiments. Thus 2D and 3D ultrafast NMR experiments have been demonstrated, and the principle has also been applied to MRI methodology.[18] A one-shot method was proposed for the broadband excitation and acquisition of MT effects,[19] but was never used in the context of CEST. The pulse sequence for UFZ is shown in Figure1a. During the first gradient pulse, a portion of a sample at a distance d from the center of the gradient feels an additional external field amounting to ΔBsat (d)= Gsat d, which shifts all resonances in this slice by Δωsat (d)= γGsat d, where γ is the gyromagnetic ratio of a proton and Gsat is the strength of the gradient pulse. The saturating RF irradiation is held at the zero offset frequency throughout, hence the slice experiences an effective irradiation of resonances at an offset ÀΔωsat (d). During acquisition, the gradient Gacq (which needs not be of the same strength) produces a shift by Δωacq (d)= γGacq d. The Fourier-transformed spectrum of the acquired signal is then plotted versus Δωacq (d), which is related to the
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辐射阻尼对 Z 谱的影响。
DOI：
--
发表时间：
2006
期刊：
Journal of magnetic resonance (San Diego, Calif. 1997 : Print)
影响因子：
--
作者：
D. C. Williamson;J. Närväinen;P. Hubbard;R. Kauppinen;G. Morris
通讯作者：
G. Morris
影响因子：
15
作者：
Zhang, SR;Trokowski, R;Sherry, AD
通讯作者：
Sherry, AD
交叉弛豫核磁共振谱的宽带激发和检测
影响因子：
2.2
作者：
S. Swanson
通讯作者：
S. Swanson
影响因子：
--
作者：
Liu, Guanshu;Gilad, Assaf A.;Bulte, Jeff W. M.;van Zijl, Peter C. M.;McMahon, Michael T.
通讯作者：
McMahon, Michael T.
影响因子：
2.2
作者：
Lee, Jae-Seung;Regatte, Ravinder R.;Jerschow, Alexej
通讯作者：
Jerschow, Alexej