Woessner Donald E, Zhang Shanrong, Merritt Matthew E, Sherry A Dean
Rogers Magnetic Resonance Center, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Magn Reson Med. 2005 Apr;53(4):790-9. doi: 10.1002/mrm.20408.
Paramagnetic lanthanide complexes that display unusually slow water exchange between an inner sphere coordination site and bulk water may serve as a new class of MRI contrast agents with the use of chemical exchange saturation transfer (CEST) techniques. To aid in the design of paramagnetic CEST agents for reporting important biological indices in MRI measurements, we formulated a theoretical framework based on the modified Bloch equations that relates the chemical properties of a CEST agent (e.g., water exchange rates and bound water chemical shifts) and various NMR parameters (e.g., relaxation rates and applied B(1) field) to the measured CEST effect. Numerical solutions of this formulation for complex exchanging systems were readily obtained without algebraic manipulation or simplification. For paramagnetic CEST agents of the type used here, the CEST effect is relatively insensitive to the bound proton relaxation times, but requires a sufficiently large applied B(1) field to highly saturate the Ln(3+)-bound water protons. This in turn requires paramagnetic complexes with large Ln(3+)-bound water chemical shifts to avoid direct excitation of the exchanging bulk water protons. Although increasing the exchange rate of the bound protons enhances the CEST effect, this also causes exchange broadening and increases the B(1) required for saturation. For a given B(1), there is an optimal exchange rate that results in a maximal CEST effect. This numerical approach, which was formulated for a three-pool case, was incorporated into a MATLAB nonlinear least-square optimization routine, and the results were in excellent agreement with experimental Z-spectra obtained with an aqueous solution of a paramagnetic CEST agent containing two different types of bound protons (bound water and amide protons).
在内部球配位位点与本体水之间表现出异常缓慢水交换的顺磁性镧系元素配合物，可作为一类新型的磁共振成像（MRI）造影剂，用于化学交换饱和转移（CEST）技术。为了辅助设计用于在MRI测量中报告重要生物学指标的顺磁性CEST造影剂，我们基于修正的布洛赫方程建立了一个理论框架，该框架将CEST造影剂的化学性质（例如水交换速率和结合水化学位移）以及各种核磁共振（NMR）参数（例如弛豫速率和施加的B(1)场）与测量的CEST效应联系起来。对于复杂交换系统，该公式的数值解无需代数运算或简化即可轻松获得。对于此处使用的这类顺磁性CEST造影剂，CEST效应相对不依赖于结合质子的弛豫时间，但需要足够大的施加B(1)场才能使与Ln(3+)结合的水质子高度饱和。这反过来要求顺磁性配合物具有较大的与Ln(3+)结合的水化学位移，以避免直接激发交换的本体水质子。尽管增加结合质子的交换速率会增强CEST效应，但这也会导致交换展宽并增加饱和所需的B(1)场。对于给定的B(1)场，存在一个导致最大CEST效应的最佳交换速率。这种针对三池情况制定的数值方法被纳入MATLAB非线性最小二乘优化程序中，结果与使用含有两种不同类型结合质子（结合水和酰胺质子）的顺磁性CEST造影剂水溶液获得的实验Z谱非常吻合。
