Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH

Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH
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DOI:
10.1088/0031-9155/59/16/4493
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发表时间:
2014-08-21
影响因子:
3.5
通讯作者:
Wu, Renhua
Wu, Renhua
中科院分区:
工程技术2区
文献类型:
--
作者:
Sun, Phillip Zhe;Longo, Dario Livio;Wu, Renhua

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pH敏感的化学交换饱和转移(CEST)MRI在体内应用方面具有很大的前景。然而,CEST效应不仅取决于交换速率,因此也取决于pH,还取决于造影剂浓度,其必须独立地确定以用于pH定量。比率CEST MRI通过比较多个不稳定质子的CEST测量值来标准化浓度效应,以简化pH测定。碘帕醇是一种常用的X射线造影剂,已被探索作为比率CEST试剂用于成像pH。然而,碘帕醇CEST特性尚未解决,其测定对于碘帕醇pH成像的优化和定量非常重要。我们的研究数值求解了碘帕醇多位点pH依赖性化学交换性质。我们发现,碘帕醇CEST MRI适用于测量pH值在6和7.5之间,尽管T-1和T-2测量值随pH值和浓度变化很大。pH MRI精度随pH和浓度的增加而降低。对于pH 6的40和20 mM碘帕醇溶液,从MRI测定的pH的标准偏差为0.2和0.4 pH单位,并且对于pH高于7,其改善为小于0.1单位。此外,我们确定了2-羟基丙酰胺基(k(sw)= 1.2*10(pH-4.1))和酰胺基(k(sw)= 1.2*10(pH-4.6))质子的碱催化化学交换,这两种质子之间存在统计学差异(P < 0.01,ANCOVA),对这一点的理解应有助于指导碘帕醇pH成像的体内转化。
pH-sensitive chemical exchange saturation transfer (CEST) MRI holds great promise for in vivo applications. However, the CEST effect depends on not only exchange rate and hence pH, but also on the contrast agent concentration, which must be determined independently for pH quantification. Ratiometric CEST MRI normalizes the concentration effect by comparing CEST measurements of multiple labile protons to simplify pH determination. Iopamidol, a commonly used x-ray contrast agent, has been explored as a ratiometric CEST agent for imaging pH. However, iopamidol CEST properties have not been solved, determination of which is important for optimization and quantification of iopamidol pH imaging. Our study numerically solved iopamidol multi-site pH-dependent chemical exchange properties. We found that iopamidol CEST MRI is suitable for measuring pH between 6 and 7.5 despite that T-1 and T-2 measurements varied substantially with pH and concentration. The pH MRI precision decreased with pH and concentration. The standard deviation of pH determined from MRI was 0.2 and 0.4 pH unit for 40 and 20 mM iopamidol solution of pH 6, and it improved to be less than 0.1 unit for pH above 7. Moreover, we determined base-catalyzed chemical exchange for 2-hydrooxypropanamido (k(sw) = 1.2*10(pH-4.1)) and amide (k(sw) = 1.2*10(pH-4.6)) protons that are statistically different from each other (P < 0.01, ANCOVA), understanding of which should help guide in vivo translation of iopamidol pH imaging.