Goetschi Stefan, Froehlich Johannes M, Chuck Natalie C, Curcio Raffaele, Runge Val M, Andreisek Gustav, Nanz Daniel, Boss Andreas
From the *Institute for Diagnostic and Interventional Radiology, University Hospital Zürich; †Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETHZ; and ‡Institute of Clinical Chemistry, University Hospital Zürich, Zürich, Switzerland.
Invest Radiol. 2014 Sep;49(9):608-19. doi: 10.1097/RLI.0000000000000061.
The objective of this study was to measure the protein-specific response of r1 and r2 relaxivities of commercially available gadolinium-based magnetic resonance imaging contrast agents to variation of plasma-protein concentrations.
In this in vitro study, contrast agent (gadofosveset trisodium, gadoxetate disodium, gadobutrol, and gadoterate meglumine) dilution series (0-2.5 mmol Gd/L) were prepared with plasma-protein (human serum albumin [HSA] and immunoglobulin G [IgG]) concentrations at physiological (42 and 10 g/L HSA and IgG, respectively, Normal) and at 3 pathological levels with HSA/IgG concentrations of 10/10 (solution Alb low), 42/50 (IgG mild), and 42/70 (IgG severe) g/L. Contrast-agent molar relaxivities and relaxivity-enhancing protein-contrast-agent interaction coefficients were determined on the basis of inversion-recovery and spin-echo data acquired at 1.5 and 3.0 T at 37°C. Protein-induced magnetic resonance imaging signal changes were calculated.
The effective r1 and r2 molar relaxivities consistently increased with albumin and IgG concentrations. At 1.5 T, the r1 values increased by 10.2 (gadofosveset), 4.3 (gadoxetate), 1.3 (gadobutrol), and 1.1 L s mmol (gadoterate), respectively, from the Alb low to the IgG severe solution. At 3.0 T, the r1 values increased by 2.9 (gadofosveset), 2.3 (gadoxetate), 0.7 (gadobutrol), and 0.9 (gadoterate) L s mmol, respectively. An excess of IgG most strongly increased the r1 of gadoxetate (+40 and +19% at 1.5 and 3.0 T, respectively, from Normal to IgG severe). An albumin deficiency most strongly decreased the r1 of gadofosveset (-44% and -20% at 1.5 and 3.0 T, respectively, from Normal to Alb low). The modeling confirmed a strong gadofosveset r1 enhancement by albumin and suggested stronger IgG than albumin effects on the apparent molar relaxivity of the other agents per protein mass concentration at 1.5 T.
Pathological deviations from normal plasma-protein concentrations in aqueous solutions result in changes of effective r1 and r2 contrast-agent relaxivities and projected signal enhancements that depend on the contrast agent, the blood-serum protein profile, and the field strength.
本研究的目的是测量市售钆基磁共振成像造影剂的r1和r2弛豫率对血浆蛋白浓度变化的蛋白质特异性反应。
在这项体外研究中，制备了造影剂（钆布醇三钠、钆塞酸二钠、钆贝葡胺和钆喷酸葡胺）稀释系列（0 - 2.5 mmol Gd/L），其血浆蛋白（人血清白蛋白 [HSA] 和免疫球蛋白G [IgG]）浓度处于生理水平（HSA和IgG分别为42和10 g/L，正常）以及3个病理水平，HSA/IgG浓度分别为10/10（白蛋白低溶液）、42/50（IgG轻度）和42/70（IgG重度）g/L。基于在37°C下1.5和3.0 T采集的反转恢复和自旋回波数据，测定造影剂的摩尔弛豫率和增强弛豫率的蛋白质 - 造影剂相互作用系数。计算蛋白质诱导的磁共振成像信号变化。
有效的r1和r2摩尔弛豫率随白蛋白和IgG浓度持续增加。在1.5 T时，从白蛋白低溶液到IgG重度溶液，r1值分别增加了10.2（钆布醇三钠）、4.3（钆塞酸二钠）、1.3（钆贝葡胺）和1.1 L·s/mmol（钆喷酸葡胺）。在3.0 T时，r1值分别增加了2.9（钆布醇三钠）、2.3（钆塞酸二钠）、0.7（钆贝葡胺）和0.9（钆喷酸葡胺）L·s/mmol。过量的IgG最强烈地增加了钆塞酸二钠的r1（在1.5和3.0 T时，从正常到IgG重度分别增加40%和19%）。白蛋白缺乏最强烈地降低了钆布醇三钠的r1（在1.5和3.0 T时，从正常到白蛋白低溶液分别降低44%和20%）。模型证实白蛋白对钆布醇三钠的r1有强烈增强作用，并表明在1.5 T时，每单位蛋白质质量浓度下，IgG对其他造影剂表观摩尔弛豫率的影响比白蛋白更强。
水溶液中血浆蛋白浓度与正常情况的病理偏差会导致有效r1和r2造影剂弛豫率以及预计信号增强的变化，这些变化取决于造影剂、血清蛋白谱和场强。
