The protein and contrast agent-specific influence of pathological plasma-protein concentration levels on contrast-enhanced magnetic resonance imaging.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
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.
Stefan
S
Goetschi
Johannes M
JM
Froehlich
Natalie C
NC
Chuck
Raffaele
R
Curcio
Val M
VM
Runge
Gustav
G
Andreisek
Daniel
D
Nanz
Andreas
A
Boss
D001798:Blood Proteins / Q000032:analysis*; D003287:Contrast Media; D005682:Gadolinium; D019786:Gadolinium DTPA; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008536:Meglumine; D009942:Organometallic Compounds; D011506:Proteins
D001798:Blood Proteins; D003287:Contrast Media; D009942:Organometallic Compounds; D011506:Proteins; C073590:gadolinium ethoxybenzyl DTPA; C090600:gadobutrol; D008536:Meglumine; D005682:Gadolinium; D019786:Gadolinium DTPA; C072417:gadoterate meglumine; C109932:gadofosveset trisodium