The Protein and Contrast Agent–Specific Influence of Pathological Plasma-Protein Concentration Levels on Contrast-Enhanced Magnetic Resonance Imaging

Goetschi, Stefan; Froehlich, Johannes M.; Chuck, Natalie; Curcio, Raffaele; Runge, Val M.; Andreisek, Gustav; Nanz, Daniel; Boss, Andreas

doi:10.1097/rli.0000000000000061

Cited by 7 publications

(9 citation statements)

References 22 publications

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“…This may be due to the fact that the acidic environment can weaken the chelation of EGCG and Mn, thereby substantially accelerating the release of Mn 2þ . Furthermore, the difference in relaxivity may also be associated with the different experimental conditions used, as there are many factors that can influence relaxivity, including solvent type, incubation time, and even temperature (Hao et al, 2012;Goetschi et al, 2014). L-EGCG-Mn NPs also showed pH sensitivity in terms of shortening the T 2 relaxation time, which is similar to previous studies (Chen et al, 2012).…”

Section: Discussionsupporting

confidence: 75%

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent

Jiang

Shang

et al. 2020

Drug Delivery

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This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn 2þ nanoparticle (L-EGCG-Mn), a proof-of-concept pH-sensitive manganese core nanoparticle (NP), and compare its magnetic resonance (MR) properties with those of Gd-DTPA, both in vitro and in vivo. Reverse microemulsion was used to obtain the L-EGCG-Mn NPs. The physicochemical properties of L-EGCG-Mn were characterized using dynamic light scattering, transmission electron microscopy, and near-infrared fluorescence small animal live imaging. The in vitro relaxivity of L-EGCG-Mn incubated with different pH buffer solutions (pH ¼ 7.4, 6.8, 5.5) was evaluated. The T1-weighted MR imaging (MRI) properties were evaluated in vitro using hypoxic H22 cells as well as in H22 tumor-bearing mice. Cytotoxicity tests and histological analysis were performed to evaluate the safety of L-EGCG-Mn. L-EGCG-Mn showed good biocompatibility, stability, pH sensitivity, and tumor-targeting ability. Moreover, when the pH was decreased from 7.4 to 5.5, the r 1 relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM À1 Ás À1 . Furthermore, after incubation with L-EGCG-Mn for 4 h, the T1 relaxation time of hypoxic H22 cells was significantly lower than that of normoxic H22 cells (1788 ± 89 vs. 1982 ± 68 ms, p¼.041). The in vivo analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice (p < .05). Furthermore, L-EGCG-Mn was found to have a good safety profile via cytotoxicity tests and histological analysis. L-EGCG-Mn has a good safety profile and pH sensitivity and may thus serve as a potential MRI contrast agent.

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Section: Discussionsupporting

confidence: 75%

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent

Jiang

Shang

et al. 2020

Drug Delivery

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“…T1 relaxivity, known as r 1 , is influenced by many variables including magnetic field strength, temperature, environmental conditions, and protein concentration. 1,[3][4][5] Previous in vitro studies have examined the relative relaxivities of the Gd chelates. However, these have been incomplete (not including all relevant field strengths or deriving calculations from a wide range of concentrations), inapplicable to human imaging (not performed in human whole blood at physiologic temperatures), or failing to account for nonlinear 1/T1 vs [Gd] when proteins are present for the proteinbinding agents.…”

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confidence: 99%

T1 Relaxivities of Gadolinium-Based Magnetic Resonance Contrast Agents in Human Whole Blood at 1.5, 3, and 7 T

Shen

Goerner

Snyder

et al. 2015

Investigative Radiology

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OBJECTIVES Calculation of accurate T1 relaxivity (r1) values for gadolinium-based magnetic resonance contrast agents (GBCAs) is a complex process. As such, often referenced r1 values for the GBCAs at 1.5 T, 3 T, and 7 T are based on measurements obtained in media that are not clinically relevant, derived from only a small number of concentrations, or available for only a limited number of GBCAs. This study derives the r1 values of the 8 commercially available GBCAs in human whole blood at 1.5 T, 3 T, and 7 T. MATERIALS AND METHODS Eight GBCAs were serially diluted in human whole blood, at 7 concentrations from 0.0625 to 4 mM. A custom-built phantom held the dilutions in air-tight cylindrical tubes maintained at 37 ± 0.5°C by a heat-circulating system. Images were acquired using inversion recovery sequences with inversion times from 30 milliseconds to 10 seconds at 1.5 T and 3 T as well as 60 milliseconds to 5 seconds at 7 T. A custom MATLAB program was used to automate signal intensity measurements from the images acquired of the phantom. SigmaPlot was used to calculate T1 relaxation times and, finally, r1. RESULTS Measured r1 values in units of s[BULLET OPERATOR]mM at 1.5 T (3 T/7 T) were 3.9 ± 0.2 (3.4 ± 0.4/2.8 ± 0.4) for Gd-DOTA, 4.6 ± 0.2 (4.5 ± 0.3/4.2 ± 0.3) for Gd-DO3A-butrol, 4.3 ± 0.4 (3.8 ± 0.2/3.1 ± 0.4) for Gd-DTPA, 6.2 ± 0.5 (5.4 ± 0.3/4.7 ± 0.1) for Gd-BOPTA, 4.5 ± 0.1 (3.9 ± 0.2/3.7 ± 0.2) for Gd-DTPA-BMA, 4.4 ± 0.2 (4.2 ± 0.2/4.3 ± 0.2) for Gd-DTPA-BMEA, 7.2 ± 0.2 (5.5 ± 0.3/4.9 ± 0.1) for Gd-EOB-DTPA, and 4.4 ± 0.6 (3.5 ± 0.6/3.4 ± 0.1) for Gd-HP-DO3A. The agents can be stratified by relaxivity, with a significant additional dependency on field strength. CONCLUSIONS This report quantifies, for the first time, T1 relaxivity for all 8 gadolinium chelates in common clinical use worldwide, at current relevant field strengths, in human whole blood at physiological temperature (37°C). The measured r1 values differ to a small degree from previously published values, where such comparisons exist, with the current r1 measurements being that most relevant to clinical practice. The macrocyclic agents, with the exception of Gd-DO3A-butrol, have slightly lower r1 values when compared with the 2 much less stable linear agents, Gd-DTPA-BMA and Gd-DTPA-BMEA. The 2 agents with hepatobiliary excretion, Gd-EOB-DTPA and Gd-BOPTA, have, at 1.5 and 3 T, substantially higher r1 values than all other agents.

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“…Previously, the relaxivities of gadoxetate, gadobenate, and gadoterate were compared in different media: Rohrer et al [ 18 ] found that the relaxivity of gadobenate was similar to gadoxetate, and that these two contrast agents exhibited higher relaxivities than gadoterate in water, plasma, and blood with a T1-weighted TSE sequence at 1.5-T (blood) and 3-T (water, plasma) MRI. Moreover, Goetschi et al [ 19 ] found higher relaxivity of gadoxetate compared with gadoterate in saline. To compare our results to these studies, we focused on a specific contrast agent concentration of 0.25 mM which is most comparable to other literature reports.…”

Section: Discussionmentioning

confidence: 99%

Comparison of gadolinium-based contrast agents for MR cholangiography in saline, blood and bile: a phantom study

Froehlich¹,

Moussa

Guirguis

et al. 2023

Eur Radiol Exp

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Background We compared T1- and T2-weighted signal intensities of liver-specific (gadoxetate, gadobenate) and non-specific (gadoterate) gadolinium contrast agents (CAs) in a bile phantom. Methods In a phantom study, gadoxetate, gadobenate, and gadoterate were diluted in saline, blood, and bile at different concentrations (0, 0.25, 0.5. 1, 2.5, 5, 10, and 25 mM) and imaged in a 3-T magnetic resonance imaging (MRI) system using T1- and T2-weighted sequences. The maximum signal intensities of CAs were compared for each sequence separately and across all T1-weighted sequences using one-way ANOVA. Results Using T1-weighted sequences, CA concentration-dependent signal intensity increase was followed by decrease due to T2* effects. Comparing CAs for each sequence in bile yielded higher maximum signal intensities with gadobenate than gadoxetate and gadoterate using T1-weighted spin-echo (p < 0.010), multiecho gradient- and spin-echo (p < 0.001), and T1-weighted high-resolution isotropic volume excitation (eTHRIVE) sequences (p < 0.010). Comparing across all T1-weighted sequences in the bile phantom, gadobenate imaged using T1-weighted turbo field-echo (TFE) sequence showed the highest signal intensity, significantly higher than that using other CAs agents or sequences (p < 0.004) except for gadobenate and gadoxetate evaluated with three-dimensional multiecho fast field-echo (3D-mFFE) and gadoxetate with T1-weighted TFE sequence (p > 0.141). Signal reduction with CA concentration-dependent decrease was observed on T2-weighted images. Conclusion In this bile phantom study of gadolinium-based CA, gadobenate and gadoxetate showed high signal intensity with T1-weighted TFE and 3D-mFFE sequences, which supports their potential utility for contrast-enhanced hepatobiliary MRI. Key points • Contrast-enhanced magnetic resonance (MR) cholangiography depends on contrast agent type, kinetics, and concentration in bile, • We compared signal intensities of three contrast agents in a bile phantom study. • Gadobenate, gadoxetate, and gadoterate demonstrated different signal intensities at identical concentrations. • Gadoxetate and gadobenate showed high signal intensities on T1-weighted MR sequences.

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The Protein and Contrast Agent–Specific Influence of Pathological Plasma-Protein Concentration Levels on Contrast-Enhanced Magnetic Resonance Imaging

Cited by 7 publications

References 22 publications

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent

T1 Relaxivities of Gadolinium-Based Magnetic Resonance Contrast Agents in Human Whole Blood at 1.5, 3, and 7 T

Comparison of gadolinium-based contrast agents for MR cholangiography in saline, blood and bile: a phantom study

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