Changes in the relaxivity of water-organic solvent miscible systems: Hidden forces beyond metal ions

The relaxivity of magnetic resonance imaging (MRI) contrast agents is primarily attributed to metal ions such as gadolinium (Gd) and iron. However, the impact of organic solutes on relaxivity, particularly through alterations in water molecule dynamics, has not been thoroughly investigated. This research was aimed to explore how organic solutes affect the relaxivities of water and Gd-based contrast agents (GBCAs), potentially revealing new aspects for the development of contrast agents.

To investigate the effects of different proportions of water-soluble organic solvents mixed with pure water and GBCA on T₁ and T₂ relaxivities.

Ethanol, dimethyl sulfoxide (DMSO), 1,4-dioxane, glycerin, ethylene glycol, diethylene glycol, polyethylene glycol (PEG) 200, and PEG 400 were mixed with ultrapure water in various ratios (100:0, 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80, 10:90, 0:100). GBCA was added to these mixtures at a concentration of 0.05 mmol/L. The mixtures underwent T₁ and T₂ mapping scans using a 3.0 Tesla MRI machine, and the relaxivities R₁ (1/T₁) and R₂ (1/T₂) were calculated and compared.

The relaxivity R₁ of ethanol, 1,4-dioxane, and DMSO mixtures with water or GBCA, as well as R₂ of DMSO mixtures with GBCA, initially increased and then decreased. Conversely, R₁ and R₂ increased significantly with higher proportions of diethylene glycol, PEG 200, and glycerin in the mixtures with GBCA. The increase in relaxivity R₁ was correlated with greater viscosity. When the proportion of DMSO and diethylene glycol exceeded 20%, minimal variability in R₂ was observed as the water content decreased.

Adding organic solvents to water and paramagnetic relaxation reagents could alter T₁ and T₂ relaxivities, suggesting potential new directions for modifying current contrast agents. Additionally, increasing the viscosity of the contrast agent was found to enhance the relaxivity.