Sensitive Multichannel ¹⁹F Magnetic Resonance Imaging Enabled by Paramagnetic Fluorinated Ionic Liquid-Based Probes

Owing to its negligible biological background and high magnetic resonance sensitivity, ¹⁹F magnetic resonance imaging (MRI) has emerged as a competitive complement for ¹H MRI, which is already widely used in biomedical research and clinical practice. The performance of ¹⁹F MRI is greatly reliant on imaging probes, the development of which poses considerable demands on ¹⁹F sources. Fluorinated ionic liquids (FILs) have recently attracted increasing attention as alternative ¹⁹F sources because of their good aqueous solubility, ease of chemical modification, and high fluorine contents. However, the imaging performance of FIL-based probes is significantly restricted by their unfavorable ¹⁹F relaxation times. Herein, we developed a strategy to modulate the ¹⁹F relaxation times (including both T₁ and T₂) of FILs by exploiting the paramagnetic relaxation enhancement effect of Mn²⁺ ions to promote their imaging capacity. The ¹⁹F relaxation times of three FILs including EMIMBF₄, BMIMOTf, and BMIMPF₆ are appropriately tuned with paramagnetic Mn²⁺ ions at optimized concentrations, resulting in significant signal enhancement over 5-fold. We further utilized liposils to encapsulate these FILs with Mn²⁺ ions to construct ¹⁹F MRI probes, which enables fast and clear ¹⁹F MRI as illustrated by a series of in vivo experiments. Moreover, we made a ¹⁹F MRI probe containing all three FILs and Mn²⁺ ions at the optimized concentration, whose capacity for multiplexed ¹⁹F MRI is also validated with in vivo experiments. Our study demonstrates the promising potential of paramagnetic FIL-based probes for in vivo "hot spot" ¹⁹F MRI, and more importantly, the feasibility of relaxation modulation for the construction of high-performance ¹⁹F MRI probes.