Inducing Defects in ¹⁹F-Nanocrystals Provides Paramagnetic-free Relaxation Enhancement for Improved In Vivo Hotspot MRI

Paramagnetic relaxation enhancement (PRE) is the current strategy of choice for enhancing magnetic resonance imaging (MRI) contrast and for accelerating MRI acquisition schemes. Yet, debates regarding lanthanides' biocompatibility and PRE-effect on MRI signal quantification have raised the need for alternative strategies for relaxation enhancement. Herein, we show an approach for shortening the spin-lattice relaxation time (T₁) of fluoride-based nanocrystals (NCs) that are used for in vivo ¹⁹F-MRI, by inducing crystal defects in their solid-crystal core. By utilizing a phosphate-based rather than a carboxylate-based capping ligand for the synthesis of CaF₂ NCs, we were able to induce grain boundary defects in the NC lattice. The obtained defects led to a 10-fold shorter T₁ of the NCs' fluorides. Such paramagnetic-free relaxation enhancement of CaF₂ NCs, gained without affecting either their size or their colloidal characteristics, improved 4-fold the obtained ¹⁹F-MRI signal-to-noise ratio, allowing their use, in vivo, with enhanced hotspot MRI sensitivity.