A Facile NMR Method for Pre-MRI Evaluation of Trigger-Responsive T₁ Contrast Enhancement

There is a growing interest in developing paramagnetic nanoparticles as responsive magnetic resonance imaging (MRI) contrast agents, which feature switchable T₁ image contrast of water protons upon biochemical cues for better discerning diseases. However, performing an MRI is pragmatically limited by its cost and availability. Hence, a facile, routine method for measuring the T₁ contrast is highly desired in early-stage development. This work presents a single-point inversion recovery (IR) nuclear magnetic resonance (NMR) method that can rapidly evaluate T₁ contrast change by employing a single, optimized IR pulse sequence that minimizes water signal for "off-state" nanoparticles and allows for sensitively measuring the signal change with "switch-on" T₁ contrast. Using peptide-induced liposomal gadopentetic acid (Gd³⁺-DTPA) release and redox-sensitive manganese oxide (MnO₂) nanoparticles as a demonstration of generality, this method successfully evaluates the T₁ shortening of water protons caused by liposomal Gd³⁺-DTPA release and Mn²⁺ formation from MnO₂ reduction. Furthermore, the NMR measurement is highly correlated to T₁-weighted MRI scans, suggesting its feasibility to predict the MRI results at the same field strength. This NMR method can be a low-cost, time-saving alternative for pre-MRI evaluation for a diversity of responsive T₁ contrast systems.