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

AbstractThere 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.