Chemically induced deceleration of nuclear spin relaxation (CIDER) preserves hyperpolarization

Gadolinium-based contrast agents have revolutionized MRI by accelerating spin relaxation. Agents that decelerate relaxation, however, were hitherto unknown. Such agents would be of great interest, e.g., for metabolic imaging with hyperpolarized tracers (e.g., ¹⁵N-pyridine, [1,4-¹³C₂]succinate, [1-¹⁵N]nicotinamide), where precious polarization, sometimes completely, is lost, e.g., during the transfer from the polarizer to the scanner. Here, we report on a previously unreported effect where tracers' longitudinal and transverse relaxation rates in aqueous solution are substantially reduced by adding biocompatible molecules such as nicotinamide, urea, glycerol, or dendrons. The impact on longitudinal relaxation is particularly effective in low magnetic fields and near pKa where T₁ was tripled. The effect substantially reduces the polarization loss during transfer, so hitherto unsuitable, fast-relaxing molecules can be used now. This way, we achieved the highest reported ¹⁵N hyperpolarization of nearly 30% for [1-¹⁵N]nicotinamide. This chemically induced deceleration of nuclear spin relaxation (CIDER) effect was confirmed using magnetic-field-cycling experiments and has broad potential applications in hyperpolarized MR and beyond.