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

Abstract

The hyperpolarization of nuclear spins has enabled real-time molecular magnetic resonance imaging. Hyperpolarized tracers like pyruvate have enabled visualization of real-time metabolism in vitro and in vivo. However, the scope of hyperpolarizable molecules remains limited. We found that specific molecules such as ¹⁵N-pyridine, 1-¹⁵N-nicotinamide, and ¹⁵N-nicotinic acid can be hyperpolarized well using dynamic nuclear polarization; however, the polarization does not persist after dissolution. The primary contribution to this swift relaxation is a rapid chemical exchange of protons and possibly other interactions, which accelerate relaxation at low magnetic fields. We discovered that adding molecules, nicotinamide, urea, nicotinic acid, and glycerol to the dissolution medium, protected the tracers from relaxation and dramatically improved ¹⁵N polarization. This chemically induced deceleration of nuclear spin relaxation (CIDER) effect allowed us to observe the highest ¹⁵N hyperpolarization reported in literature so far, almost 30% for the biomolecule 1-¹⁵N nicotinamide. We anticipate that CIDER will be very useful to prolong the T₁ of various molecules, thereby extending the scope and boundaries of hyperpolarization molecular imaging and beyond.