Long-lived ¹⁵N Hyperpolarization and Rapid Relaxation as a Potential Basis for Repeated First Pass Perfusion Imaging – Marked Effects of Deuteration and Temperature

Deuteration of the exchangeable hydrogens of [¹⁵N₂]urea was found to prolong the T₁ of the ¹⁵N sites to more than 3 min at physiological temperatures. This significant increase in the lifetime of the hyperpolarized state of [¹⁵N₂]urea, compared to [¹³C]urea – a pre-clinically proven perfusion agent, makes [¹⁵N₂]urea a promising perfusion agent. The molecular parameters that may lead to this profound effect were assessed by investigating small molecules with different molecular structures containing ¹⁵N sites bound to labile protons and determining the hyperpolarized ¹⁵N T₁ in H₂O and D₂O. Dissolution in D₂O led to marked prolongation for all of the selected sites. In whole human blood, the T₁ of [¹⁵N₂]urea was shortened. We present a general strategy for exploiting the markedly longer T₁ outside the body and the quick decay in blood for performing multiple hyperpolarized perfusion measurements with a single hyperpolarized dose. Improved storage of the generated [¹⁵N₂]urea polarization prior to the contact with the blood is demonstrated using higher temperatures due to further T₁ prolongation.