Long-lived ¹⁵ N Hyperpolarization and Rapid Relaxation as a Potential Basis for Repeated First Pass Perfusion Imaging...

Deuteration of the exchangeable hydrogens of [¹⁵ N₂ ]urea was found to prolong the T₁ of the ¹⁵ N sites to more than 3 min at physiological temperatures. This significant increase in the lifetime of the hyperpolarized state of [¹⁵ N₂ ]urea, compared to [¹³ C]urea - a pre-clinically proven perfusion agent, makes [¹⁵ N₂ ]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 ¹⁵ N sites bound to labile protons and determining the hyperpolarized ¹⁵ N T₁ in H₂ O and D₂ O. Dissolution in D₂ O led to marked prolongation for all of the selected sites. In whole human blood, the T₁ of [¹⁵ N₂ ]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 [¹⁵ N₂ ]urea polarization prior to the contact with the blood is demonstrated using higher temperatures due to further T₁ prolongation.