Relaxation Dynamics of Nuclear Long-Lived Spin States in Propane and Propane-<i>d</i><sub>6</sub> Hyperpolarized by Parahydrogen (2019)

We report a systematic study of relaxation dynamics of hyperpolarized (HP) propane and HP propane-d<sub>6</sub> prepared by heterogeneous pairwise parahydrogen addition to propylene and propylene-d<sub>6</sub> respectively. Long-lived spin states (LLS) created for these molecules at the low magnetic field of 0.0475 T were employed for this study. The parahydrogen-induced overpopulation of a HP propane LLS decays exponentially with time constant (T<sub>LLS</sub>) approximately 3-fold greater than the corresponding T<sub>1</sub> values. Both T<sub>LLS</sub> and T<sub>1</sub> increase linearly with propane pressure in the range from 1 atm (the most biomedically relevant conditions for pulmonary MRI) to 5 atm. The T<sub>LLS</sub> value of HP propane gas at 1 atm is ~3 s. Deuteration of the substrate (propylene-d<sub>6</sub>) yields hyperpolarized propane-d<sub>6</sub> gas with T<sub>LLS</sub> values approximately 20% shorter than those of hyperpolarized fully protonated propane gas, indicating that deuteration does not benefit the lifetime of the LLS HP state. The use of pH<sub>2</sub> or Xe/N<sub>2</sub> buffering gas during heterogeneous hydrogenation reaction (leading to production of 100% HP propane (no buffering gas) versus 43% HP propane gas (with 57% buffering gas) composition mixtures) results in (i) no significant changes in T<sub>1</sub>, (ii) decrease of T<sub>LLS</sub> values (by 35±7% and 8±7% respectively); and (iii) an increase of the polarization levels of HP propane gas with a propane concentration decrease (by 1.6±0.1-fold and 1.4±0.1-fold respectively despite the decrease in T<sub>LLS</sub>, which leads to disproportionately greater polarization losses during HP gas transport). Moreover, we demonstrate the feasibility of HP propane cryo-collection (which can be potentially useful for preparing larger amounts of concentrated HP propane, when buffering gas is employed), and T<sub>LLS</sub> of liquefied HP propane reaches 14.7 seconds, which is greater than the T<sub>LLS</sub> value of HP propane gas at any pressure studied. Finally, we have explored the utility of using a partial Spin-Lock Induced Crossing (SLIC) radio frequency (RF) pulse sequence for converting the overpopulated LLS into observable <sup>1</sup>H nuclear magnetization at low magnetic field. We find that (i) the bulk of the overpopulated LLS is retained even when the optimal or near-optimal values of SLIC pulse duration are employed, and (ii) the overpopulated LLS of propane is also relatively immune to strong RF pulses-thereby, indicating that LLS is highly suitable as a spin-polarization reservoir in the context of NMR/MRI detection applications. The presented findings may be useful for improving the levels of polarization of HP propane produced by HET-PHIP via the use of an inert buffer gas; increasing the lifetime of the HP state during preparation and storage; and developing efficient approaches for ultrafast MR imaging of HP propane in the context of biomedical applications of HP propane gas, including its potential use as an inhalable contrast agent.