Parahydrogen-Hyperpolarized Propane-d6 Gas Contrast Agent: T1 Relaxation Dynamics and Pilot Millimeter-Scale Ventilation MRI.

Abstract

Hyperpolarized (HP) MRI provides enhanced signals over conventional MRI due to the increase in nuclear spin polarization by orders of magnitude compared to thermal polarization. Therefore, HP MRI can be successfully utilized toward imaging of low-density gases in void spaces, such as human lungs. Specifically, in clinical pulmonary imaging, HP MRI employs a gaseous contrast agent that fills the lungs during inhalation under physiologically relevant conditions prior to imaging. FDA-approved HP ¹²⁹Xe gas can now be used as the first HP inhalable gaseous contrast agent for functional lung imaging in adults and pediatric patients above 12 years for diagnosis and monitoring responses to the treatment of many pulmonary diseases. However, despite the substantial success of HP ¹²⁹Xe in research settings, the production and MRI of this novel contrast agent remain expensive and not universally available on clinical MRI scanners. An alternative approach is to deploy a proton-hyperpolarized gas that is cheap and fast to produce and can be detected on any clinical MRI scanner without any modification. Hyperpolarized propane gas has recently emerged as a potential next-generation hyperpolarized inhalable contrast agent. Here, the relaxation dynamics of two deuterated hyperpolarized propane isotopologues have been explored at clinically relevant conditions of 1 atm gas pressure and 0.35 and 1.4 T magnetic fields using pairwise addition of parahydrogen to a corresponding unsaturated precursor over the heterogeneous Rh/TiO₂ catalyst. The T₁ relaxation time of HP propane-d₆ gas (0.91±0.03 s) at 1.4 T was found to be similar to that of HP propane gas (0.81±0.06 s) because the dominating relaxation mechanism is due to the coupling of the nuclear spins to the molecular rotation of these two propane gas isotopologues. Moreover, the effective polarization decay constant increases for HP propane-d₆ to 1.35±0.05 s (and for HP propane to 1.35±0.10 s) at 0.35 T, pointing to the likely "partial" presence of the long-lived spin states (LLSS) at this clinically relevant field, corresponding to the intermediate spin-spin coupling regime of the two parahydrogen-derived hyperpolarized sites. Furthermore, the pilot feasibility of rapid lung ventilation imaging with 1 × 1 × 9 mm² voxel-size spatial resolution using a clinical 0.35 T open MRI scanner was demonstrated by inflating HP propane-d₆ gas in excised rabbit lungs, despite the reduction of the HP gas relaxation constant to 0.78 ± 0.02 s in the lungs.