Multi-Field Relaxation Dynamics of Parahydrogen-Hyperpolarized Propane Gas MRI Contrast Agent

Abstract

Abstract Hyperpolarized gas-phase MRI is an emerging diagnostic modality, with the clinical utility of hyperpolarized Xe-129 gas for functional lung imaging recently supported by FDA regulatory approval. However, the requirement for dedicated multi-nuclear hardware and complex, centralized production logistics remains a significant translational hurdle. Here, we investigate the longitudinal relaxation dynamics of hyperpolarized propane gas─a promising, proton-frequency alternative produced via heterogeneous parahydrogen-induced polarization (HET-PHIP)─across a wide range of magnetic field strengths: 0.35 T, 0.55 T, 3 T, and 7 T MRI scanners. In the imaging studies, gradient-echo MRI pulse sequence variants with small flip angle excitation radio-frequency pulses were utilized to record a series of scans to monitor the effective decay of the hyperpolarized state of propane gas in spherical plastic phantoms and excised rabbit lungs. We demonstrate that the effective lifetime (characterized by the constant of a mono-exponential signal decay Td) of hyperpolarized propane is strongly field-dependent, exhibiting a marked decrease from 1.51 ± 0.04 s (0.35 T) to 0.59 ± 0.02 s (0.55 T) to 0.54 ± 0.02 s (3 T) to 0.23 ± 0.01 s (7 T) in phantom studies using an RF flip angle of 5°. This trend is attributed to the presence of partially retained long-lived spin states at the low field of 0.35 T, which are quenched at higher field strengths as the spin system transitions from the strong-coupling to the weak-coupling regime. Moreover, the unfavorable spin-rotation dominated relaxation results in a further decrease of Td at higher magnetic fields, especially evident at 7 T. Furthermore, we assess the relaxation behavior in excised rabbit lungs at 0.35 T, reporting a Td value of 0.68 ± 0.12 s. This accelerated relaxation of hyperpolarized propane in the lung compared to phantom models is likely driven by susceptibility-induced dephasing and increased surface-to-volume interactions within the alveolar architecture. The results using hyperpolarized propane were also compared with imaging studies using hyperpolarized Xe-129 gas in the excised rabbit lungs at 0.35 T, yielding an effective 129Xe T1 of 11 ± 2 s. These results provide a fundamental biophysical characterization of hyperpolarized propane and underscore its potential as a highly accessible contrast agent for regional pulmonary function mapping.