Robust spectral averaging and chemical shift calculation for hyperpolarized ¹²⁹Xe MR spectroscopy

To establish methods for ¹²⁹Xe MRS quantification of the red blood cell to membrane signal ratio (RBC:M) and dissolved-phase chemical shifts that are optimized for repeatability.

The effects of cardiogenic RBC signal oscillations on RBC:M were simulated to determine the optimal FID averaging duration; variability was evaluated in healthy volunteers and idiopathic pulmonary fibrosis patients (n = 55). Dissolved-phase shifts were calculated in progressive pulmonary fibrosis patients (n = 114) using two 0-ppm references: the incidental gas resonance arising during dissolved-phase excitation and a dedicated gas-phase excitation. The repeatability of each method was compared, and that of the dedicated gas reference was assessed in subjects with various cardiopulmonary disorders (n = 155). Optimized methods were then used to re-evaluate published healthy reference values.

The variability of RBC:M measurements followed a sinc-like envelope with FID averaging duration, exhibiting minima at integer multiples of the cardiac period. Dissolved-phase shifts were most repeatable when referenced to the dedicated gas signal. Cardiac cycle averaging did not change the healthy reference RBC:M (0.49 ± 0.11, p = 0.75), but using the dedicated gas resonance increased healthy reference membrane and RBC shifts by 0.2 and 0.1 ppm to 197.8 ± 0.3 and 218.3 ± 0.5 ppm, respectively (p < 0.001). Membrane and RBC shifts demonstrated good repeatability coefficients of 0.32 and 0.52 ppm.

RBC:M is most repeatable when averaged over a cardiac cycle, although 1-s averaging yields similar performance. Dissolved-phase shifts are most repeatable using dedicated gas-phase excitations as the 0-ppm reference frequency.