AbstractPurposeTo assess the regional amplitude and phase of dissolved 129Xe red blood cell (RBC) signal oscillations in the lung vasculature with keyhole spectroscopic imaging and to compare with previous methodology, which does not account for oscillation phase.Methods129Xe gas transfer was measured with a four‐echo 3D radial spectroscopic imaging sequence. Keyhole reconstruction‐based RBC signal oscillation amplitude mapping was applied retrospectively to data acquired from 28 healthy volunteers, 4 chronic thromboembolic pulmonary hypertension (CTEPH) patients, and 5 patients who were hospitalized due to COVID‐19 pneumonia and had residual lung abnormalities. Using a sliding window keyhole reconstruction, maps of RBC oscillation amplitude were corrected for regional phase difference. Repeatability of the phase‐adjusted oscillation amplitude was assessed in 8 healthy volunteers across three scans.ResultsWith sliding window keyhole reconstruction, regional phase differences were observed in the RBC signal oscillations: mean phase = (0.27 ± 0.19) rad in healthy volunteers, (0.24 ± 0.13) rad in CTEPH patients, and (0.33 ± 0.19) rad in patients with post‐COVID‐19 residual lung abnormality. The oscillation amplitude and phase maps were more heterogeneous (i.e., they showed increased coefficient of variation) for the CTEPH patients. The RBC oscillation amplitude was repeatable, and the mean three‐scan coefficient of variation was smaller when the phase adjustment was made (0.07 ± 0.04 compared with 0.16 ± 0.05).ConclusionSliding window keyhole reconstruction of radial dissolved 129Xe imaging reveals regional phase differences in the RBC oscillations, which are not captured when performing two phase keyhole reconstruction. This regional phase information may reflect the hemodynamic effect of the cardiac pulse wave in the pulmonary microvasculature.