Optimized quantitative mapping of cardiopulmonary oscillations using hyperpolarized 129Xe gas exchange MRI: Digital phantoms and clinical evaluation in CTEPH

Purpose: The interaction between Xe-129 atoms and pulmonary capillary red blood cells provides cardiogenic signal oscillations that display sensitivity to precapillary and postcapillary pulmonary hypertension. Recently, such oscillations have been spatially mapped, but little is known about optimal reconstruction or sensitivity to artifacts. In this study, we use digital phantom simulations to specifically optimize keyhole reconstruction for oscillation imaging. We then use this optimized method to re-establish healthy reference values and quantitatively evaluate microvascular flow changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary thromboendarterectomy (PTE).Methods: A six-zone digital lung phantom was designed to investigate the effects of radial views, key radius, and SNR. One-point Dixon Xe-129 gas exchange MRI images were acquired in a healthy cohort (n = 17) to generate a reference distribution and thresholds for mapping red blood cell oscillations. These thresholds were applied to 10 CTEPH participants, with 6 rescanned following PTE.Results: For undersampled acquisitions, a key radius of 0.14k(max) was found to optimally resolve oscillation defects while minimizing excessive heterogeneity. CTEPH participants at baseline showed higher oscillation defect + low (32 +/- 14%) compared with healthy volunteers (18 +/- 12%, p < 0.001). For those scanned both before and after PTE, oscillation defect + low decreased from 37 +/- 13% to 23 +/- 14% (p = 0.03).Conclusions: Digital phantom simulations have informed an optimized keyhole reconstruction technique for gas exchange images acquired with standard 1-point Dixon parameters. Our proposed methodology enables more robust quantitative mapping of cardiogenic oscillations, potentially facilitating effective regional quantification of microvascular flow impairment in patients with pulmonary vascular diseases such as CTEPH.