Combining hyperpolarized ¹²⁹Xe MR imaging and spectroscopy to noninvasively estimate pulmonary vascular resistance

Hyperpolarized ¹²⁹Xe MRI/MRS enables quantitative mapping of function in lung airspaces, membrane tissue, and red blood cells (RBCs) within the pulmonary capillaries. The RBC signal also exhibits cardiogenic oscillations that are reduced in precapillary pulmonary hypertension (PH). This effect is obscured in patients with concomitant defects in transfer from airspaces to RBCs, which increase RBC oscillation amplitudes. Here, we provide a framework for interpreting RBC oscillations and show their relationship to pulsatile blood flow, capillary blood volume, capillary compliance, and impedance of the capillary and venous circulation. This framework was first applied to characterize RBC oscillations in a cohort of subjects with pulmonary disease but no known PH (n = 129). ¹²⁹Xe MRI of RBC transfer was used to estimate capillary blood volume, and as it decreased, RBC oscillations sharply increased ([Formula: see text] = 0.53), consistent with model predictions. Model-derived fit parameters were then used to estimate the distribution of pulmonary vascular resistance (PVR) across arterial, capillary, and venous circulation and to correct oscillations for RBC transfer defects. Seventy percent of PVR was estimated to arise from pulmonary arteries, 11% from capillaries, and 19% from veins. When tested in a second cohort of subjects who underwent ¹²⁹Xe MRI/MRS and right heart catheterization (n = 40), oscillations corrected for capillary blood volume correlated moderately with PVR (r² = 0.27, P = 0.0014). For every 1.96 Wood units (WU) increase in PVR, corrected oscillations decreased by 1 absolute percentage point. This work demonstrates that, although ¹²⁹Xe-RBC oscillations are only indirectly sensitive to precapillary obstruction, corrected oscillations below 7.5% were 100% specific for elevated PVR.NEW & NOTEWORTHY Cardiogenic oscillations in the ¹²⁹Xe red blood cell (RBC) resonance decrease in precapillary pulmonary hypertension (PH) but are enhanced when capillary blood volume is reduced. To separate these effects, we developed a physiological model that used ¹²⁹Xe gas exchange MRI to estimate blood volume, which was used to correct oscillation amplitude measurements. Corrected amplitudes correlated significantly with pulmonary vascular resistance, highlighting the potential for future noninvasive detection of PH.