Using hyperpolarized ¹²⁹Xe gas-exchange MRI to model the regional airspace, membrane, and capillary contributions to...

Hyperpolarized ¹²⁹Xe MRI has emerged as a novel means to evaluate pulmonary function via 3D mapping of ventilation, interstitial barrier uptake, and RBC transfer. However, the physiological interpretation of these measurements has yet to be firmly established. Here, we propose a model that uses the three components of ¹²⁹Xe gas-exchange MRI to estimate accessible alveolar volume (V_A), membrane conductance, and capillary blood volume contributions to DL_CO. ¹²⁹Xe ventilated volume (VV) was related to V_A by a scaling factor k_V = 1.47 with 95% confidence interval [1.42, 1.52], relative ¹²⁹Xe barrier uptake (normalized by the healthy reference value) was used to estimate the membrane-specific conductance coefficient k_B = 10.6 [8.6, 13.6] mL/min/mmHg/L, whereas normalized RBC transfer was used to calculate the capillary blood volume-specific conductance coefficient k_R = 13.6 [11.4, 16.7] mL/min/mmHg/L. In this way, the barrier and RBC transfer per unit volume determined the transfer coefficient K_CO, which was then multiplied by image-estimated V_A to obtain DL_CO. The model was built on a cohort of 41 healthy subjects and 101 patients with pulmonary disorders. The resulting ¹²⁹Xe-derived DL_CO correlated strongly (R² = 0.75, P < 0.001) with the measured values, a finding that was preserved within each individual disease cohort. The ability to use ¹²⁹Xe MRI measures of ventilation, barrier uptake, and RBC transfer to estimate each of the underlying constituents of DL_CO clarifies the interpretation of these images while enabling their use to monitor these aspects of gas exchange independently and regionally.NEW & NOTEWORTHY The diffusing capacity for carbon monoxide (DL_CO) is perhaps one of the most comprehensive physiological measures used in pulmonary medicine. Here, we spatially resolve and estimate its key components-accessible alveolar volume, membrane, and capillary blood volume conductances-using hyperpolarized ¹²⁹Xe MRI of ventilation, interstitial barrier uptake, and red blood cell transfer. This image-derived DL_CO correlates strongly with measured values in 142 subjects with a broad range of pulmonary disorders.