Dynamic Xenon-Enhanced Spectral CT Imaging to Evaluate Regional Lung Function in an In Vivo Rabbit Model

Background/Objectives: Pulmonary diseases exhibit spatially heterogeneous functional and structural abnormalities that are inadequately represented by conventional lung function testing. This pilot study investigates dynamic xenon-enhanced dual-energy CT (Xe-DECT) for a multiparametric assessment of lung ventilation and tissue. Methods: Four mechanically ventilated rabbits were scanned during washout of 70% xenon in oxygen using multibreath imaging with a clinical DECT both before (baseline) and after methacholine administration (post-MCh). Tracheal Xe concentration (C_Xe) and flow were monitored using mass spectrometry and pneumotachometry to estimate specific ventilation (sV˙ms) and end-expiratory lung volume (EELV_ms). DECT-derived xenon concentration and tissue density images (mg/mL) were obtained by material decomposition, yielding sV˙DECT and EELV_DECT, respectively. Agreement with mass spectrometry and differences between baseline and post-MCh were assessed. Results: The baseline sV˙DECT and EELV_DECT agreed with the mass spectrometry, with mean differences of 0.6 min^-1 [-0.2 min^-1, 1.4 min^-1] and 0.6 mL [-6.7 mL, 7.9 mL], respectively. Following MCh administration, the mean differences increased to -2.9 min^-1 [-4.1 min^-1, -1.6 min^-1] for sV˙ and 1.3 mL [-15.3 mL, 12.8 mL] for EELV. Post-MCh, sV˙DECT decreased from 8.6 ± 1.6 min^-1 to 3.7 ± 0.9 min^-1 (p = 0.034) and EELV_DECT from 29.3 ± 1.0 mL to 27.0 ± 1.3 mL (p = 0.036), whereas sV˙ms (p = 0.308) and EELV_ms (p = 0.653) showed no substantial changes. Regional analysis revealed that sV˙DECT in well-ventilated regions matched tracheal sV˙ms. Conclusions: Dynamic Xe-DECT imaging enabled spatial and quantitative assessments of specific ventilation and tissue densities in an in vivo rabbit model. This technique allowed detection of focal alterations that remained undetected by tracheal measurements.