A respiratory‐gated micro‐CT comparison of respiratory patterns in free‐breathing and mechanically ventilated rats

In this study, we aim to quantify the differences in lung metrics measured in free‐breathing and mechanically ventilated rodents using respiratory‐gated micro‐computed tomography. Healthy male Sprague‐Dawley rats were anesthetized with ketamine/xylazine and scanned with a retrospective respiratory gating protocol on a GE Locus Ultra micro‐CT scanner. Each animal was scanned while free‐breathing, then intubated and mechanically ventilated (MV) and rescanned with a standard ventilation protocol (56 bpm, 8 mL/kg and PEEP of 5 cm H2O) and again with a ventilation protocol that approximates the free‐breathing parameters (88 bpm, 2.14 mL/kg and PEEP of 2.5 cm H2O). Images were reconstructed representing inspiration and end expiration with 0.15 mm voxel spacing. Image‐based measurements of the lung lengths, airway diameters, lung volume, and air content were compared and used to calculate the functional residual capacity (FRC) and tidal volume. Images acquired during MV appeared darker in the airspaces and the airways appeared larger. Image‐based measurements showed an increase in lung volume and air content during standard MV, for both respiratory phases, compared with matched MV and free‐breathing. Comparisons of the functional metrics showed an increase in FRC for mechanically ventilated rats, but only the standard MV exhibited a significantly higher tidal volume than free‐breathing or matched MV. Although standard mechanical ventilation protocols may be useful in promoting consistent respiratory patterns, the amount of air in the lungs is higher than in free‐breathing animals. Matching the respiratory patterns with the free‐breathing case allowed similar lung morphology and physiology measurements while reducing the variability in the measurements.