The spatial and temporal heterogeneity of regional ventilation: Comparison of measurements by two high-resolution methods

High-resolution estimates of ventilation distribution in normal animals utilizing deposition of fluorescent microsphere aerosol (FMS technique) demonstrate substantial ventilation heterogeneity, but this finding has not been confirmed by an independent method. Five supine anesthetized sheep were used to compare the spatial and temporal heterogeneity of regional ventilation measured by both the FMS technique and by a ventilation model utilizing the data from computed tomography images of xenon gas washin (CT/Xe technique). An aerosol containing 1 μm fluorescent microspheres (FMS) was administered via a mechanical ventilator delivering a 2-s end-inspiration hold during each breath. Following the aerosol administration, sequential CT images of a transverse lung slice were acquired during each end-inspiration hold during washin of a 65% Xenon/35% oxygen gas mixture (CT/Xe technique). Four paired FMS and CT/Xe measurements were done at 30 min intervals, after which the animals were sacrificed. The lungs were extracted, air-dried and sliced in 1 cm transverse sections. The lung section corresponding to the CT image was cut into 1 cm3 cubes, with notation of spatial coordinates. The individual cubes were soaked in solvent and the four fluorescent signals were measured with a fluorescence spectrophotometer. The color signals were normalized by the mean signal for all pieces and taken as the FMS estimate of ventilation heterogeneity. The CT images were clustered into 1 cm3 voxels and the rate of increase in voxel density was used to calculate voxel ventilation utilizing the model of Kreck et al. (2001). The regional ventilation voxel measurements were normalized by the mean value to give a CT/Xe estimate of ventilation heterogeneity comparable to the normalized FMS measurements. The overall of heterogeneity of ventilation at the 1 cm3 level of resolution was comparable by both techniques, with substantial differences among animals (coefficient of variation ranging from 37% to 74%). The repeated within-animal measurements by both techniques gave consistent values. Both techniques showed comparable large-scale distribution of regional ventilation in the caudal lobes of the supine animals. There were appreciable differences in the temporal variability of ventilation among animals. This study provides an independent confirmation of the scale-dependent heterogeneity of ventilation described by previous FMS aerosol studies of ventilation heterogeneity.