Ventilatory heterogeneity in the normal human lung is unchanged by controlled breathing

Abstract

Measurement of ventilation heterogeneity with the multiple-breath nitrogen washout (MBW) is usually performed using controlled breathing with a fixed tidal volume and breathing frequency. However, it is unclear whether controlled breathing alters the underlying ventilatory heterogeneity. We hypothesized that the width of the specific ventilation distribution (a measure of heterogeneity) would be greater in tests performed during free breathing compared with those performed using controlled breathing. Eight normal subjects (age range = 23-50 yr, 5 female/3 male) twice underwent MRI-based specific ventilation imaging consisting of five repeated cycles with the inspired gas switching between 21% and 100% O₂ every ~2 min (total imaging time = ~20 min). In each session, tests were performed with free breathing (FB, no constraints) and controlled breathing (CB) at a respiratory rate of 12 breaths/min and no tidal volume control. The specific ventilation (SV) distribution in a mid-sagittal slice of the right lung was calculated, and the heterogeneity was calculated as the full width at half max of a Gaussian distribution fitted on a log scale (SV width). Free breathing resulted in a range of breathing frequencies from 8.7 to 15.9 breaths/min (mean = 11.5 ± 2.2, P = 0.62, compared with CB). Heterogeneity (SV width) was unchanged by controlled breathing (FB: 0.38 ± 0.12; CB: 0.34 ± 0.09, P = 0.18, repeated-measures ANOVA). The imposition of a controlled breathing frequency did not significantly affect the heterogeneity of ventilation in the normal lung, suggesting that MBW and specific ventilation imaging as typically performed provide an unperturbed measure of ventilatory heterogeneity.NEW & NOTEWORTHY By using MRI-based specific ventilation imaging (SVI), we showed that the heterogeneity of specific ventilation was not different comparing free breathing and breathing with the imposition of a fixed breathing frequency of 12 breaths/min. Thus, multiple-breath washout and SVI as typically performed provide an unperturbed measure of ventilatory heterogeneity.

Keywords: MBW; SVI; washout.

Fig. 1.

Example of the results from one subject (FB08, first session) showing the spatial maps of a typical specific ventilation (SV) distribution for the controlled breathing session (A) and the corresponding distribution of SV (B, blue line) and the associated Gaussian fit (B, red line). C and D show the same information in the same subject for the free-breathing acquisition. The frequency histogram of the number of voxels with a specific SV is plotted on a log scale covering the SV range of 0.01 to 10. SV bins are equally spaced on this log scale with each successive bin having an SV 15% higher than the preceding. The corresponding log-Gaussian fit is shown in red.

Fig. 2.

Regression comparing large boxes (12 × 12 grid) for the specific ventilation (SV) within the lung region of interest (ROI) for all subjects and both runs. SV (labeled in log scale) in each large voxel measured during the controlled breathing run (x-axis) is compared with the SV in the same large voxel measured during the free-breathing run (y-axis). The line of identity is shown as the grey dashed line and the line of best fit (perpendicular regression) as the solid line. The prediction interval for the fitted line is shown as the dotted lines. The prediction interval is the region in which, based on the observations, 95% of future observations would fall. Note that the line of identity falls within the prediction interval. n = 1,487 pairs, slope = 1.10 ± 0.03, intercept 0.05 ± 0.04. Line slope significantly different to zero, P < 0.001.

Fig. 3.

Bland–Altman plot of the spatial measures for specific ventilation (SV) from the controlled breathing and the free-breathing runs for both runs from all 8 subjects (1,487 pairs of large voxels, see text for details). Bias 0.012 (red line), SD = 0.083. Dashed lines show the Bias ± 1 SD.

Fig. 4.

Individual and group values of mean specific ventilation (SV) (A) and the width of the SV distribution (B) for the three conditions considered [controlled: controlled breathing, F-B Actual: free breathing analyzed using the measured breathing frequency, F-B Assumed: free breathing analyzed using an assumed breathing frequency of 12 breaths/min]. The average individual breathing frequency of each subject in breaths per minute during the free-breathing test is shown numerically beside the F-B Actual data in A. Subject numbers are shown to the left of each panel to permit identification of individual subject responses.