Effects of Lung Injury on Regional Aeration and Expiratory Time Constants: Insights From Four-Dimensional Computed Tomography Image Registration

Rationale: Intratidal changes in regional lung aeration, as assessed with dynamic four-dimensional computed tomography (CT; 4DCT), may indicate the processes of recruitment and derecruitment, thus portending atelectrauma during mechanical ventilation. In this study, we characterized the time constants associated with deaeration during the expiratory phase of pressure-controlled ventilation in pigs before and after acute lung injury using respiratory-gated 4DCT and image registration. Methods: Eleven pigs were mechanically ventilated in pressure-controlled mode under baseline conditions and following an oleic acid model of acute lung injury. Dynamic 4DCT scans were acquired without interrupting ventilation. Automated segmentation of lung parenchyma was obtained by a convolutional neural network. Respiratory structures were aligned using 4D image registration. Exponential regression was performed on the time-varying CT density in each aligned voxel during exhalation, resulting in regional estimates of intratidal aeration change and deaeration time constants. Regressions were also performed for regional and total exhaled gas volume changes. Results: Normally and poorly aerated lung regions demonstrated the largest median intratidal aeration changes during exhalation, compared to minimal changes within hyper- and non-aerated regions. Following lung injury, median time constants throughout normally aerated regions within each subject were greater than respective values for poorly aerated regions. However, parametric response mapping revealed an association between larger intratidal aeration changes and slower time constants. Lower aeration and faster time constants were observed for the dependent lung regions in the supine position. Regional gas volume changes exhibited faster time constants compared to regional density time constants, as well as better correspondence to total exhaled volume time constants. Conclusion: Mechanical time constants based on exhaled gas volume underestimate regional aeration time constants. After lung injury, poorly aerated regions experience larger intratidal changes in aeration over shorter time scales compared to normally aerated regions. However, the largest intratidal aeration changes occur over the longest time scales within poorly aerated regions. These dynamic 4DCT imaging data provide supporting evidence for the susceptibility of poorly aerated regions to ventilator-induced lung injury, and for the functional benefits of short exhalation times during mechanical ventilation of injured lungs.