Dynamic single-slice CT estimates whole-lung dual-energy CT variables in pigs with and without experimental lung injury

Background Dynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified. Methods Eight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmH2O. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images. Results Mean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r2 0.75–0.94) with agreement between CT density distributions (r 0.89–0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology. Conclusions Overall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.

Semiautomatic segmentation of longitudinal computed tomography images in a rat model of lung injury by surfactant depletion

Quantitative analysis of computed tomography (CT) is essential to the study of acute lung injury. However, quantitative CT is made difficult by poor lung aeration, which complicates the critical step of image segmentation. To overcome this obstacle, this study sought to develop and validate a semiautomated, multilandmark, registration-based scheme for lung segmentation that is effective in conditions of poor aeration. Expiratory and inspiratory CT images were obtained in rats ( n = 8) with surfactant depletion of incremental severity to mimic worsening aeration. Trained operators manually delineated the images to provide a comparative landmark. Semiautomatic segmentation originated from a single, previously segmented reference image obtained at healthy baseline. Deformable registration of the target images (after surfactant depletion) was performed using the symmetric diffeomorphic transformation model with B-spline regularization. Registration used multiple landmarks (i.e., rib cage, spine, and lung parenchyma) to minimize the effect of poor aeration. Then target images were automatically segmented by applying the calculated transformation function to the reference image contour. Semiautomatically and manually segmented contours proved to be highly similar in all aeration conditions, including those characterized by more severe surfactant depletion and expiration. The Dice similarity coefficient was over 0.9 in most conditions, confirming high agreement, irrespective of poor aeration. Furthermore, CT density-based measurements of gas volume, tissue mass, and lung aeration distribution were minimally affected by the method of segmentation. Moving forward, multilandmark registration has the potential to streamline quantitative CT analysis by enabling semiautomatic image segmentation of lungs with a broad range of injury severity.

Effect of Positive End-expiratory Pressure on Regional Ventilation Distribution during Mechanical Ventilation after Surfactant Depletion

Background: Ventilator-induced lung injury occurs due to exaggerated local stresses, repeated collapse, and opening of terminal air spaces in poorly aerated dependent lung, and increased stretch in nondependent lung. The aim of this study was to quantify the functional behavior of peripheral lung units in whole-lung lavage-induced surfactant depletion, and to assess the effect of positive end-expiratory pressure. Methods: The authors used synchrotron imaging to measure lung aeration and regional specific ventilation at positive end-expiratory pressure of 3 and 9 cm H2O, before and after whole-lung lavage in rabbits. Respiratory mechanical parameters were measured, and helium-washout was used to assess end-expiratory lung volume. Results: Atelectatic, poorly, normally aerated, hyperinflated, and trapped regions could be identified using the imaging technique used in this study. Surfactant depletion significantly increased atelectasis (6.3 ± 3.3 [mean ± SEM]% total lung area; P = 0.04 vs. control) and poor aeration in dependent lung. Regional ventilation was distributed to poorly aerated regions with high (16.4 ± 4.4%; P < 0.001), normal (20.7 ± 5.9%; P < 0.001 vs. control), and low (5.7 ± 1.2%; P < 0.05 vs. control) specific ventilation. Significant redistribution of ventilation to normally aerated nondependent lung regions occurred (41.0 ± 9.6%; P = 0.03 vs. control). Increasing positive end-expiratory pressure level to 9 cm H2O significantly reduced poor aeration and recruited atelectasis, but ventilation redistribution persisted (39.2 ± 9.5%; P < 0.001 vs. control). Conclusions: Ventilation of poorly aerated dependent lung regions, which can promote the local concentration of mechanical stresses, was the predominant functional behavior in surfactant-depleted lung. Potential tidal recruitment of atelectatic lung regions involved a smaller fraction of the imaged lung. Significant ventilation redistribution to aerated lung regions places these at risk of increased stretch injury.

Comparison of Static End-expiratory and Effective Lung Volumes for Gas Exchange in Healthy and Surfactant-depleted Lungs

Background: Effective lung volume (ELV) for gas exchange is a new measure that could be used as a real-time guide during controlled mechanical ventilation. The authors established the relationships of ELV to static end-expiratory lung volume (EELV) with varying levels of positive end-expiratory pressure (PEEP) in healthy and surfactant-depleted rabbit lungs. Methods: Nine rabbits were anesthetized and ventilated with a modified volume-controlled mode where periods of five consecutive alterations in inspiratory/expiratory ratio (1:2–1.5:1) were imposed to measure ELV from the corresponding carbon dioxide elimination traces. EELV and the lung clearance index were concomitantly determined by helium wash-out technique. Airway and tissue mechanics were assessed by using low-frequency forced oscillations. Measurements were collected at PEEP 0, 3, 6, and 9 cm H2O levels under control condition and after surfactant depletion by whole-lung lavage. Results: ELV was greater than EELV at all PEEP levels before lavage, whereas there was no evidence for a difference in the lung volume indices after surfactant depletion at PEEP 6 or 9 cm H2O. Increasing PEEP level caused significant parallel increases in both ELV and EELV levels, decreases in ventilation heterogeneity, and improvement in airway and tissue mechanics under control condition and after surfactant depletion. ELV and EELV exhibited strong and statistically significant correlations before (r = 0.84) and after lavage (r = 0.87). Conclusions: The parallel changes in ELV and EELV with PEEP in healthy and surfactant-depleted lungs support the clinical value of ELV measurement as a bedside tool to estimate dynamic changes in EELV in children and infants.

Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation

Inflammation during mechanical ventilation is thought to depend on regional mechanical stress. This can be produced by concentration of stresses and cyclic recruitment in low-aeration dependent lung. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) allows for noninvasive assessment of regional metabolic activity, an index of neutrophilic inflammation. We tested the hypothesis that, during mechanical ventilation, surfactant-depleted low-aeration lung regions present increased regional 18F-FDG uptake suggestive of in vivo increased regional metabolic activity and inflammation. Sheep underwent unilateral saline lung lavage and were ventilated supine for 4 h (positive end-expiratory pressure = 10 cmH2O, tidal volume adjusted to plateau pressure = 30 cmH2O). We used PET scans of injected 13N-nitrogen to compute regional perfusion and ventilation and injected 18F-FDG to calculate 18F-FDG uptake rate. Regional aeration was quantified with transmission scans. Whole lung 18F-FDG uptake was approximately two times higher in lavaged than in nonlavaged lungs (2.9 ± 0.6 vs. 1.5 ± 0.3 10−3/min; P < 0.05). The increased 18F-FDG uptake was topographically heterogeneous and highest in dependent low-aeration regions (gas fraction 10–50%, P < 0.001), even after correction for lung density and wet-to-dry lung ratios. 18F-FDG uptake in low-aeration regions of lavaged lungs was higher than that in low-aeration regions of nonlavaged lungs ( P < 0.05). This occurred despite lower perfusion and ventilation to dependent regions in lavaged than nonlavaged lungs ( P < 0.001). In contrast, 18F-FDG uptake in normally aerated regions was low and similar between lungs. Surfactant depletion produces increased and heterogeneously distributed pulmonary 18F-FDG uptake after 4 h of supine mechanical ventilation. Metabolic activity is highest in poorly aerated dependent regions, suggesting local increased inflammation.