Background Protective mechanical ventilation (MV) aims at limiting global lung deformation and has been associated with better clinical outcomes in acute respiratory distress syndrome (ARDS) patients. In ARDS lungs without MV support, the mechanisms and evolution of lung tissue deformation remain understudied. In this work, we quantify the progression and heterogeneity of regional strain in injured lungs under spontaneous breathing and under MV. Methods Lung injury was induced by lung lavage in murine subjects, followed by 3 h of spontaneous breathing (SB-group) or 3 h of low V t mechanical ventilation (MV-group). Micro-CT images were acquired in all subjects at the beginning and at the end of the ventilation stage following induction of lung injury. Regional strain, strain progression and strain heterogeneity were computed from image-based biomechanical analysis. Three-dimensional regional strain maps were constructed, from which a region-of-interest (ROI) analysis was performed for the regional strain, the strain progression, and the strain heterogeneity. Results After 3 h of ventilation, regional strain levels were significantly higher in 43.7% of the ROIs in the SB-group. Significant increase in regional strain was found in 1.2% of the ROIs in the MV-group. Progression of regional strain was found in 100% of the ROIs in the SB-group, whereas the MV-group displayed strain progression in 1.2% of the ROIs. Progression in regional strain heterogeneity was found in 23.4% of the ROIs in the SB-group, while the MV-group resulted in 4.7% of the ROIs showing significant changes. Deformation progression is concurrent with an increase of non-aerated compartment in SB-group (from 13.3% ± 1.6% to 37.5% ± 3.1%), being higher in ventral regions of the lung. Conclusions Spontaneous breathing in lung injury promotes regional strain and strain heterogeneity progression. In contrast, low V t MV prevents regional strain and heterogeneity progression in injured lungs.

IntroductionBreathing produces a phenomenon of cyclic deformation throughout life. Biomechanically, deformation of the lung is measured as strain. Regional strain recently started to be recognised as a tool in the study of lung pathophysiology, but regional lung strain has not been studied in healthy subjects breathing spontaneously without voluntary or pharmacological control of ventilation. Our aim is to generate three-dimensional (3D) regional strain and heterogeneity maps of healthy rat lungs and describe their changes over time.MethodsMicro-CT and image-based biomechanical analysis by finite element approach were carried out in six anaesthetised rats under spontaneous breathing in two different states, at the beginning of the experiment and after 3 hours of observation. 3D regional strain maps were constructed and divided into 10 isovolumetric region-of-interest (ROI) in three directions (apex to base, dorsal to ventral and costal to mediastinal), allowing to regionally analyse the volumetric strain, the strain progression and the strain heterogeneity. To describe in depth these parameters, and systematise their report, we defined regional strain heterogeneity index [1+strain SD ROI(x)]/[1+strain mean ROI(x)] and regional strain progression index [ROI(x)−mean of final strain/ROI(x)−mean of initial strain].ResultsWe were able to generate 3D regional strain maps of the lung in subjects without respiratory support, showing significant differences among the three analysed axes. We observed a significantly lower regional volumetric strain in the apex sector compared with the base, with no significant anatomical systematic differences in the other directions. This heterogeneity could not be identified with physiological or standard CT methods. There was no progression of the analysed regional volumetric strain when the two time-points were compared.DiscussionIt is possible to map the regional volumetric strain in the lung for healthy subjects during spontaneous breathing. Regional strain heterogeneity and changes over time can be measured using a CT image-based numerical analysis applying a finite element approach. These results support that healthy lung might have significant regional strain and its spatial distribution is highly heterogeneous. This protocol for CT image acquisition and analysis could be a useful tool for helping to understand the mechanobiology of the lung in many diseases.

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