Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study.

OBJECTIVE: It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome. DESIGN: Retrospective analysis of CT images and positron emission tomography images using [F]fluoro-2-deoxy-D-glucose. SETTING: University animal research laboratory. SUBJECTS: Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls. INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal. MEASUREMENTS AND MAIN RESULTS: The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals), which was not observed in the control animals. CONCLUSION: In this porcine acute respiratory distress syndrome model, regional lung strain was spatially correlated with regional inflammation, supporting that strain is a relevant and prominent determinant of ventilator-induced lung injury.

Spatial patterns and frequency distributions of regional deformation in the healthy human lung.

Understanding regional deformation in the lung has long attracted the medical community, as parenchymal deformation plays a key role in respiratory physiology. Recent advances in image registration make it possible to noninvasively study regional deformation, showing that volumetric deformation in healthy lungs follows complex spatial patterns not necessarily shared by all subjects, and that deformation can be highly anisotropic. In this work, we systematically study the regional deformation in the lungs of eleven human subjects by means of in vivo image-based biomechanical analysis. Regional deformation is quantified in terms of 3D maps of the invariants of the right stretch tensor, which are related to regional changes in length, surface and volume. Based on the histograms of individual lungs, we show that log-normal distributions adequately represent the frequency distribution of deformation invariants in the lung, which naturally motivates the normalization of the invariant fields in terms of the log-normal score. Normalized maps of deformation invariants allow for a direct intersubject comparison, as they display spatial patterns of deformation in a range that is common to all subjects. For the population studied, we find that lungs in supine position display a marked gradient along the gravitational direction not only for volumetric but also for length and surface regional deformation, highlighting the role of gravity in the regional deformation of normal lungs under spontaneous breathing.

Improving the Accuracy of Registration-Based Biomechanical Analysis: A Finite Element Approach to Lung Regional Strain Quantification.

Tissue deformation plays an important role in lung physiology, as lung parenchyma largely deforms during spontaneous ventilation. However, excessive regional deformation may lead to lung injury, as observed in patients undergoing mechanical ventilation. Thus, the accurate estimation of regional strain has recently received great attention in the intensive care community. In this work, we assess the accuracy of regional strain maps computed from direct differentiation of B-Spline (BS) interpolations, a popular technique employed in non-rigid registration of lung computed tomography (CT) images. We show that, while BS-based registration methods give excellent results for the deformation transformation, the strain field directly computed from BS derivatives results in predictions that largely oscillate, thus introducing important errors that can even revert the sign of strain. To alleviate such spurious behavior, we present a novel finite-element (FE) method for the regional strain analysis of lung CT images. The method follows from a variational strain recovery formulation, and delivers a continuous approximation to the strain field in arbitrary domains. From analytical benchmarks, we show that the FE method results in errors that are a fraction of those found for the BS method, both in an average and pointwise sense. The application of the proposed FE method to human lung CT images results in 3D strain maps are heterogeneous and smooth, showing high consistency with specific ventilation maps reported in the literature. We envision that the proposed FE method will considerably improve the accuracy of image-based biomechanical analysis, making it reliable enough for routine medical applications.