Four-dimensional visualization of subpleural alveolar dynamics in vivo during uninterrupted mechanical ventilation of living swine.

Pulmonary alveoli have been studied for many years, yet no unifying hypothesis exists for their dynamic mechanics during respiration due to their miniature size (100-300 μm dimater in humans) and constant motion, which prevent standard imaging techniques from visualizing four-dimensional dynamics of individual alveoli in vivo. Here we report a new platform to image the first layer of air-filled subpleural alveoli through the use of a lightweight optical frequency domain imaging (OFDI) probe that can be placed upon the pleura to move with the lung over the complete range of respiratory motion. This device enables in-vivo acquisition of four-dimensional microscopic images of alveolar airspaces (alveoli and ducts), within the same field of view, during continuous ventilation without restricting the motion or modifying the structure of the alveoli. Results from an exploratory study including three live swine suggest that subpleural alveolar air spaces are best fit with a uniform expansion (r (2) = 0.98) over a recruitment model (r (2) = 0.72). Simultaneously, however, the percentage change in volume shows heterogeneous alveolar expansion within just a 1 mm x 1 mm field of view. These results signify the importance of four-dimensional imaging tools, such as the device presented here. Quantification of the dynamic response of the lung during ventilation may help create more accurate modeling techniques and move toward a more complete understanding of alveolar mechanics.