Innovative Methodology In vivo characterization of lung morphology and function in anesthetized free-breathing mice using micro-computed tomography

Ford NL, Martin EL, Lewis JF, Veldhuizen RA, Drangova M, Holdsworth DW. In vivo characterization of lung morphology and function in anesthetized free-breathing mice using micro-computed tomography. J Appl Physiol 102: 2046–2055, 2007. First published Janaury 25, 2007; doi:10.1152/japplphysiol.00629.2006.—Lung morphology and function in human subjects can be monitored with computed tomography (CT). Because many human respiratory diseases are routinely modeled in rodents, a means of monitoring the changes in the structure and function of the rodent lung is desired. High-resolution images of the rodent lung can be attained with specialized micro-CT equipment, which provides a means of monitoring rodent models of lung disease noninvasively with a clinically relevant method. Previous studies have shown respiratory-gated images of intubated and respirated mice. Although the image quality and resolution are sufficient in these studies to make quantitative measurements, these measurements of lung structure will depend on the settings of the ventilator and not on the respiratory mechanics of the individual animals. In addition, intubation and ventilation can have unnatural effects on the respiratory dynamics of the animal, because the airway pressure, tidal volume, and respiratory rate are selected by the operator. In these experiments, important information about the symptoms of the respiratory disease being studied may be missed because the respiration is forced to conform to the ventilator settings. In this study, we implement a method of respiratory-gated micro-CT for use with anesthetized free-breathing rodents. From the micro-CT images, quantitative analysis of the structure of the lungs of healthy unconscious mice was performed to obtain airway diameters, lung and airway volumes, and CT densities at end expiration and during inspiration. Because the animals were free breathing, we were able to calculate tidal volume (0.09 0.03 ml) and functional residual capacity (0.16 0.03 ml).