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J Appl Physiol (January 25, 2007). doi:10.1152/japplphysiol.00629.2006
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Submitted on June 5, 2006
Accepted on January 19, 2007

In vivo characterization of lung morphology and function in anaesthetized free-breathing mice using non-invasive micro-computed tomography

Nancy L Ford1*, Erica L Martin2, James F. Lewis3, Ruud A.W. Veldhuizen4, Maria Drangova5, and David Wayne Holdsworth6

1 Imaging, Robarts Research Institute, London , Canada
2 Physiology and Pharmacology, University of Western Ontario, London, Canada; n/a, Lawson Research Institute, Room G454, London, Canada
3 Division of Respirology, St. Joseph's Health Center, London, Canada; Physiology and Pharmacology, University of Western Ontario, London, Canada
4 n/a, Lawson Research Institute, Room G454, London, Canada; Physiology and Pharmacology, University of Western Ontario, London, Canada
5 London , Canada; Imaging, Robarts Research Institute, London , Canada; Diagnostic Radiology and Nuclear Medicine, University of Western Ontario, London , Canada; Medical Biophysics, University of Western Ontario, London , Canada
6 Imaging Robarts Research, Robarts Research Institute, London , Canada; Diagnostic Radiology and Nuclear Medicine, University of Western Ontario, London , Canada; Medical Biophysics, University of Western Ontario, London , Canada

* To whom correspondence should be addressed. E-mail: nford{at}imaging.robarts.ca.

Lung morphology and function in human subjects can be monitored with computed tomography. Since 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-computed tomography equipment, which provides a means of monitoring rodent models of lung disease non-invasively with a clinically relevant method. Previous studies have shown respiratory-gated images of intubated and respirated mice. Although the image quality and resolution is sufficient in these studies to make quantitative measurements, these measurements of lung structure will depend on the settings of the ventilator, 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, as the airway pressure, tidal volume and 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-computed tomography for use with anaesthetized 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. Since 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).




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