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We visualized pulmonary acini in the core regions of the mouse lung in situ using synchrotron refraction-enhanced computed tomography (CT) and evaluated their kinematics during quasi-static inflation. This CT system (with a cube voxel of 2.8 μm) allows excellent visualization of not just the conducting airways, but also the alveolar ducts and sacs, and tracking of the acinar shape and its deformation during inflation. The kinematics of individual alveoli and alveolar clusters with a group of terminal alveoli is influenced not only by the connecting alveolar duct and alveoli, but also by the neighboring structures. Acinar volume was not a linear function of lung volume. The alveolar duct diameter changed dramatically during inflation at low pressures and remained relatively constant above an airway pressure of ∼8 cmH2O during inflation. The ratio of acinar surface area to acinar volume indicates that acinar distension during low-pressure inflation differed from that during inflation over a higher pressure range; in particular, acinar deformation was accordion-like during low-pressure inflation. These results indicated that the alveoli and duct expand differently as total acinar volume increases and that the alveolar duct may expand predominantly during low-pressure inflation. Our findings suggest that acinar deformation in the core regions of the lung is complex and heterogeneous.

The interest in small animal models of human diseases has generated a need to design a computed tomography (CT) system that operates at a microscopic level. It is particularly important to be able to visualize the dramatic rhythmical motion of organs such as the heart and lungs. In order to evaluate the motion of the heart and lungs of small animals (rats and mice), we developed in the present study a high-resolution 4D in vivo-CT system for small animals that uses synchrotron radiation. To reduce motion artifacts and the radiation dose, the projections were synchronized with airway pressure, the ECG, the x-ray shutter and the CCD shutter. For cardiovascular imaging, a blood pool contrast agent was injected and the data sets were acquired at several ECG points during the end-expiratory phase. For imaging of the lungs, the data sets were acquired at several airway pressures during diastole. The dynamic motion of the cardiovascular system (the ventricles and coronary arteries) and small airways (diameter > 250 microm of rats and 125 microm of mice) was visualized. This high-resolution imaging tool may be very useful for the development of novel drugs in murine models, in addition to its use in the study of cardiovascular and respiratory physiology.