Non-Invasive Microstructure and Morphology Investigation of the Mouse Lung: Qualitative Description and Quantitative Measurement

Zhang, Lu; Li, Dongyue; Luo, Shuqian

The lungs are composed of sponge-like soft tissues. Detection of soft tissues using conventional absorption-based radiography is limited by the variation in tissue density. Since PCI is a phasesensitive technique, it facilitates the visualization of fine structures, particularly in soft tissues. This technique has opened a new window for the visualization of lung. As a current imaging modality, clinical thin-section CT can be used to visualize airways with an internal diameter larger than 2 mm. It is better than conventional radiography and can provide more detailed information [6] . However, the terminal airspaces cannot be detected via this technique. Micro-CT for laboratory studies has a much higher resolution on the order of microns. Nevertheless, it is still based on the absorption information of the X-ray. The alveolar wall and the air space can not provide sufficient contrast to be observed [20] . A few studies have applied magnetic resonance imaging (MRI) to the lung imaging. Although MRI can provide excellent soft tissue imaging and functional imaging, the limitations lie in the low spatial resolution and long acquisition times [21] . The measurement of bronchial diameter will be hampered by these limitations, because normal spatial resolution of MRI is in the range of 4-6 mm and only a few can reach up to 1 mm [22] . The lung is an air-filled organ. At the air-tissue boundary, the refractive index changes significantly, so the lung becomes highly visible in PCI images. The lung images in our experiment have shown dramatic improvement in quality, and the alveoli can be clearly discerned. The theoretical spatial resolution of our experimental system is about 1 mm, while the diameter of mature mouse alveoli range from 38 to 80 mm and human alveoli are larger at 200-250 mm [15] . Thus, the resolution of PCI is adequate for micro-structures observation in lung. Though the radiation dose in our experiment was relatively larger than that used in clinical imaging, it can be reduced by the use of high energy X-ray, since contrast is not dependent on absorption of the beam [12, 15] . In addition, compared to other existing PCI methods, IL-XPCI requires relatively simple instrument. Most importantly, conventional laboratory X-ray source can be used as the light source, although longer exposure times are required [13] . The equipments are similar to conventional radiography. In this regard, it has the potential to be used in clinical diagnosis. When it comes to studying the architecture of micro-structures in lung, histological biopsy is the most commonly used method [9] . But it is invasive and can not be repeated [10, 23] . During the process of invasive sampling, anesthesia is often required and tissue deformation frequently happen which is a major disadvantage when studying the morphology of the organs. There has long been a desire to explain breathing mechanism at the alveolar level. Unfortunately, a full understanding of these fine structures' original morphology is not available, because the lung will collapse when opening the thoracic cage at autopsy, due to the loss of negative pleural pressure [18] . Some researchers used confocal microscope to evaluate alveolar dynamics in the mouse lungs. However, this technique is limited by the depth of imaging (about 50 mm) [24] . How lungs develop has long fascinated biologists and mathematicians. Nevertheless, this process cannot be visualized in living embryos with current techniques [19