Aeration of the lung and the transition to air-breathing at birth is fundamental to mammalian life and initiates major changes in cardiopulmonary physiology. However, the dynamics of this process and the factors involved are largely unknown, because it has not been possible to observe or measure lung aeration on a breath-by-breath basis. We have used the high contrast and spatial resolution of phase contrast X-ray imaging to study lung aeration at birth in spontaneously breathing neonatal rabbits. As the liquid-filled fetal lungs provide little absorption or phase contrast, they are not visible and only become visible as they aerate, allowing a detailed examination of this process. Pups were imaged live from birth to determine the timing and spatial pattern of lung aeration, and relative levels of lung aeration were measured from the images using a power spectral analysis. We report the first detailed observations and measurements of lung aeration, demonstrating its dependence on inspiratory activity and body position; dependent regions aerated at much slower rates. The air/liquid interface moved toward the distal airways only during inspiration, with little proximal movement during expiration, indicating that trans-pulmonary pressures play an important role in airway liquid clearance at birth. Using these imaging techniques, the dynamics of lung aeration and the critical role it plays in regulating the physiological changes at birth can be fully explored.

High quality real-time imaging of lungs in vivo presents considerable challenges. We demonstrate here that phase contrast x-ray imaging is capable of dynamically imaging the lungs. It retains many of the advantages of simple x-ray imaging, whilst also being able to map weakly absorbing soft tissues based on refractive index differences. Preliminary results reported herein show that this novel imaging technique can identify and locate airway liquid and allows lung aeration in newborn rabbit pups to be dynamically visualized.

We develop a deterministic algorithm for coherent diffractive imaging (CDI) that employs a modified Fourier transform of a Fraunhofer diffraction pattern to quantitatively reconstruct the complex scalar wavefield at the exit surface of a sample of interest. The sample is placed in a uniformly-illuminated rectangular hole with dimensions at least two times larger than the sample. For this particular scenario, and in the far-field diffraction case, our non-iterative reconstruction algorithm is rapid, exact and gives a unique analytical solution to the inverse problem. The efficacy and stability of the algorithm, which may achieve resolutions in the nanoscale range, is demonstrated using simulated X-ray data.

The significant degree of X-ray phase contrast created by air-tissue interfaces, coupled with the poor radiographic contrast of conventional chest radiographs, makes the inflated lung an ideal candidate for investigating the potential diagnostic improvement afforded by phase contrast X-ray imaging. In small animals these methods highlight the lung airways and lobe boundaries and reveal the lung tissue as a speckled intensity pattern not seen in other soft tissues. We have compared analyser-based and propagation-based phase contrast imaging modalities, together with conventional radiographic imaging, to ascertain which technique shows the greatest image enhancement for various lung sizes. The conventional radiographic image of a mouse was obtained on a Siemens Nova 3000 mammography system, whilst phase contrast images of mice and rabbit chests were acquired at the medical imaging beamline (20B2) at the SPring-8 synchrotron radiation research facility in Japan. For mice aged 1 day, 1 week and 1 month old it was determined that analyser-based imaging showed the greatest overall image contrast, however, for an adult rabbit both techniques yielded excellent contrast. The success of these methods in creating high quality images for rabbit lungs raises the possibility of improving human lung imaging using phase contrast techniques.