AbstractResearch objective: Our in vivo small animal studies utilise synchrotron and laboratory X-ray sources to capture four-dimensional computed tomography (4DCT) of mouse and rat lungs. We apply 4D X-ray velocimetry (4DXV) to the images to measure the regional lung expansion, extracting high-resolution lung function measures throughout the breath cycle. In addition, these images provide quantitative information on the lung structure, including the small airways and the blood vessels. Methods: The 4DCT imaging is gated to the breath cycle of the mechanically-ventilated small animal. Each image in the 4DCT series is post-processed using a mirror symmetry algorithm and automated lung masking method for automatic alignment and cropping, before the 4DXV is applied. To enhance the “vessel-like” structures in the lung, a hessian filtering method is used. This also provides measurements of the airways or blood vessel diameters, without the administration of a contrast agent. Results: We have used these techniques quantify the dead space ventilation in mechanically-ventilated mice, and in an asthma model, elucidated a ‘paradoxical’ dilation in response to methacholine bronchoconstrictor. In cystic fibrosis studies, the 4DXV technique enabled regional lung expansion to be grouped as clustered or heterogeneous. In a study of the pulmonary blood vessels in hypoxic mice, measurements of the diameters were used to quantify vasoconstriction. Conclusions: Our dynamic in vivo X-ray imaging method captures the structure and function of the lung, giving insights into important measures of lung health. New methods of automatic processing will accelerate applications in a range of medical research.
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