Abstract
Most measures of lung health independently characterise either global lung function or regional lung structure. The ability to measure airflow and lung function regionally would provide a more specific and physiologically focused means by which to assess and track lung disease in both pre-clinical and clinical settings. One approach for achieving regional lung function measurement is via phase contrast X-ray imaging (PCXI), which has been shown to provide highly sensitive, high-resolution images of the lungs and airways in small animals. The detailed images provided by PCXI allow the application of four-dimensional X-ray velocimetry (4DxV) to track lung tissue motion and provide quantitative information on regional lung function. However, until recently synchrotron facilities were required to produce the highly coherent, high-flux X-rays that are required to achieve lung PCXI at a high enough frame rate to capture lung motion. This paper presents the first translation of 4DxV technology from a synchrotron facility into a laboratory setting by using a liquid-metal jet microfocus X-ray source. This source can provide the coherence required for PCXI and enough X-ray flux to image the dynamics of lung tissue motion during the respiratory cycle, which enables production of images compatible with 4DxV analysis. We demonstrate the measurements that can be captured in vivo in live mice using this technique, including regional airflow and tissue expansion. These measurements can inform physiological and biomedical research studies in small animals and assist in the development of new respiratory treatments.
Highlights
Most measures of lung health independently characterise either global lung function or regional lung structure
An ideal assessment technique would be able to obtain dynamic functional measures such as airflow in a regional manner to identify the location of any functional changes, and understand how they contribute to global changes in parameters such as FEV1
We present dynamic 4DxV in vivo images of the lungs and airways of live mice acquired on a laboratory X-ray source at 30 frames per second
Summary
Most measures of lung health independently characterise either global lung function or regional lung structure. This paper presents the first translation of 4DxV technology from a synchrotron facility into a laboratory setting by using a liquid-metal jet microfocus X-ray source This source can provide the coherence required for PCXI and enough X-ray flux to image the dynamics of lung tissue motion during the respiratory cycle, which enables production of images compatible with 4DxV analysis. Studies have attempted to measure dynamic lung motion in humans by comparing CT scans at different respiratory phases (e.g. end-inspiratory and end-expiratory), to measure tissue deformation for tumour identification and tracking[5,6,7] This type of technology has not become common clinical practice, and has not been widely utilised outside of tumour motion evaluation. The availability of these methods in pre-clinical research would allow tracking of regional respiratory disease progression or response to therapies over time in the same animal, reduce animal numbers, improve statistical power, and provide additional information to researchers that is not currently available
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