Using X-ray velocimetry to measure lung function and assess the efficacy of a pseudomonas aeruginosa bacteriophage therapy for cystic fibrosis.

Phase contrast x-ray imaging (PCXI) provides high-contrast images of weakly-attenuating structures like the lungs. PCXI, when paired with 4D X-ray Velocimetry (XV), can measure regional lung function and non-invasively assess the efficacy of emerging therapeutics. Bacteriophage therapy is an emerging antimicrobial treatment option for lung diseases such as cystic fibrosis (CF), particularly with increasing rates of multi-drug-resistant infections. Current efficacy assessment in animal models is highly invasive, typically requiring histological assessment. We aim to use XV techniques as non-invasive alternatives to demonstrate efficacy of bacteriophage therapy for treating Pseudomonas aeruginosa CF lung infections, measuring functional changes post-treatment. Time-resolved in vivo PCXI-CT scans of control, Pseudomonas-infected, and phage-treated mouse lungs were taken at the Australian Synchrotron Imaging and Medical Beamline. Using XV we measured local lung expansion and ventilation throughout the breath cycle, analysing the skew of the lung expansion distribution. CT images allowed visualisation of the projected air volume in the lungs, assessing structural lung damage. XV analysis demonstrated changes in lung expansion between infection and control groups, however there were no statistically significant differences between treated and placebo groups. In some cases where structural changes were not evident in the CT scans, XV successfully detected changes in lung function.
Competing Interests: Declaration. Competing interests: Martin Donnelley and Stephen Dubsky own shares in 4DMedical. Stephanie A. Harker, Melissa Preissner, Rachel Yoon Chang, David Trevascus, Chengxi Liu, Yuncheng Wang, Michael Yee Chow, Patricia Cmielewski, Nicole Reyne, Ying Ying How, James A. Pollock, Mitzi Klein, Christopher A. Wright, Hak-Kim Chan, and Kaye S. Morgan have no competing interests.
(© 2024. The Author(s).)