Published in the American Journal of Respiratory and Critical Care Medicine, entitled, “Regional Image Based Pulmonary Function Testing Detects CF Lung Disease Earlier Than Conventional PFT,” the imaging method allows researchers to monitor the effectiveness of a treatment for the life-threatening genetic disorder.
Cystic fibrosis affects many of the body’s systems, but most severely the lungs, and currently it can take several months to measure how effective treatment is for the early-fatal lung disease.
In a release, Dr. Kaye Morgan, lead researcher on the paper, says the new x-ray imaging method allows researchers to look at soft tissue structures, for example the brain, airways and lungs, which are effectively invisible in conventional x-ray images.
Dr. Morgan works in the Monash University Faculty of Science at Melbourne as a Research Fellow on a Discovery Early Career Researcher Award. Her research is focused on developing sensitive, high-resolution phase contrast x-ray imaging for live observation of the airway surface. This imaging is currently being utilized to monitor the effectiveness of new treatments for Cystic Fibrosis.
“At the moment we typically need to wait for a cystic fibrosis treatment to have an effect on lung health, measured by either a lung CT scan or breath measurement, to see how effective that treatment is,” Dr Morgan says. “However the new imaging method allows us for the first time to non-invasively see how the treatment is working ‘live’ on the airway surface.”
Dr Morgan explains that this x-ray imaging method can enable doctors and researchers to measure how effective treatments are, and progress new treatments to the clinic at a much quicker rate, a key goal of co-authors Dr. Martin Donnelley, Visiting Research Fellow, School of Pediatrics and Reproductive Health at University of Adelaide, and Medical Scientist at Women’s and Children’s Hospital, and Dr. David Parsons , an Associate Professor and leader of the CF Gene Therapy group at Adelaide’s Women’s and Children’s Hospital and the University of Adelaide’s Robinson Research Institute Gene Therapy refers to a form of treatment that involves inserting one or more corrective genes that have been designed in the laboratory, into the genetic material of a patient’s cells to cure a genetic disease.
“Because we will be able to see how effectively treatments are working straight away, we’ll be able to develop new treatments a lot more quickly, and help better treat people with cystic fibrosis,” says Dr Morgan in the release, noting that the new imaging method, which was developed using a synchrotron x-ray source, may also open up possibilities in assessing how effective treatments were for other lung, heart and brain diseases.
The Cystic Fibrosis Research Group aims to develop an effective genetic therapy for prevention or treatment of cystic fibrosis airway disease. Research activities are focused on achieving effective lentiviral CFTR vector gene delivery, transduction of airway stem cells in situ to enable extended gene expression, and development of rapid and accurate outcome measures for assessment of airway disease and the effects of novel therapeutics.
Group research conducted during 2012 was centered on developing novel synchrotron based techniques for assessing airways physiological function. A collaborative project with physicists from Monash University and the Australian Synchrotron was established to develop novel X-ray imaging approaches effective in living mouse airways, which was reported in an Open Access PLOS 1 paper published last year entitled: “Measuring Airway Surface Liquid Depth in Ex Vivo Mouse Airways by X-Ray Imaging for the Assessment of Cystic Fibrosis Airway Therapies” (Published: January 30, 2013 DOI: 10.1371/journal.pone.0055822), coauthored by Kaye S. Morgan, David M. Paganin, Karen K. W. Siu, and Andreas Fouras of Monash University, Naoto Yagi, Yoshio Suzuki, Akihisa Takeuchi, and Kentaro Uesugi, of the SPring-8/Japan Synchrotron Radiation Research Institute, Kouto, Hyogo, Japan; Richard C. Boucher of the Cystic Fibrosis Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina, and Martin Donnelley and David W. Parsons of Women’s and Children’s Hospital, Adelaide, and the University of Adelaide.
The coauthors note that “In the airways of those with cystic fibrosis (CF), the leading pathophysiological hypothesis is that an ion channel defect results in a relative decrease in airway surface liquid (ASL) volume, producing thick and sticky mucus that facilitates the establishment and progression of early fatal lung disease. This hypothesis predicts that any successful CF airway treatment for this fundamental channel defect should increase the ASL volume, but up until now there has been no method of measuring this volume that would be compatible with in vivo monitoring. In order to accurately monitor the volume of the ASL, we have developed a new x-ray phase contrast imaging method that utilizes a highly attenuating reference grid. In this study we used this imaging method to examine the effect of a current clinical CF treatment, aerosolized hypertonic saline, on ASL depth in ex vivo normal mouse tracheas, as the first step towards non-invasive in vivo ASL imaging.”
This approach is now under development for translation into a potential human application. Working with a mouse model of cystic fibrosis, experimental studies were also performed at the Spring-8 synchrotron in Japan during 2012. The technology allowed visualization of lung mucociliary transit by tracking the movement of inhaled particles over time. The impact of pharmaceutical treatments on mucociliary transit and airway surface liquid depth (a critical controller of airway health) could then be assessed. A large amount of very promising imaging data was captured; analysis of those results continues now. Using the same model, gene therapy studies uncovered preliminary but exciting indications that delivery of correctly-functioning CFTR genes into the affected airways of mice results in increased survival.
Dr. Parsons notes on his Web page that this appears to be the first time cystic fibrosis gene therapy has shown a survival benefit, and that current Group work is focused on extending and confirming these exciting early results.
University of Adelaide
Women’s and Children’s Hospital (Adelaide)
University of Adelaide