MAGNIFY SRC: Pulmonary Magnetic Resonance Imaging for Cystic Fibrosis
A Trust-funded Strategic Research Centre will investigate whether Magnetic Resonance Imaging (MRI) could be used to track changes in lung health over time. New MRI methods have been developed by the POLARIS group at University of Sheffield led by Professor Jim Wild, the Principal Investigator of this SRC.
Prof Jim Wild and Dr Laurie Smith will lead a collaborative, multidisciplinary programme of research – involving researchers at Sheffield, Manchester and Nottingham Universities – to investigate how and whether these MRI methods can be incorporated into CF clinical practice, including developing easy-to-use software to process the MRI data, and working out the best ways to support CF clinicians and the people with CF and families they care for, in understanding the significance of this new information for people’s lung health.
The MRI images were developed in Sheffield over the last 20 years with CF always in mind. As such this SRC will build on long standing relationships with the CF teams at Sheffield Children's Hospital and Sheffield Teaching Hospitals, where people with CF will be key to the success of the research programme.
If successfully adopted into CF care, these new MRI methods could give a safe, easy to perform and more detailed assessment of the lung health of people with CF and reduce their exposure to x-rays (for example, fewer CT scans and chest x-rays).
The programme is co-funded by the Trust and the CF Foundation in the United States.
Why is this research needed?
With the changing nature of cystic fibrosis, it is important that we continue to develop new ways to monitor people’s health. This information could be used to manage their condition from day to day, and also to find out the effectiveness of new treatments being tested in CF clinical trials.
People with CF on CFTR modulators medicines such as Kaftrio, it can be much harder to spot any flare ups of lung infection, or changes in lung function. This might be as they have fewer lung symptoms than before they had access to these medicines.
New types of CF treatment, such as CF genetic therapies that have the potential to benefit everyone with CF, are starting to be tested in clinical trials. Doctors and researchers need to be able to see any changes in lung function due to these medicines as soon as possible.
The researchers want to study whether new methods of studying lung function they have developed using Magnetic Resonance Imaging (MRI) could be used to assess lung function in people with CF.
Understanding the Strategic Research Centre research in more detail
Getting the best MRI scan results
Prof Wild will lead a series of studies to ensure that the team know how to get the best results from the MRI scans of the lungs of people with CF. They will test the programming for the scans, make adjustments for different types of scanner and develop software to present the scan results in a clear way for the CF Team.
There are many different types of MRI scan, that can give a range of different information about the part of the body being scanned. Different information can be obtained by changing the settings on the scanner or changing the programming of the scanner. Some types of scan require people to receive a ‘contrast agent’ to make the images more detailed and in the case of some of the lung MRI scans being tested in this research, this requires people to breathe in a harmless gas called Xenon during the scan.
In addition, MRI scanners in different hospitals are built slightly differently. Adjustments need to be made to ensure its possible to compare the results from different MRI scanners. Finally, the readout from the scanner needs to be converted into meaningful information for the clinical teams and their patients.
Using lung MRI scans in clinical trials
MRI scans can detect changes in how the lungs work in people with CF, before any changes are detected using standard measures of lung function, such as FEV1. In a workpackage led by Dr Smith, the researchers want to test whether MRI methods could be used in clinical trials of new medicines, as evidence of a beneficial effect.
It is important that researchers studying the results of clinical trials are confident of whether any differences in lung function they detect are changes are due to the new medicine, in comparison to day-to-day variations in lung function. An example of a day to day change could be a dip in lung function due to a flare up of CF lung infection.
As an example of whether this is possible, they will compare the MRI scans before and after treatment with CFTR modulators. They will do this by asking people who took part in a previous research study to take part in a new study. The first research study was done before access to CFTR modulators was agreed in the UK. They will ask people who are on CFTR modulators in this group to take part in new research and have further MRI scans.
The researchers will also conduct studies in people with CF who are not taking CFTR modulators. If MRI methods are used in future clinical trials of new medicines such as genetic therapies, having results before the new medicines are tested will provide a rapid way of testing their effectiveness.
Understanding what MRI scan results mean
MRI scans results will provide detailed information about the lungs of people with CF and the images are very easy to understand. They may show new, worse-than-expected assessment of their lung health that may be a concern and surprise to the person with CF. Alongside practical and clinical aspects of developing the new lung MRI tests (described above), Nottingham-based researchers Dan Beever, Dr Laura Howell and Dr Andrew Prayle and colleagues will explore the best way to share the results with clinicians and with people with CF, and develop some guidance on sharing this new health information.
Learning more about how lung damage affects breathing and drug delivery
The lungs are made up of smaller and smaller-sized passageways that branch out (literally like branches of a tree), making some parts of the lungs quite separate to other parts. If people are taking inhaled medicines, it is important to understand which parts of the lung the medicines are reaching. For people with CF, there may be temporary blockages or permanent lung damage that can affect which parts of the lung are used. Dr Whitfield and Prof Horsley at the University of Manchester will lead a workpackage using MRI lung scans and computer models to help understand more about how the lungs of people with CF inflate as they breathe. This will provide vital new information to help the design of many new CF medicines, including new CF genetic therapies.
Principal investigator: Professor Jim Wild, POLARIS group, University of Sheffield
Co-investigators:
Dr Laurie Smith, POLARIS group, University of Sheffield
Professor Alex Horsley, University of Manchester & Manchester Adult CF Centre
Dr Andrew Prayle, University of Nottingham
Dr Laura Howells, University of Nottingham
Dan Beever, University of Nottingham
Dr Carl Whitfield, Department of Mathematics, University of Manchester