By Mathieu Boudreau
This MRM Highlights Pick interview is with Sang Hun Chung, Yueh Lee, and Jennifer Goralski, researchers at the University of North Carolina in Chapel Hill, North Carolina. Their paper is entitled “Comparison of single breath hyperpolarized 129Xe MRI with dynamic 19F MRI in cystic fibrosis lung disease” and it was chosen as this month’s Reproducible Research pick because they shared code and data that reproduce several of their figures.
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MRMH: Could you please tell us a little about yourselves and how you came to be involved in this project?
Sang: I am a graduate student doing a PhD in biomedical engineering, and Dr. Lee is my advisor. When I first entered the field of MRI, I was working only on fluorine, but I then progressed to doing some wash-in and wash-out analysis with xenon. For this paper, my main responsibility was the data processing.
Jennifer: I am a physician-scientist — an MD trained in pulmonary/critical care and pediatric pulmonology. My clinical area of interest is cystic fibrosis. Yueh and I started a research collaboration in 2014 to pursue a shared interest in exploring outcome measures that could be used, in particular, to image ventilation. With the help of our colleague, Dr. Cecil Charles at Duke, I have therefore developed a special interest in working with perfluorinated gas MRI.
Yueh: I’m a neuroradiologist, but my PhD field was MR physics. I have therefore always had more of a translational approach to medical imaging in general. I’ve been responsible for the technical component in getting the fluorine-19 work started up here at UNC, while Jen’s really been the clinical component of this collaboration. Sang, our PhD student, has performed the heavy lifting in keeping the system running and in the data analysis. We’re very excited to be able to take this work straight into humans and really help move CF research simultaneously.
MRMH: Could you give us a brief overview of the paper?
Sang: In this study we compared fluorine MRI (where we scan multiple breaths of perfluorinated gas to image dynamic ventilation) with hyperpolarized xenon imaging in a set of ten patients with mild cystic fibrosis. Regarding the fluorine data we acquired, we analyzed early breath data (first breath) separately from the maximum ventilation data (last breath), whereas for the hyperpolarized xenon imaging we compared low-resolution scans and high-resolution scans. We compared the VDP (ventilation defect percentage) values measured in each condition and also compared the correlations between each pair of datasets.
Jennifer: We knew it was going to be an uphill battle when we first decided to study perfluorinated gas rather than hyperpolarized gas, which (in the cystic fibrosis world, at least) is becoming more mainstream. We really wanted to try to perform as direct a comparison as possible between these two modalities. I was a little bit surprised at some of the ventilation defect mismatches we observed (these occur when the two gases fail to detect the same VDPs). In my view, the occurrence of these mismatches really does highlight what we gain from getting a dynamic image using multiple breaths of perfluorinated gas as opposed to a single breath, and it also shows that these imaging modalities could complement each other well. Also, there has recently been a major transformational shift in the care of cystic fibrosis patients, thanks to the availability of CFTR modulators, which are drugs that target the genetic defect underlying the disease. The traditional outcome measures that we depend on for tracking the disease clinically are not going to be relevant much longer. And so, having another, potentially more sensitive, tool that can allow us to detect changes in the disease state is really important to the cystic fibrosis community right now.
Yueh: The xenon imaging world is very well established and has multiple groups who are very experienced. We were fortunate to have Dr. Rosa Tamara Branca here on our campus as a resource to collaborate with us on that side of this work. It was great to be able to work with her and develop this protocol, focusing very much on making that direct comparison with fluorine. As mentioned, we stumbled on these very interesting mismatches, and trying to work through those was a little worrisome at first. Thankfully, we had a broad group of collaborators and concluded that something real was driving the signal in the mismatched areas.
MRM: What are your main takeaways from this study?
Sang: What we observed was that the VDP calculation seems to be dependent on a lot of things, such as the different imaging resolutions for xenon. So that is something to bear in mind. And with fluorine, the slow filling of the air spaces may lead to a mismatch between single versus repeated breaths of gas, which in turn may result in some areas being miscategorized as ventilation defects, whereas in fact they may just be slow-filling areas.
Yueh: I think the mismatch is the critical area, where obviously there’s something going on with the xenon signal that is unusual and different compared with fluorine. And so, I think there’s a lot of interesting physiology that, ironically, can be derived from the xenon side of things, but that fluorine can’t get at in the same way.
Jennifer: The real challenge we faced with the data analysis and interpretation was related to the difference in lung inflation: in other words, the fact that the gas the subjects breathed was a fixed volume in our xenon inhalation scans, as opposed to tidal breathing and then breathing to inspiratory capacity on our 19F scans.
MRMH: You shared coding data with your paper – is this something you normally do for all your papers?
Yueh: This is the first time that we have shared code and data to this extent. When you’re in these smaller research fields, having other people look at your data and process it in different ways to explore new opportunities is always exciting.
Jennifer: The scientific community as a whole has benefited from more open sharing of science, as evidenced by the Covid vaccination projects. I’ve had a lot of patients ask, how is it possible that these vaccines got approved so fast? And when you really delve into it, you find that it is largely because people were open about sharing their science, which allowed scientific progress to be made more rapidly. So, I think that this is the direction science should be moving in.
MRMH: You are all lung imaging researchers – I imagine the past year hasn’t been easy for you, because of the pandemic. How have you adapted?
Jennifer: Yes, it’s been a challenge for sure. We essentially lost three months where no one was even allowed in the lab or the imaging center until we got better access to Covid testing and PPE. When we reopened in June, there were a lot of rules needing to be respected, such as wearing PPE, screening patients for symptoms, and doing Covid testing prior to certain procedures such as spirometry.
Yueh: It was also challenging because Jen, as a clinician, also works in the ICU, so she’s actually caring for these Covid patients. So, on top of everything else, and trying to keep her research going, she was on the frontline in this pandemic. I had no concerns in maintaining our protocols to keep both our team and our subjects safe, since she’s used to taking care of some of the sickest patients we have in the hospital.