MRI-based assessments could help guide timely interventions
People with cystic fibrosis (CF) frequently develop bronchiectasis— severe airway dilation—in early childhood. This pathological structural remodeling, and the underlying processes that drive it, are widely thought to be irreversible. But what if they weren’t?
Physical chemist Zackary Cleveland, PhD, associate director of the Cincinnati Children’s Center for Pulmonary Imaging Research, is investigating whether that is truly the case—or if there may be a way to avoid life-long problems. To find out, he’s exploiting the sensitivity and radiation-free nature of hyperpolarized xenon gas and ultra-short echo-time (UTE) MRI to monitor how structural abnormalities like bronchiectasis and associated functional losses affect patients over time.
“While people quibble over quantitative definitions, bronchiectasis is an easy thing to identify using the long-time clinical standard for lung imaging, CT. However, the utility of these definitions is questionable. Pathology is irreversible if you watch it long-term and it doesn’t reverse,” he says. “This is where our emerging MRI technologies come into play. We can evaluate our pediatric patients regularly without any safety concerns.”
Changes to Cystic Fibrosis Care
The introduction of elexacaftor, a new medication for patients with CF, revolutionized how providers treat this chronic condition. The drug targets protein dysfunction caused by F508del, the most common CF genetic mutation. In doing so, it improves quality of life, increases lung function and extends life for approximately 90% of patients.
With CF patients now living longer, it’s best to keep closer tabs on them if they also have bronchiectasis or another lung-related complication. Damage to their airways increases their chances of inflammation and infection. Advanced imaging is the easiest way to observe any emerging changes. CT scans provide the most detailed structural pictures, but they also expose children to radiation and provide not functional information.
“No one wants to irradiate children, particularly now that they are expected to live into their 70s. They are growing, and those rapidly dividing cells are more susceptible to radiation,” Cleveland says. “MRI—which is radiation free—has a real advantage because we can image these patients as frequently as we can afford with no safety concerns.”
Watching these changes over time as patients age from pediatric to adult and ultimately to geriatric cases could reveal early details about emerging pathology that takes time to manifest clinically. With that information, investigators might develop ways to reduce or sidestep negative outcomes.
Monitoring with MRI
Cleveland and his collaborators are working with patients between the ages of 7 and 21 years to test how well xenon gas and MRI track the long-term progression of lung conditions, such as bronchiectasis. Xenon is a noble gas that doesn’t exist inside the body, so it’s easy to track where it goes on imaging. Several other Cincinnati Children’s researchers also use this technique in their investigations across a range of lung diseases.
After taking a few practice breaths, patients inhale a small amount of xenon and hold their breath during the 10-second MRI scan. These images reveal where the gas distributes in the alveoli, how much dissolves into the blood-air barrier, and how much diffuses into red blood cells. The scans also allow Cleveland and his team to noninvasively measure the size of alveoli in the lungs, revealing incremental microstructural changes.
“With each image, we can detect alveolar size increases that happen with normal aging and with pathological processes,” he says. “These images allow us to monitor small changes in existing abnormalities and identify new pathology that is invisible using standard clinical tools.”
The Value of Tracking Changes
According to Cleveland, no one has monitored CF-related microstructural alveolar damage in the past. The life expectancy of patients with CF was too short and other pathology was too severe. However, tracking changes now could make a difference in treatment strategies and patient outcomes.
“With this functional and structural imaging, we could potentially detect subtle changes early. Based on what the provider sees, they could treat antibiotics or anti-inflammatories—the standard pharmacy approaches,” he says. “This is important for patients, particularly as they move into middle age. There’s potential for a completely new lung disease to take hold because they’ve spent their first decades of life with their lungs half inflamed.”
For example, he explains, many CF patients have emphysema-like characteristics on MRI. Currently, symptoms are subclinical, but it’s unclear if they will develop into more significant problems when patients reach their 50s or 60s. Imaging data collected over years could provide answers that improve patient well-being.
Ultimately, Cleveland says, these hyperpolarized xenon MRI scans may help providers prepare for treating patients with CF in the future.
“The landscape of this disease has changed so dramatically,” he says. “We need to start understanding what current subclinical pathology is going to manifest 20 years from now so we can get out ahead of it.”
(Published December 2023)
