Worldwide, the incidence of lung disease in children is on the rise. Today, some type of bronchial condition affects nearly 750 children per 100,000, and many are diagnosed via computed tomography (CT) scans. As a diagnostic imaging tool, CT plays a critical, powerful role in detecting these problems, but capturing the pictures presents its own safety risks, particularly radiation exposure.

To date, there hasn’t been a way to evaluate regional lung function and ventilation in a quick, accurate way that doesn’t pose potential harm to pediatric patients. But Cincinnati Children’s, through the leadership of Jason Woods, PhD, director of the Center for Pulmonary Imaging Research, has pioneered a way to overcome those concerns.

With his team, Woods has developed a safer, faster, more precise method for pinpointing lung disease and evaluating treatment efficacy. This new strategy uses a hyperpolarized version of the noble gas xenon (Xe) with radiation-free magnetic resonance imaging (MRI).

The Xe MRI is a diagnostic test that helps us better understand where the problem spots are for pediatric patients. It can potentially guide us to the best treatment and help us determine whether a therapy is effective,” Woods says. “It’s a test that gives us 3D visualization, so we know better how to intervene with medications or procedures. This is a large step forward in assessing lung ventilation.”

Widespread use of the test could introduce a sea change in pediatric pulmonary care, he says. In fact, in part based on his team’s work and research, medical imaging company Polarean, LLC spearheaded approval from the US Food and Drug Administration (FDA). The agency recently greenlighted Xe MRI use in patients as young as 12 years old.

The Need for Xe MRI

For the past 150 years, pulmonologists have relied on the pulmonary function test to examine lungs and test lung function in patients with obstructive lung diseases, including cystic fibrosis, asthma, bronchiolitis obliterans and some interstitial lung diseases. The test is reliable, Woods says, but it’s neither specific nor precise.

Today, providers are looking for a test that makes it easier to detect a patient’s ventilation problems and to determine how well a treatment works. This is where the Xe MRI can be a game-changer.

The test measures three things:

• Lung ventilation
• Alveolar airspace size
• Gas exchange (how much of the xenon dissolves into the patient’s tissue and red blood cells)

“This technology gives us our first clinical opportunity to capture a detailed map of regional ventilation that we can use to assess disease severity and precisely detect where changes get worse over time or where they change and improve with treatment,” he explains. “In a landscape of increasingly personalized pharmaceuticals, we believe this will allow both the patient and provider to understand these changes, improving care delivery.”

How Xe MRI Works

To develop the test, Woods’ team applied a complicated laser to a xenon gas mixture. Doing so creates hyperpolarization—it changes how the nucleus of the atom spins, triggering xenon’s magnetic properties. That magnetic signature allows the MRI machine to capture images without radiation.

From there, Xe is similar to contrast frequently used with MRI—with one distinct difference: It’s inhaled rather than injected. After a few resting breaths, the patient inhales Xe gas. Then, over the next 10 seconds, the MRI captures pictures of where the gas travels through the lungs.

What Xe MRI Can Reveal

Using this test can reveal various types of information about regional lung ventilation, depending on the pediatric patient’s condition:

• Cystic fibrosis—For children with this condition, the test helps pulmonologists determine treatment efficacy. Additionally, it can reveal whether a patient has early ventilation abnormalities, potentially indicating areas of more rapid decline.
• Asthma—An Xe MRI can help providers assess how well specific biologic treatments work for these patients.
• Bronchiolitis obliterans—The test can pinpoint early signs of any regional obstruction via ventilation either after lung transplant or bone marrow transplant. Quicker detection allows doctors to intervene faster to prevent the disease from developing further.

The Advantages for Children

Xe MRI testing works well for all patients with lung disease. But, Woods says, it offers three significant benefits to children:

• No radiation exposure that could potentially harm a child’s growing body
• Short 10-second test duration with no need to sit still for a long time
• Precision and accuracy, eliminating the need for repeat imaging

“This can change the way we actually perform MRIs if we want it to,” he says.

Cincinnati Children’s Leadership

Woods began his Xe investigations more than 20 years ago, but Cincinnati Children’s official leadership with the use of Xe MRI began in 2015 with the launch of the Xenon-129 MRI Clinical Trials Consortium. As the lead institution for this international group of 13 clinical research centers, Cincinnati Children’s spearheads the research and education efforts that explore Xe MRI’s potential capabilities.

“The Consortium has begun to standardize protocols that have led to clinical trials,” Woods says. “This work will also lead to improvements in medications and outcomes going forward.”

In fact, their work with pediatric patients has already led the clinical paradigm shift—FDA approval of Xe MRI in patients ages 12 years and up. For example, one 2020 study highlighted the high image quality and sensitivity of Xe MRI in detecting early airway obstruction in patients who have cystic fibrosis. Another 2021 study revealed the test’s ability to determine asthma severity and the efficacy of oral corticosteroid treatment.

Next Steps for Xe MRI

As encouraging as the recent FDA approval is, there’s still more work ahead to make Xe MRI a standard pulmonary diagnostic test, Woods says.

In the coming years, the Consortium joins Woods’ team at Cincinnati Children’s with three goals:

• Achieve FDA approval of Xe MRI for gas exchange and alveolar airspace size measurements
• Encourage the FDA to approve test use in children under 12 years of age
• Promote wider implementation among pulmonologists, cardiologists and radiologists

Ultimately, Woods says, patient and family buy-in will play a significant role in achieving those goals.

“Having patients and their families in the loop so they can see the testing and the images is critical. These images speak very loudly when you can see the problem or its resolution,” he says. “It makes a big emotional difference in their outlook, and it shows that this is such a great development for kids.”