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Hello, hyperpolarized helium MRI
May 2017
by Ilene Schneider  |  Email the author
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COLUMBIA, Mo.—According to the Cystic Fibrosis Foundation, more than 30,000 Americans are living with cystic fibrosis (CF), which has no cure. While a drug approved by the U.S. Food and Drug Administration treats the underlying cause of the disease, its effectiveness for each individual is unknown. Researchers from the University of Missouri School of Medicine, who have developed an imaging technique using a specific form of helium to measure the drug’s effectiveness, hope their findings might lead to improved therapies for CF and other lung conditions.
 
“People with cystic fibrosis have an imbalance of salt in their bodies caused by the defective CFTR protein,” said Dr. Talissa Altes, chair of the Department of Radiology at the MU School of Medicine and lead author of the study. “The drug ivacaftor targets this defective protein, but to what extent it is successful is not well understood. Our study sought to use a new way of imaging the lung to understand how well the drug is working in patients with a specific gene mutation known as G551D-CFTR.”
 
The study, “Use of Hyperpolarized Helium-3 MRI to Assess Response to Ivacaftor Treatment in Patients with Cystic Fibrosis,” was published in the Journal of Cystic Fibrosis. The research was supported by Vertex Pharmaceuticals Inc., the manufacturer of ivacaftor, as well as by the Hartwell Foundation and Siemens Healthcare.
 
As Altes explained, ivacaftor is the first approved drug that corrects the defective protein in CF, a transmembrane chloride channel (CFTR). There are more than 1,500 different mutations of the CF gene. The patients in this study had a particular mutation, G551D. In patients with this mutation, the chloride channel is made, folded and transported to the cell surface but it does not open normally. Ivacaftor is a small molecule that opens the defective chloride channel. Prior to the development of ivacaftor, treatments for CF revolved around preventing and treating infection and improving airway mucus clearance. Ivacaftor is the first approved drug of a new class of drugs: the CFTR potentiators.
 
“The most commonly used method to assess lung function is spirometry,” Altes said. “With spirometry, patients blow out all of the air from their lungs as hard and fast as they can. The airflow is measured at the mouth and compared with normative values. Spirometry is known to be insensitive to early lung disease and small changes in disease severity. Further, it is effort dependent. This method is not well suited for pediatric patients, because it requires concentration, controlled breathing and cooperation with the spirometry technician.”
 
She added, “Hyperpolarized helium-3 MRI (helium MRI) uses an inhaled gaseous contrast agent (helium-3) to image the lung in 3-D. Areas of the lung that are well ventilated appear bright and areas that are poorly ventilated appear dark on the helium MR images. By looking at the regional lung ventilation, our hypothesis was that helium MRI would be more sensitive to small changes in disease severity than spirometry, which assesses global airflow at the mouth. All patients who improved with treatment on spirometry also improved on helium MRI. Further, we were able to detect improvement in lung ventilation on helium MRI in patients who had little change in spirometry on treatment. Although our study was too small to prove this hypothesis, it is encouraging.”
 
According to Altes, patients with CF and G551D mutation have shown improvements in lung function on spirometry in prior studies and improvements in lung ventilation on helium MRI in her study. She did note that “It is too early to know whether this will translate into a longer life expectancy, but the community is hopeful. The expectation is that by treating the underlying molecular issue in CF, treatment with ivacaftor will extend the lives of patients with CF.” 
 
She added that Polarean is about to begin a Phase 3 clinical trial for a similar gaseous contrast agent for MRI, hyperpolarized xenon-129. Similar ventilation abnormalities can be demonstrated with either contrast agent. Xenon-129 is more naturally abundant than helium-3, so it is likely to be used clinically. Helium-3 may be used more in research.
 
“More drugs are under development to treat cystic fibrosis and other lung conditions, and improved imaging techniques are needed to test their effectiveness,” Altes concluded. “The importance of this technique is that it may well be a cost-effective tool to aid in the development of these drugs. However, it also can help patients know which medications may work best for their unique conditions.”
 
Code: E051720

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