Xenon-129 MRI for Pulmonary Disease

Overseen By Sharon Braganza, BSc

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: The Hospital for Sick Children

Disqualifiers: Cardiovascular disorders, Respiratory infection, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment Xenon-129 MRI for Pulmonary Disease?

Research shows that hyperpolarized Xenon-129 MRI is a promising tool for imaging lung function, as it can effectively measure lung ventilation and detect impaired lung physiology in conditions like pulmonary fibrosis. This imaging technique has been standardized and is well-tolerated by both healthy individuals and those with lung diseases. ^{1 2 3 4 5}

How does the treatment using Xenon-129 MRI differ from other treatments for pulmonary disease?

Xenon-129 MRI is unique because it uses hyperpolarized xenon gas to create detailed images of lung function, allowing doctors to see both ventilation and gas exchange in the lungs. This imaging technique is different from other treatments as it provides a non-invasive way to assess lung function and detect issues like ventilation-perfusion mismatch, which is not possible with standard imaging methods. ^{1 2 6 7 8}

What is the purpose of this trial?

Aim of this study is to evaluate image quality and reproducibility of Xenon-129 and Inert fluorinated (19F) gas Magnetic Resonance Imaging (MRI) and to evaluate changes in lung structure and function in participants with cystic fibrosis (CF) and asthma compared to healthy controls.

Research Team

Giles Santyr, PhD

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

This trial is for healthy individuals and those with cystic fibrosis or asthma, aged 8 and older, who have never smoked and can hold their breath for at least 16 seconds. Participants must be able to perform consistent pulmonary function tests and not require supplemental oxygen. Those with severe heart conditions, mental incapacitation, recent respiratory infections, claustrophobia that prevents MRI scans, pregnancy or metal implants incompatible with MRI are excluded.

Inclusion Criteria

Participants have no smoking history.

Participants should have a FEV1%pred value greater than 40%.

For participants with CF and asthma, a clinical diagnosis is necessary and they should be at their baseline level of symptom control based on history.

Exclusion Criteria

You have a history of heart problems like heart attacks, irregular heartbeats, or high blood pressure.

Participant is, in the opinion of the investigator, mentally or legally incapacitated, preventing informed consent/assent from being obtained, or cannot read or understand the written material

You have had a cold or respiratory infection in the past four weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo magnetic resonance imaging using hyperpolarized xenon-129 and inert fluorinated gases to evaluate lung function and structure.

1-2 weeks

1-2 visits (in-person)

Follow-up

Participants are monitored for changes in lung function and structure after imaging.

4 weeks

Treatment Details

Interventions

• Lung Clearance Index
• Magnetic Resonance Imaging
• Xenon-129

Trial Overview The study is testing the quality of lung images taken using Xenon-129 and Perfluoropropane (19F) gases in an MRI scan. It aims to compare these images between healthy volunteers and patients with cystic fibrosis or asthma to detect changes in lung structure and function.

Participant Groups

Group I: Healthy Active Control 3 Interventions

Healthy Participants ages 8 and older. Participants with inhale hyperpolarized xenon-129 which is used as a contrast agent for lung imaging. Perfluoropropane will also be used as a contrast agent for MRI. Perfluoropropane will be inhaled as a normoxic mixture (21% O2 and 79% perfluoropropane). Participants will undergo magnetic resonance imaging and lung clearance index.

Group II: Cystic Fibrisos Active Control 3 Interventions

Participants with cystic fibrosis ages 8 and older.Participants with inhale hyperpolarized xenon-129 which is used as a contrast agent for lung imaging. Perfluoropropane will also be used as a contrast agent for MRI. Perfluoropropane will be inhaled as a normoxic mixture (21% O2 and 79% perfluoropropane). Participants will undergo magnetic resonance imaging and lung clearance index.

Group III: Asthma Active Control 3 Interventions

Participants with asthma ages 8 and older.Participants with inhale hyperpolarized xenon-129 which is used as a contrast agent for lung imaging. Perfluoropropane will also be used as a contrast agent for MRI. Perfluoropropane will be inhaled as a normoxic mixture (21% O2 and 79% perfluoropropane). Participants will undergo magnetic resonance imaging and lung clearance index.

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Findings from Research

The study demonstrated that injecting hyperpolarized xenon-129 (129Xe) into the bloodstream of rats is a safe method that produces a strong signal in the lungs, allowing for effective imaging of pulmonary perfusion and gas exchange.

This technique revealed important insights, such as ventilation-perfusion deficits and temporary impairments in gas exchange due to saline overload, suggesting its potential as a sensitive and non-invasive tool for evaluating lung function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary perfusion and xenon gas exchange in rats: MR imaging with intravenous injection of hyperpolarized 129Xe. Driehuys, B., Möller, HE., Cleveland, ZI., et al.[2021]

A new continuous-flow system for producing hyperpolarized xenon (129Xe) has been developed, achieving production rates of 0.3 liters per hour with 64% polarization, significantly improving the availability of this imaging agent for lung MRI studies.

This technology allows for the production of multiliter quantities of hyperpolarized xenon several times daily, enabling more extensive human lung imaging studies that were previously limited by the availability of hyperpolarized gas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large production system for hyperpolarized 129Xe for human lung imaging studies. Hersman, FW., Ruset, IC., Ketel, S., et al.[2022]

The recent FDA approval of hyperpolarized 129Xe as an MR contrast agent highlights its growing importance in lung imaging, prompting the need for standardized techniques across research and clinical sites.

The 129Xe MRI Clinical Trials Consortium has established best practices for the entire workflow of 129Xe MRI, including safety monitoring and technical considerations, to ensure effective and safe imaging of lung ventilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation. Garrison, WJ., Mugler, JP., Mata, JF., et al.[2023]

Hyperpolarized xenon-129 MRI detected significant lung function impairments in patients with usual interstitial pneumonia (UIP), showing a ventilation defect fraction of 30% compared to 21% in healthy controls, indicating its efficacy in identifying lung abnormalities.

The MRI also revealed elevated levels of xenon dissolved in the lung interstitium in UIP patients, which could serve as an early indicator of lung fibrosis, even when traditional pulmonary function tests showed normal or mild impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Xenon-129: A New Tool to Assess Pulmonary Physiology in Patients with Pulmonary Fibrosis. Qing, K., Altes, TA., Mugler, JP., et al.[2023]

Inhalation of hyperpolarized (129)Xe gas was well tolerated among 42 participants, including healthy individuals and those with various pulmonary diseases, with only two mild adverse events reported, indicating a strong safety profile.

The study showed that while there were statistically significant changes in oxygen saturation and heart rate after inhalation, these changes were clinically insignificant and resolved quickly, suggesting that (129)Xe inhalation is safe for use in both healthy and diseased lungs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease. Shukla, Y., Wheatley, A., Kirby, M., et al.[2022]

Hyperpolarized 129 Xenon-MRI (HP 129 Xe MRI) is a new imaging technique that can assess both how well air moves in and out of the lungs (ventilation) and how effectively gases are transferred in the lungs.

While most studies have focused on non-cancer lung diseases, HP 129 Xe MRI shows great potential for improving the management and understanding of lung cancer by evaluating these key lung functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI. Song, EJ., Kelsey, CR., Driehuys, B., et al.[2022]

Hyperpolarized 129Xe MRI (HypX-MRI) shows great promise as a new diagnostic tool, enhancing the detectability of lung structures and potentially allowing for better imaging of lipid-rich tissues, which has been challenging with traditional methods.

This technique could help identify issues like ventilation-perfusion mismatch in pulmonary diseases and may also be used for functional MRI studies of the brain, opening new avenues for understanding lung function and brain perfusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. Albert, MS., Balamore, D.[2019]

Hyperpolarized (HP) noble gas MRI, particularly using 129Xe, has shown promising results in assessing lung ventilation and regional lung physiology, making it a potential game-changer in pulmonary medicine.

Despite being limited to select academic institutions currently, advancements in polarizer technology suggest that HP 129Xe MRI could soon become more widely available for clinical use, enhancing the diagnostic capabilities for lung conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of hyperpolarized 129xenon in MR imaging of pulmonary function. Ebner, L., Kammerman, J., Driehuys, B., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pulmonary perfusion and xenon gas exchange in rats: MR imaging with intravenous injection of hyperpolarized 129Xe. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Large production system for hyperpolarized 129Xe for human lung imaging studies. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Hyperpolarized Xenon-129: A New Tool to Assess Pulmonary Physiology in Patients with Pulmonary Fibrosis. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

The role of hyperpolarized 129xenon in MR imaging of pulmonary function. [2018]