Hyperpolarized Xenon MRI for Infant Lung Imaging

Recruiting at 1 trial location

Overseen By Carrie Stevens

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: Sedatives, Vasodilators, Inotropes, others

Disqualifiers: ECMO, Respiratory infection, Heart disease, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

12 Participants Needed

Trial Summary

What is the purpose of this trial?

Abnormalities of the lungs are common in newborns and can include aspiration or infectious pneumonia, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), congenital diaphragmatic hernia (CDH), and other abnormalities of lung development. Diagnostic radiography is commonly used in this population to differentiate diagnosis and to assess changes after treatment. While X-ray and CT provide quality imaging, they also expose infants to ionizing radiation. MR imaging offers a safe, non-ionizing alternative. However, imaging lungs via 1H MR is intrinsically difficult due to multiple air-tissue interfaces within the lungs causing local gradients and severe magnetic field susceptibility, which leads to an exceedingly short effective transverse relaxation time (T2\*). Additionally, the lungs have low proton density, which along with the short T2\* results in low signal to noise ratio, and the physiological motion caused by respiration and cardiac pulsation further reduces lung signal. The development of more powerful hardware, along with faster MRI techniques, has enabled detailed noninvasive 1H MR imaging of pulmonary tissues. Additionally, the development of inhaled hyperpolarized gas MRI has led to breakthroughs in the ability to visualize and quantify regional ventilation and alveolar size.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications. However, it does exclude those who have had general anesthesia within 24 hours or sedation like morphine, Versed, or fentanyl within the last 4 hours.

What data supports the effectiveness of the treatment Xenon Xe-129 for infant lung imaging?

Research shows that hyperpolarized Xenon-129 MRI is a promising method for imaging lung function, providing detailed images of lung ventilation and physiology. It has been used successfully in both children with cystic fibrosis and in preterm infants with lung conditions, indicating its potential effectiveness in assessing lung health in infants. ^{1 2 3 4 5}

Is hyperpolarized Xenon MRI safe for use in humans?

Research shows that hyperpolarized Xenon MRI has been evaluated for safety and tolerability in both healthy volunteers and patients with conditions like cystic fibrosis and chronic obstructive pulmonary disease. These studies suggest it is generally safe for use in humans, including children. ^{2 3 6 7 8}

What makes hyperpolarized 129Xe MRI unique for infant lung imaging?

Hyperpolarized 129Xe MRI is unique because it allows for detailed imaging of both lung ventilation and gas transfer, which is not possible with traditional imaging methods. This technique uses a special form of xenon gas that is hyperpolarized to enhance the MRI signal, providing clearer images of lung function and structure, even at low concentrations. ^{1 4 5 8 9}

Research Team

Jason Woods, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for infants aged 0-6 months in the NICU who need a bit more breathing support but are stable enough to undergo MRI, without severe heart disease, genetic issues affecting lung development, or recent surgery. They should not have had anesthesia recently and must fit into the NICU MRI scanner.

Inclusion Criteria

My oxygen levels stay above 88% with nasal oxygen support.

I am under 6 months old.

I am a stable NICU patient who can safely undergo an MRI.

Exclusion Criteria

I need medication to widen my blood vessels.

I have an irregular heartbeat that is not under control.

I have genetic issues that could affect my lung development.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Infants undergo hyperpolarized 129Xe MR lung imaging with a brief hypoxic challenge in a controlled setting

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• 129Xe

Trial Overview The study tests hyperpolarized Xenon (129Xe) as an MR imaging agent to visualize infant lung function safely without ionizing radiation. It aims to improve diagnosis and treatment assessment for various lung conditions in newborns.

Participant Groups

Group I: Oxygen with nasal cannula Experimental Treatment 1 Intervention

6 infants on oxygen with nasal cannula

Group II: HFNC, CPAP, or RAM cannula Experimental Treatment 1 Intervention

6 infants currently requiring respiratory support with high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) or RAM cannula

129Xe is already approved in United States for the following indications:

Approved in United States as Xenoview for:

• Evaluation of lung ventilation in adults and pediatric patients aged 12 years and older

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Findings from Research

The continuous flow-type hyperpolarizing (CF-HP) system allows for effective lung imaging using hyperpolarized (129)Xe MRI at very low concentrations of xenon, minimizing the anesthetic effects and reducing xenon consumption.

Using a 70% xenon gas mixture resulted in better signal-to-noise ratios for both gas and dissolved-phase images compared to a 3% mixture, although the apparent diffusion coefficient (ADC) was higher with the 3% mixture, indicating a complex relationship between concentration and imaging quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 129 Xe MRI of the mouse lung at a low xenon concentration using a continuous flow-type hyperpolarizing system. Wakayama, T., Kitamoto, M., Ueyama, T., et al.[2015]

Hyperpolarized 129Xe gas is safe and well-tolerated as an inhaled contrast agent for MRI in children, with no serious adverse events reported during the study involving 28 participants aged 6 to 16 years.

While some children experienced mild and temporary changes in oxygen saturation and heart rate after inhalation, these effects were consistent with expected physiological responses and resolved quickly, indicating that 129Xe MRI is feasible for assessing lung function in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. Walkup, LL., Thomen, RP., Akinyi, TG., et al.[2022]

Hyperpolarized 129 Xe MRI has shown promise in assessing lung function in neonates with bronchopulmonary dysplasia (BPD), demonstrating good image quality and sensitivity to detect mild ventilation abnormalities in a small study of 9 patients.

The study found elevated apparent diffusion coefficients (ADCs) in BPD patients compared to healthy individuals, indicating potential lung microstructural changes, and a low red blood cell to tissue membrane signal ratio, suggesting altered gas exchange in these infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial feasibility and challenges of hyperpolarized 129 Xe MRI in neonates with bronchopulmonary dysplasia. Stewart, NJ., Higano, NS., Mukthapuram, S., et al.[2023]

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]

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]

Inhalation of hyperpolarized xenon-129 (129Xe) was found to be safe and well tolerated among 44 subjects, including healthy individuals and patients with chronic obstructive pulmonary disease (COPD), with no serious adverse events reported.

While 91% of participants experienced mild and transient symptoms such as dizziness and euphoria, these symptoms resolved quickly without the need for clinical intervention, indicating that the procedure is generally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. Driehuys, B., Martinez-Jimenez, S., Cleveland, ZI., et al.[2022]

In a study involving 37 children with asthma and healthy controls, hyperpolarized 129Xe MRI revealed that children with asthma had significantly higher ventilation defect percentages (VDP) and more defects per image slice compared to healthy peers, indicating that this imaging technique can effectively identify lung ventilation issues in pediatric asthma.

The study found that higher VDP and defect counts were associated with increased health care utilization and oral corticosteroid use, suggesting that 129Xe MRI could serve as a valuable biomarker for assessing asthma severity and predicting exacerbation risk in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

129Xe MRI as a measure of clinical disease severity for pediatric asthma. Lin, NY., Roach, DJ., Willmering, MM., et al.[2023]

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]

References

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

Hyperpolarized 129 Xe MRI of the mouse lung at a low xenon concentration using a continuous flow-type hyperpolarizing system. [2015]

2. Germany pubmed.ncbi.nlm.nih.gov

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. [2022]

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

Initial feasibility and challenges of hyperpolarized 129 Xe MRI in neonates with bronchopulmonary dysplasia. [2023]

4. Ireland pubmed.ncbi.nlm.nih.gov

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

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

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

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

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. [2022]

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

129Xe MRI as a measure of clinical disease severity for pediatric asthma. [2023]

8. Australia pubmed.ncbi.nlm.nih.gov

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]