Xenon-129 MRI for Thoracic Insufficiency Syndrome

Overseen By Samantha Gogel

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Patrick Cahill, MD

Disqualifiers: Not diagnosed with TIS

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 2 years

15 Participants Needed

Trial Summary

What is the purpose of this trial?

Thoracic insufficiency syndrome (TIS) is a complex condition that involves chest wall deformities that can affect normal breathing and lung growth. In most cases, children with TIS are also born with spine disorders such as scoliosis. The inability of the thorax to support normal respiration or lung growth can cause respiratory distress and even mortality. Investigators aim to validate MRI imaging sequences to use as an assessment tool for pulmonary function.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Xenon-129 MRI for Thoracic Insufficiency Syndrome?

Research shows that Xenon-129 MRI is effective in assessing lung function and physiology in conditions like pulmonary fibrosis and pediatric lung diseases. This suggests it could be useful for evaluating lung issues in Thoracic Insufficiency Syndrome as well. ^{1 2 3 4 5}

Is Xenon-129 MRI safe for humans?

MRI, including Xenon-129 MRI, is generally considered safe for humans, but there are some safety concerns such as potential allergic reactions to contrast agents, effects of magnetic fields, and psychological effects like claustrophobia. Guidelines and safety practices are in place to minimize these risks. ^{6 7 8 9 10}

How does Xenon-129 MRI differ from other treatments for Thoracic Insufficiency Syndrome?

Xenon-129 MRI is unique because it uses hyperpolarized xenon gas to create detailed images of lung function and structure, which can help assess ventilation and gas transfer in the lungs. This imaging technique is different from other treatments as it provides a non-invasive way to evaluate lung function and may be particularly useful in managing conditions affecting lung structure and function. ^{2 11 12 13 14}

Research Team

Patrick Cahill, MD

Principal Investigator

Children's Hopsital of Philadelphia

Eligibility Criteria

This trial is for boys and girls aged 6 to 18 who have been diagnosed with Thoracic Insufficiency Syndrome (TIS) and are scheduled for surgery. It's not open to those without a TIS diagnosis.

Exclusion Criteria

I do not have thoracic insufficiency syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo MRI imaging sequences to assess pulmonary function

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MRI Imaging
• Xenon-129

Trial Overview The study is testing the use of Xenon-129 in MRI imaging sequences as a new way to assess lung function in patients with TIS, which often includes chest wall deformities and spine disorders like scoliosis.

Participant Groups

Group I: Thoracic Insufficiency Group Experimental Treatment 1 Intervention

Thoracic insufficiency syndrome patients undergoing surgery

Who Is Running the Clinical Trial?

Patrick Cahill, MD

Lead Sponsor

Trials

1

Recruited

20+

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Xemed LLC

Industry Sponsor

Trials

8

Recruited

370+

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]

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]

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]

Magnetic resonance imaging (MRI) using hyperpolarised gases like helium-3 and xenon-129 allows for detailed structural and functional assessments of the lungs without the risks associated with ionising radiation, making it particularly suitable for pediatric patients.

This imaging technique is crucial for understanding and treating chronic lung diseases such as asthma and cystic fibrosis, which are common in children and currently have significant unmet therapeutic needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary functional magnetic resonance imaging for paediatric lung disease. Kirby, M., Coxson, HO., Parraga, G.[2013]

This case report highlights an allergic reaction to Gadolinium-DTPA, a contrast agent used in MRI scans, occurring upon the first exposure, emphasizing the need for awareness of potential allergic responses.

The report includes a review of the safety profile of MR contrast agents, suggesting that while they are generally safe, individual reactions can occur, warranting careful monitoring during their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute allergic reaction upon first exposure to gadolinium-DTPA: a case report. Rahman, SL., Harbinson, MT., Mohiaddin, R., et al.[2019]

Magnetic resonance (MR) imaging is a safe diagnostic method, as it does not pose hazards to patients or medical personnel from the magnetic fields used during the procedure.

The study addresses concerns about the safety of permanent, gradient, and electromagnetic fields in MR tomography, concluding that these factors do not present significant risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of patients and personnel at a department of MR tomography, a new method of imaging in medicine]. Gomet, B.[2015]

Over a 10-year period, the FDA received 1568 reports of adverse events related to magnetic resonance (MR) systems, with 1548 reports analyzed, highlighting the importance of monitoring safety in MR imaging.

The most common serious injuries reported were thermal events, accounting for 59% of cases, followed by mechanical events (11%), projectile events (9%), and acoustic events (6%), indicating specific risks associated with MR environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-related FDA adverse event reports: A 10-yr review. Delfino, JG., Krainak, DM., Flesher, SA., et al.[2020]

The study identifies eight key safety concerns related to clinical magnetic resonance (MR) imaging, including risks from the static magnetic field, potential projectile effects, and the impact of radio-frequency fields.

Specific issues such as noise-induced auditory effects, psychological impacts like claustrophobia, and safety considerations regarding the use of contrast agents are highlighted, emphasizing the need for awareness and management of these risks during MR imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety considerations in MR imaging. Kanal, E., Shellock, FG., Talagala, L.[2013]

The American College of Radiology's updated guidance document on MR safety emphasizes the importance of addressing new risks and adverse events in the MR environment, ensuring safer practices for patients and personnel.

The latest recommendations include mandatory annual MR safety training for medical directors, highlighting the need for continuous education to adapt to evolving safety concerns in clinical and research settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACR guidance document on MR safe practices: Updates and critical information 2019. Greenberg, TD., Hoff, MN., Gilk, TB., et al.[2021]

High-quality MRI of lung ventilation can be achieved using naturally abundant xenon (NAXe) gas, demonstrating its potential as a cost-effective imaging agent for pulmonary studies.

The study showed that NAXe MRI provided comparable image quality to enriched xenon and helium-3 (3He) imaging, with the ability to detect minor ventilation defects, particularly in a healthy smoker's lungs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of human lung ventilation imaging using highly polarized naturally abundant xenon and optimized three-dimensional steady-state free precession. Stewart, NJ., Norquay, G., Griffiths, PD., 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 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]

A new imaging technique allows for simultaneous acquisition of lung images using two hyperpolarized gases, helium-3 and xenon-129, along with anatomical proton images in a single breath hold, enhancing the efficiency of lung imaging.

This method provides high-quality, spatially and temporally registered images that combine functional and structural information about the lungs, which could improve diagnostic capabilities in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous imaging of lung structure and function with triple-nuclear hybrid MR imaging. Wild, JM., Marshall, H., Xu, X., et al.[2022]

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. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

Pulmonary functional magnetic resonance imaging for paediatric lung disease. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Acute allergic reaction upon first exposure to gadolinium-DTPA: a case report. [2019]

7. Poland pubmed.ncbi.nlm.nih.gov

[Safety of patients and personnel at a department of MR tomography, a new method of imaging in medicine]. [2015]

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

MRI-related FDA adverse event reports: A 10-yr review. [2020]

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

Safety considerations in MR imaging. [2013]

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

ACR guidance document on MR safe practices: Updates and critical information 2019. [2021]

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

Feasibility of human lung ventilation imaging using highly polarized naturally abundant xenon and optimized three-dimensional steady-state free precession. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]

13. Australia pubmed.ncbi.nlm.nih.gov

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

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

Simultaneous imaging of lung structure and function with triple-nuclear hybrid MR imaging. [2022]