Hyperpolarized Xenon MRI for Lung Transplant Rejection

Recruiting at 1 trial location

Overseen By Jane Park

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Xemed LLC

Disqualifiers: Pregnancy, Implanted metal device, others

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

Compensation: Varies

Number of Visits: 6

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will use Magnetic Resonance Imaging (MRI) to study the lungs of 90 volunteers using the inhaled contrast agent, hyperpolarized xenon-129. Once inhaled, this gas can provide information to imagers regarding lung functionality across specific regions of the lungs by assessing the replacement of air during the normal breathing cycle, how much oxygen is in the airspaces, and if the natural spongy tissue structure has been compromised by lung disease. Of the 90 subjects, 70 will be patients who received lung transplantation from the Penn/Temple Lung Transplant Teams and are receiving follow up treatment at HUP or TUH, 10 will be healthy control subjects who participated favorably in our HP 129Xe imaging protocol, and 10 will be patients who have been diagnosed with chronic obstructive pulmonary disease (COPD)-preferentially recruited from the Temple University COPDGene cohort, who have never undergone a lung transplant. 20 of the lung transplant recipient subjects will be patients who have received a recent clinical diagnosis of chronic lung allograft dysfunction (CLAD) prior to enrollment in our study, while the other 50 will have recently undergone their initial transplant surgery at the time of enrollment.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Hyperpolarized 129-Xenon (MagniXene) MRI for lung transplant rejection?

Research shows that hyperpolarized gas MRI, like the one using 129-Xenon, is a promising tool for lung imaging because it can detect early changes in lung function that other methods might miss. This technology has been used successfully in other lung conditions, suggesting it could be effective for monitoring lung transplant rejection. ^{1 2 3 4 5}

Is Hyperpolarized Xenon MRI safe for humans?

Research shows that inhaling hyperpolarized xenon 129 (a special form of xenon gas) for MRI is generally safe and well-tolerated in both healthy volunteers and patients with conditions like chronic obstructive pulmonary disease. Studies have also explored its use in children, indicating it is a promising and safe method for lung imaging. ^{6 7 8 9 10}

How is hyperpolarized xenon MRI different from other treatments for lung transplant rejection?

Hyperpolarized xenon MRI is unique because it uses a special form of xenon gas to create detailed images of the lungs, allowing doctors to assess both ventilation and gas transfer. This imaging technique is non-invasive and provides insights into lung function that are not possible with traditional imaging methods. ^{5 11 12 13 14}

Research Team

Maxim Itkin, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for children and young adults aged 8-20 who have had a lung transplant. They must be able to perform a pulmonary function test and not be pregnant, severely claustrophobic, or have any metal implants that could interfere with MRI safety.

Inclusion Criteria

I am between 8 and 20 years old.

Available clinically indicated pulmonary function test

You have had a lung transplant in the past.

Exclusion Criteria

Any contraindication to the safe performance of MRI (metallic foreign bodies, non-safety rated implanted devices including but not limited to vascular clips, pacemaker, stent, infusion pump, neuro-stimulator, prosthesis)

I need medication to help me relax or sleep for medical procedures.

I cannot perform a lung function test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Baseline imaging session using hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung at 3 months post-transplant

1-2 hours

1 visit (in-person)

Follow-up Imaging

Follow-up imaging sessions using hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung at 6, 9, 12, 18, and 24 months post-transplant

up to 2 years

5 visits (in-person)

Data Analysis

Examine correlations between pulmonary function test scores and MRI metrics

End of the project

Treatment Details

Interventions

• Hyperpolarized 129-Xenon (MagniXene) MRI of the lung

Trial Overview The study tests the use of Hyperpolarized 129-Xenon (MagniXene) MRI to assess chronic lung allograft dysfunction (CLAD) in pediatric patients post-lung transplant. It aims to provide better imaging without radiation risks associated with CT scans.

Participant Groups

Group I: Post-lung transplant patients not diagnosed with CLAD Experimental Treatment 1 Intervention

This group will have a target enrollment of 50 subjects recruited from the lung transplant patients of pulmonologists from Penn and Temple Lung Transplant Team. The subjects will undergo hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung at 3, 6, 9, 12, 18, and 24 months following the transplant. Additional pulmonary tests and questionnaires will be performed to assess the lung health status of the patients.

Group II: Post-lung transplant patients diagnosed with CLAD Experimental Treatment 1 Intervention

This group will have a target enrollment of 20 subjects recruited from the lung transplant patients of pulmonologists from Penn and Temple Lung Transplant Team, and whom have been recently diagnosed with CLAD. The subjects will undergo a single imaging session of hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung.

Group III: Non-transplant COPD patients Experimental Treatment 1 Intervention

This group will have a target enrollment of 10 subjects recruited from the pool of advanced stages of COPD visiting patients from Penn and Temple pulmonologists. The subjects will undergo two imaging sessions of hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung within approximately week to ensure imaging metric reproducibility.

Group IV: Healthy control subjects Experimental Treatment 1 Intervention

This group will have a target enrollment of 10 subjects recruited from general population and not suffering from any chronic lung diseases. The subjects will undergo two imaging sessions of hyperpolarized 129-Xenon MRI and conventional proton MR imaging of the lung within approximately week to ensure imaging metric reproducibility.

Who Is Running the Clinical Trial?

Xemed LLC

Lead Sponsor

Trials

8

Recruited

370+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Findings from Research

Dynamic 3He-MRI effectively distinguished between normal lung grafts and diseased native lungs in single lung transplant recipients, indicating its potential for assessing lung health post-transplant.

However, the technique was unable to differentiate between normal and rejected grafts in double lung transplant recipients, suggesting limitations in its application for monitoring graft rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distribution of ventilation in lung transplant recipients: evaluation by dynamic 3He-MRI with lung motion correction. Gast, KK., Puderbach, MU., Rodriguez, I., et al.[2015]

In a study involving 30 mice, magnetization transfer (MT) imaging was able to distinguish between healthy lungs and those experiencing acute rejection (AR) after transplantation, showing significant differences in magnetization transfer ratio (MTR) values (P = 0.007).

The largest differences in MTR were observed at specific off-resonance frequencies, indicating that MT measurements could serve as a valuable quantitative tool for assessing AR in lung transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetization transfer as a potential tool for the early detection of acute graft rejection after lung transplantation in mice. Kenkel, D., Yamada, Y., Weiger, M., et al.[2022]

Quantitative non-contrast-enhanced MRI shows a strong correlation with CT imaging and spirometry results in assessing ventilation impairment in lung transplant patients, indicating its potential as a reliable non-ionizing imaging method.

The study, involving 10 lung-transplanted patients, found that MRI effectively classified lung conditions such as low ventilation and air trapping, suggesting it could be used for ongoing monitoring of lung transplant recipients without the risks associated with ionizing radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Multivolume Proton-Magnetic Resonance Imaging in Lung Transplant Recipients: Comparison With Computed Tomography and Spirometry. Pennati, F., Salito, C., Borzani, I., et al.[2021]

Dynamic contrast-enhanced MR imaging can effectively detect pulmonary perfusion defects in patients with unilateral lung transplantation, as demonstrated in a study involving five transplant patients and nine healthy controls.

The study found that after contrast administration, healthy lungs showed a significant increase in signal intensity, while the native lung in transplant patients exhibited clear perfusion defects, confirmed by additional scintigraphy, indicating that most blood flow is directed to the transplanted lung.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung perfusion demonstrated by contrast-enhanced dynamic magnetic resonance imaging. Application to unilateral lung transplantation. Berthezène, Y., Croisille, P., Bertocchi, M., et al.[2019]

Hyperpolarized gas MRI is a promising non-invasive imaging technique that can effectively diagnose early lung function deterioration, overcoming challenges faced by traditional proton-based MRI due to short T2* times and low proton density in lung tissue.

This review highlights various applications of hyperpolarized gas MRI, including ventilation imaging and oxygen-pressure mapping, which enhance its diagnostic capabilities compared to other MRI methods and could significantly improve lung disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized gas MRI in pulmonology. Kern, AL., Vogel-Claussen, J.[2020]

A portable xenon-129 (129Xe) hyperpolariser was successfully designed and built, allowing for clinically accessible lung MRI without the need for external utilities, making it easy to transport and set up in hospital settings.

The system was tested by transporting it 200 km to a hospital, where it produced high-quality 129Xe MR images within a day of installation, demonstrating its feasibility for multicentre clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standalone portable xenon-129 hyperpolariser for multicentre clinical magnetic resonance imaging of the lungs. Norquay, G., Collier, GJ., Rodgers, OI., et al.[2023]

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]

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]

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]

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 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]

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]

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]

References

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

Distribution of ventilation in lung transplant recipients: evaluation by dynamic 3He-MRI with lung motion correction. [2015]

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

Magnetization transfer as a potential tool for the early detection of acute graft rejection after lung transplantation in mice. [2022]

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

Quantitative Multivolume Proton-Magnetic Resonance Imaging in Lung Transplant Recipients: Comparison With Computed Tomography and Spirometry. [2021]

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

Lung perfusion demonstrated by contrast-enhanced dynamic magnetic resonance imaging. Application to unilateral lung transplantation. [2019]

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

Hyperpolarized gas MRI in pulmonology. [2020]

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

Standalone portable xenon-129 hyperpolariser for multicentre clinical magnetic resonance imaging of the lungs. [2023]

7. 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]

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

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

9. 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]

10. 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]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]

12. Australia pubmed.ncbi.nlm.nih.gov

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

13. Ireland pubmed.ncbi.nlm.nih.gov

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

14. 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]