Hyperpolarized Xenon MRI for Lung Transplant Rejection

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a special kind of MRI, using hyperpolarized xenon-129 gas, can enhance understanding of lung function. It includes lung transplant recipients, individuals diagnosed with chronic lung allograft dysfunction (CLAD), those with chronic obstructive pulmonary disease (COPD), and healthy individuals. The goal is to assess lung performance and identify issues in lung transplant patients. Ideal participants are lung transplant recipients from Penn or Temple hospitals, individuals with COPD who have never had a transplant, or healthy individuals without chronic lung diseases. As an unphased study, this trial allows participants to contribute to groundbreaking research that could improve lung health diagnostics.

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 prior data suggests that hyperpolarized xenon-129 MRI is safe for lung imaging?

Research has shown that inhaling hyperpolarized xenon-129, the gas used in this MRI study, is safe for people. In one study, 44 participants, including both healthy individuals and those with lung problems, inhaled this gas without major issues. Participants tolerated the treatment well, experiencing no significant side effects. This suggests the gas is generally safe for lung imaging. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using hyperpolarized 129-Xenon MRI because it offers a fresh way to look at lung function and detect transplant rejection early. Unlike standard imaging methods that primarily focus on structural changes, this technique provides detailed insights into how well the lungs are functioning at the molecular level. The unique use of hyperpolarized xenon gas allows for clearer and more precise imaging of the lungs, which could lead to earlier diagnosis and better management of conditions like chronic lung allograft dysfunction (CLAD) in transplant patients. This could potentially improve patient outcomes by allowing for timely interventions.

What evidence suggests that hyperpolarized xenon MRI is effective for assessing lung transplant rejection?

Research shows that hyperpolarized xenon-129 MRI provides detailed images of the lungs. Studies suggest it may detect lung problems earlier and more accurately than traditional methods like spirometry, which measures lung capacity. This trial will use hyperpolarized xenon-129 MRI to assess lung function in various groups, including post-lung transplant patients with and without chronic lung allograft dysfunction (CLAD), non-transplant COPD patients, and healthy control subjects. This imaging technique reveals lung function, especially in lung transplant patients, and can identify changes in lung tissue before issues become serious. Early findings indicate it could help diagnose CLAD, a serious condition in lung transplant patients. Overall, this method offers a clearer view of lung health. ^{1 2 3 6 7}

Who Is on the Research Team?

Maxim Itkin, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 (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]

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 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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04941573

NCT04941573 | Assessment of Chronic Lung Allograft ... This study will use Magnetic Resonance Imaging (MRI) to study the lungs of 90 volunteers using the inhaled contrast agent, hyperpolarized xenon-129.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2950133424000661

Hyperpolarized 129 Xe MRI and spectroscopy of gas ... Those with established allografts (n = 10) underwent 129Xe gas-exchange MRI and spectroscopy and were compared to results from 16 young healthy volunteers and ...

3. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/radiol.230636

Using Functional Lung MRI to Predict Chronic ... This noncontrast, free-breathing MRI method can be used to detect signal modulation based on the change in lung tissue density (ventilation) and vascular ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05550662

HP 129Xe MRI for Evaluation of CLAD in Lung Transplant ... 129Xe-MRI could provide a diagnostic tool that is able to detect CLAD more sensitively and earlier than the current gold standard measurements of spirometry and ...

5. researchgate.net researchgate.net/publication/381275378_Hyperpolarized_129Xe_MRI_and_Spectroscopy_of_Gas-Exchange_Abnormalities_in_Bilateral_Lung_Transplant_Recipients

(PDF) Hyperpolarized 129Xe MRI and Spectroscopy of ... Those with established allografts (n = 10) underwent ¹²⁹Xe gas-exchange MRI and spectroscopy and were compared to results from 16 young healthy volunteers and ...

6. withpower.com withpower.com/trial/phase-1-6-2021-507af

Hyperpolarized Xenon MRI for Lung Transplant Rejection Inhalation of hyperpolarized xenon-129 (129Xe) was found to be safe and well tolerated among 44 subjects, including healthy individuals and patients with ...

7. reporter.nih.gov reporter.nih.gov/project-details/11109637

Predicting the onset of chronic rejection in lung transplant ... Narrative This project seeks to use hyperpolarized xenon-129 MRI to establish a set of imaging markers capable of detecting the early onset of chronic lung ...