Hyperpolarized xenon-129 MRI signatures to detect and manage acute cellular rejection after lung transplant

Advanced Immunoclinical Phenotyping of Rejection in Lung Transplant

We will see if hyperpolarized xenon-129 MRI can detect early acute cellular rejection in recent lung transplant recipients and guide targeted bronchoscopic sampling.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: University of Virginia (Academic / other)
• Locations: 1 site (Charlottesville, Virginia)
• Trial ID: NCT07046910 on ClinicalTrials.gov

What this trial studies

This phase 2 interventional protocol combines hyperpolarized xenon-129 MRI (HGMRI) with anatomic CT and navigational bronchoscopy to map regional physiologic abnormalities in lung allografts. Participants are lung transplant recipients within 12 months post-transplant in the University of Virginia surveillance program who undergo HGMRI, CT fusion, and guided bronchoscopic tissue sampling. Collected tissue will undergo single-cell transcriptomic analysis to compare molecular immune signatures with MRI-derived physiologic patterns. The approach aims to refine imaging signatures that identify ACR earlier than pulmonary function tests or standard chest CT.

Who should consider this trial

Good fit: Ideal candidates are adult lung transplant recipients followed at the University of Virginia within 12 months of transplant who have stable baseline graft function (FEV1 > 45%) and can tolerate outpatient MRI and bronchoscopy.

Not a fit: Patients with significant allograft dysfunction, contraindications to MRI or bronchoscopy, abnormal screening labs, or who are outside the 12-month post-transplant window are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could allow earlier, more precise detection of acute rejection and enable targeted treatment to reduce chronic graft failure.

How similar studies have performed: Preliminary pilot data from this group showed HGMRI can detect regional physiologic abnormalities that correlated with biopsy-proven ACR even when PFTs and CT were normal, but larger validation is still needed.

Eligibility criteria

Inclusion Criteria:

* All subjects must be willing to participate and undergo the procedure, and be managed as outpatients
* HXe MRI-specific Inclusion
* All patients who successfully underwent a lung transplant at the University of Virginia
* Followed by the medical lung transplant team for the post-lung transplant rejection surveillance program at the University of Virginia
* a clinical diagnosis of lung transplant within the past 12 months
* absence of any significant allograft dysfunction/rejection at the time of the 12-month surveillance bronchoscopy
* the ability to understand a written informed consent form and comply with the requirements of the study.
* have an acceptable pre-bronchoscopy pulmonary function test: FEV1\>45% before use of any bronchodilator
* Must have acceptable pre-procedural screening studies.
* Complete Blood Count: normal WBC, Hgb, and PLT
* PT: Normal \< 1.2
* Basic Metabolic Panel: Normal

  1. Scenario 1 (two visits): Standard bronchoscopy with Normal MRI results and without a diagnosis of acute rejection after bronchoscopy.
  2. Scenario 2 (two visits): Navigational bronchoscopy with abnormal MRI result but without a diagnosis of acute rejection after bronchoscopy by clinical pathology.
  3. Scenario 3 (three or four visits): Navigational bronchoscopy with abnormal MRI result and a diagnosis of acute rejection after bronchoscopy by clinical pathology at the first visit, the second visit, or both visits.
  4. Scenario 4 (one visit): Subjects who previously signed Part 2 Substudy corresponding to the First HXe MRI visit of the Part 3 Substudy (6 or 12 month evaluation). They will be asked to join the Part 3 Substudy to undergo a 24-month follow-up evaluation, including MRI and bronchoscopy, as described for Scenarios 1, 2, or 3.

     Exclusion Criteria:

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  1. Unable to Consent
  2. Continuous oxygen use at home.
  3. Blood oxygen saturation of less than 92% as measured by pulse oximetry on the day of imaging.
  4. FEV1 percent predicted less than 25%.
  5. Pregnancy or lactation.
  6. Claustrophobia, inner ear implants, aneurysms or other surgical clips, metal foreign bodies in the eye, pacemakers, or other contraindications to MR scanning. Subjects with any implanted device that cannot be verified as MRI compliant will be excluded.
  7. Chest circumference greater than that of the xenon MR and/or helium coil. The circumference of the coil is approximately 42 inches.
  8. History of congenital cardiac disease, chronic renal failure, or cirrhosis.
  9. Inability to understand simple instructions or to hold still for approximately 10 seconds.
  10. History of respiratory infection within 2 weeks prior to the MR scan
  11. History of MI, stroke, and/or poorly controlled hypertension.
  12. Failure to complete study-related procedures
  13. Unavailability of a reliable communication network and contacts for follow-up with the second in-house backup contact
  14. Patient actively smokes.
  15. Before 48 hours, any event being considered to be too risky to preclude surveillance bronchoscopy: SaO2 \<90%, \>16 puffs/24 hours of short-acting β-agonist (SABA), worsening symptoms prompting the use of any inhalers, FEV1 \< 45% before using a bronchodilator.
  16. acute or chronic renal failure
  17. uncontrolled coronary artery disease or congestive heart failure; uncontrolled diabetes mellitus; uncontrolled hypertension, liver disease; history of neurologic diseases, including stroke, any disease concerning fibrotic processes.
  18. Pregnant females will be excluded
  19. Claustrophobic or too large to fit into the available MR chest RF coils.

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Where this trial is running

Charlottesville, Virginia

• University of Virginia — Charlottesville, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Yun M Shim, MD — University of Virginia
• Study coordinator: Carol Bampoe, BS

Conditions Lung Transplant Rejection; lung transplant; hyperpolarized xenon-129 MRI; bronchoscopy